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Sample records for prevalent hcv genotypes

  1. Prevalence of mixed hepatitis C virus (HCV genotypes among recently diagnosed dialysis patients with HCV infection

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    Mohammed A Al Balwi

    2011-01-01

    Full Text Available Hepatitis C virus (HCV infection is considered a major health problem recognized globally. HCV is a major cause of chronic liver disease that may lead to cirrhosis and hepatocellular carcinoma. The aim of this study was to investigate the prevalence of multiple (mixed HCV genotypes in Saudi patients recently diagnosed with HCV infection and their association with various clinical risk factors. We examined a total of 1,292 newly diagnosed HCV-positive cases between January 2006 and July 2009 at the Molecular Pathology Laboratory, King Abdulaziz Medical City, Riyadh. The clinical and laboratory data of the study patients were collected. The HCV-RNA viral load and its genotyping were carried out with RT-PCR technology to assist in the follow-up and management of HCV-infected patients undergoing antiviral therapy. Twenty-two patients (1.7% were found to have mixed HCV genotypes; of them, mixed genotypes associated with genotype-4 were seen in 19 patients (86%, mixed genotypes associated with genotype-1 were found in 68.4%, with genotype-3 in 26.3% and with genotype-2 in 5.3%. Additionally, mixed genotypes associated with genotype-1 were seen in three cases (13.6%; they were associated with genotype-2 in two (66.7% and with genotype-5 in one patient (33.3%. In conclusion, the prevalence rate of mixed HCV genotypes in the cohort of the newly infected Saudi patients was 1.7%, with genotype-4 being the most frequent genotype encountered.

  2. Active hepatitis C infection and HCV genotypes prevalent among the IDUs of Khyber Pakhtunkhwa

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    Uz Zaman Khaleeq

    2011-06-01

    Full Text Available Abstract Injection drug users (IDUs are considered as a high risk group to develop hepatitis C due to needle sharing. In this study we have examined 200 injection drug users from various regions of the Khyber Pakhtunkhwa province for the prevalence of active HCV infection and HCV genotypes by Immunochromatographic assays, RT-PCR and Type-specific PCR. Our results indicated that 24% of the IDUs were actively infected with HCV while anti HCV was detected among 31.5% cases. Prevalent HCV genotypes were HCV 2a, 3a, 4 and 1a. Majority of the IDUs were married and had attained primary or middle school education. 95% of the IDUs had a previous history of needle sharing. Our study indicates that the rate of active HCV infection among the IDUs is higher with comparatively more prevalence of the rarely found HCV types in KPK. The predominant mode of HCV transmission turned out to be needle sharing among the IDUs.

  3. HIV and HCV coinfection: prevalence, associated factors and genotype characterization in the Midwest Region of Brazil.

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    Freitas, Solange Zacalusni; Teles, Sheila Araújo; Lorenzo, Paulo Cesar; Puga, Marco Antonio Moreira; Tanaka, Tayana Serpa Ortiz; Thomaz, Danilo Yamamoto; Martins, Regina Maria Bringel; Druzian, Angelita Fernandes; Lindenberg, Andréa Siqueira Campos; Torres, Marina Sawada; Pereira, Sérgio A; Villar, Livia Melo; Lampe, Elisabete; Motta-Castro, Ana Rita Coimbra

    2014-01-01

    A cross-sectional study on prevalence, associated factors and genotype distribution of HCV infection was conducted among 848 HIV-infected patients recruited at reference centers in the Midwest Region of Brazil. The prevalence rate of HIV-HCV coinfection was 6.9% (95% CI: 5.2 to 8.6). In multivariable analysis, increasing age, use of illicit drugs (injection and non-injection), a history of blood transfusion before 1994, and the absence of a steady partnership were significant independent associated factors for HIV-HCV coinfection. The phylogenetic analysis based on the NS5B region revealed the presence of two major circulating genotypes of HCV: genotypes 1 (58.3%) and 3 (41.7%). The prevalence of HIV-HCV coinfection was lower than those reported in studies conducted with HIV-infected patients in different regions of Brazil, due to the fact that illicit drug use is not a frequent mode of HIV transmission in this region of Brazil. Serologic screening of HIV-patients for HCV before initiating antiretroviral treatment, a comprehensive identification of associated factors, and the implementation of effective harm reduction programs are highly recommended to provide useful information for treatment and to prevent HCV coinfection in these patients.

  4. HIV AND HCV COINFECTION: PREVALENCE, ASSOCIATED FACTORS AND GENOTYPE CHARACTERIZATION IN THE MIDWEST REGION OF BRAZIL

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    Solange Zacalusni Freitas

    2014-12-01

    Full Text Available A cross-sectional study on prevalence, associated factors and genotype distribution of HCV infection was conducted among 848 HIV-infected patients recruited at reference centers in the Midwest Region of Brazil. The prevalence rate of HIV-HCV coinfection was 6.9% (95% CI: 5.2 to 8.6. In multivariable analysis, increasing age, use of illicit drugs (injection and non-injection, a history of blood transfusion before 1994, and the absence of a steady partnership were significant independent associated factors for HIV-HCV coinfection. The phylogenetic analysis based on the NS5B region revealed the presence of two major circulating genotypes of HCV: genotypes 1 (58.3% and 3 (41.7%. The prevalence of HIV-HCV coinfection was lower than those reported in studies conducted with HIV-infected patients in different regions of Brazil, due to the fact that illicit drug use is not a frequent mode of HIV transmission in this region of Brazil. Serologic screening of HIV-patients for HCV before initiating antiretroviral treatment, a comprehensive identification of associated factors, and the implementation of effective harm reduction programs are highly recommended to provide useful information for treatment and to prevent HCV coinfection in these patients.

  5. Detection of HCV genotypes using molecular and radio-isotopic methods

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    Ahmad, N.; Baig, S.M.; Shah, W.A.; Khattak, K.F.; Khan, B.; Qureshi, J.A.

    2004-01-01

    Hepatitis C virus (HCV) accounts for most cases of acute and chronic non-A and non-B liver diseases. Persistent HCV infection may lead to liver cirrhosis and hepatocellular carcinoma. Six major HCV genotypes have been recognized. Infection with different genotypes results in different clinical pictures and responses to antiviral therapy. In the area of Faisalabad (Punjab province of Pakistan), the prevalence and molecular epidemiology of Hepatitis C virus infection had never been investigated before. In this study, we have made an attempt to determine the prevalence, distribution and clinical significance of HCV infection in 1100 suspected patients of liver disease by nested reverse transcriptase polymerase chain reaction (RTPCR) over a period of four years. HCV genotypes of isolates were determined by dot-blot hybridization with genotype specific radiolabeled probes in 337 subjects. The proportion of patients with HCV genotypes 1,2,3 and 4 were 37.38%, 1.86%, 16.16% and 0.29% respectively. Mixed infection of HCV genotype was detected in 120 (35.6%) patients, whereas 31 (9.1%) samples remained unclassified. This study revealed changing epidemiology of hepatitis C virus genotype 1 and 3 in the patients. Multiple infection of HCV genotype in the same patient may be of great clinical and pathological importance and interest. (author)

  6. Distribution of HCV genotypes among different exposure categories in Brazil

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    Oliveira M.L.A.

    1999-01-01

    Full Text Available Hepatitis C virus (HCV infection is widespread and responsible for more than 60% of chronic hepatitis cases. HCV presents a genetic variability which has led to viral classification into at least 6 genotypes and a series of subtypes. These variants present characteristic geographical distribution, but their association with different responses to treatment with interferon and severity of disease still remains controversial. The aim of this study was to investigate the patterns of distribution of HCV genotypes among different exposure categories in Brazil. Two hundred and fifty anti-HCV positive samples were submitted to HCV-RNA detection by RT-PCR and their genotype was determined by restriction fragment length polymorphism (RFLP analysis. In addition, the genotype/subtype of 60 samples was also determined by a reverse hybridization assay. HCV 1 was the most prevalent (72.0%, followed by type 3 (25.3%, HCV 2 (2.0% and HCV 4 (0.7%. The HCV genotype distribution varied among the different exposure categories, with HCV 1 being more frequent among blood donors, hemophiliacs and hemodialysis patients. A high frequency of HCV 3 was observed in cirrhotic patients, blood donors from the South of Brazil and injecting drug users (IDUs. The general distribution of the HCV genotype in Brazil is similar to that in other regions of the world.

  7. Low prevalence of HCV infection with predominance of genotype 4 among HIV patients living in Libreville, Gabon.

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    Angélique Ndjoyi-Mbiguino

    Full Text Available Gabon is an endemic area for human immunodeficiency virus (HIV and hepatitis C virus (HCV and the risk of co-infection is high.Between November 2015 and April 2016, we conducted retrospective study on HCV infection among people living with HIV/AIDS (PLHA. A total of 491 PLHA were included in this study and tested for the presence of HCV infection. HIV viral loads were obtained using the Generic HIV viral Load® assay and the CD4+ T cells count was performed using BD FACSCount™ CD4 reagents. HCV screening was performed using the MP Diagnostics HCV ELISA 4.0 kit. HCV genotypes were determined by sequence analysis of NS5B and Core regions. The Mann-Whitney test was used to compare the groups. Chi-2 test and Fisher's Exact Test were used to compare prevalence.HCV seroprevalence was 2.9% (14/491, (95% confidence interval (CI:1.4-4.3%. The percentage of HCV viremic patients, defined by the detection of HCV RNA in plasma, was 57% (8/14, representing 1.6% of the total population. HCV seroprevalence and replicative infection were not statistically differ with gender. The percentage of co-infection increased with age. No correlation with CD4+ T cells count and HIV viral load level was registered in this study. Identified HCV strains were predominantly of genotype 4 (87.5% including 4k, 4e, 4g, 4p, 4f and 4c subtypes. Only one strain belonged to genotype 2 (subtype 2q. Analysis of the NS5B region did not reveal the presence of resistance-associated substitutions for sofosbuvir.A systematic screening of hepatitis C is therefore strongly recommended as well as genotyping of HCV strains in order to adapt treatments for the specific case of people living with HIV/AIDS in Central Africa.

  8. Maternal hepatitis C (HCV) infection and Anti-D immunoglobulin therapy: study testing antibodies, RNA and Genotype of HCV in Baghdad.

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    Al-Kubaisy, Waqar; Daud, Suzanna; Al-Kubaisi, Mustafa Waseem; Al-Kubaisi, Omar Waseem; Abdullah, Nik Nairan

    2018-04-30

    Hepatitis C virus (HCV) infection is a serious health problem. It is a major contributor to end-stage liver disease. Worldwide, 1-8% of all pregnant women were infected. Women with viral hepatitis may be at an increased risk of pregnancy complications. There are several obstetrics intervention acts as risk factors, which are specific to women pertaining the HCV infection; anti-D immunoglobulin (Ig) therapy may be one of them. Our objectives were to estimate the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among women with anti-D Ig therapy. A cross sectional study was conducted. A sample of 154 Rhesus negative (Rh - ve) pregnant women regardless of the anti-D Ig therapy was collected. Anti-HCV were tested using third generation enzyme immunoassay (EIA-3) and immunoblot assay (Lia Tek-111), subsequently. In addition, 89 serum samples were subjected to molecular analysis using RT-PCR and DNA enzyme immunoassay (DEIA) method for the detection of HCV-RNA and genotypes. Anti-HCV, and HCV-RNA seroprevalence were significantly higher (17.1, 35.5%) among women with anti-D Ig than their counter group (6.4, 13.16%), p = .038, .018, respectively. Significant direct positive dose response correlation (r = 0.78, p = .005) had been seen between number of anti-D Ig therapy and anti-HCV seropositive rate. Anti-D Ig therapy act as a risk factor (odds ratio (OR) = 3.01, 95%CI: 1.01-8.9) especially from the third dose onward. Women with anti-D Ig therapy were at higher risk (3.6 times more) of positive HCV-RNA (OR =3.6, 95%CI =1.19-10.837). Genotype HCV-1b showed higher prevalent (52.9%) among the recipients of anti-D Ig therapy while genotype HCV-3a (6.6%) was the lowest. Our study showed that Anti-D immunoglobulin therapy acts as a risk factor for acquiring HCV infection. Screening for HCV should be recommended for all recipients of anti-D Ig. Not only HCV antibodies but HCV-RNA detection being recommended for the diagnosis of HCV

  9. HCV infection among Saudi population: high prevalence of genotype 4 and increased viral clearance rate.

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    Ahmed S Abdel-Moneim

    Full Text Available HCV is a major etiological agent of liver disease with a high rate of chronic evolution. The virus possesses 6 genotypes with many subtypes. The rate of spontaneous clearance among HCV infected individuals denotes a genetic determinant factor. The current study was designed in order to estimate the rate of HCV infection and ratio of virus clearance among a group of infected patients in Saudi Arabia from 2008 to 2011. It was additionally designed to determine the genotypes of the HCV in persistently infected patients. HCV seroprevalence was conducted on a total of 15,323 individuals. Seropositive individuals were tested by Cobas AmpliPrep/Cobas TaqMan HCV assay to determine the ratio of persistently infected patients to those who showed spontaneous viral clearance. HCV genotyping on random samples from persistently infected patients were conducted based on the differences in the 5'untranslated region (5'UTR. Anti-HCV antibodies were detected in 7.3% of the totally examined sera. A high percentage of the HCV infected individuals experienced virus clearance (48.4%. HCV genotyping revealed the presence of genotypes 1 and 4, the latter represented 97.6% of the tested strains. Evidences of the widespread of the HCV genotype 4 and a high rate of HCV virus clearance were found in Saudi Arabia.

  10. Prevalence of Hepatitis C Virus Subgenotypes 1a and 1b in Japanese Patients: Ultra-Deep Sequencing Analysis of HCV NS5B Genotype-Specific Region

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    Wu, Shuang; Kanda, Tatsuo; Nakamoto, Shingo; Jiang, Xia; Miyamura, Tatsuo; Nakatani, Sueli M.; Ono, Suzane Kioko; Takahashi-Nakaguchi, Azusa; Gonoi, Tohru; Yokosuka, Osamu

    2013-01-01

    Background Hepatitis C virus (HCV) subgenotypes 1a and 1b have different impacts on the treatment response to peginterferon plus ribavirin with direct-acting antivirals (DAAs) against patients infected with HCV genotype 1, as the emergence rates of resistance mutations are different between these two subgenotypes. In Japan, almost all of HCV genotype 1 belongs to subgenotype 1b. Methods and Findings To determine HCV subgenotype 1a or 1b in Japanese patients infected with HCV genotype 1, real-time PCR-based method and Sanger method were used for the HCV NS5B region. HCV subgenotypes were determined in 90% by real-time PCR-based method. We also analyzed the specific probe regions for HCV subgenotypes 1a and 1b using ultra-deep sequencing, and uncovered mutations that could not be revealed using direct-sequencing by Sanger method. We estimated the prevalence of HCV subgenotype 1a as 1.2-2.5% of HCV genotype 1 patients in Japan. Conclusions Although real-time PCR-based HCV subgenotyping method seems fair for differentiating HCV subgenotypes 1a and 1b, it may not be sufficient for clinical practice. Ultra-deep sequencing is useful for revealing the resistant strain(s) of HCV before DAA treatment as well as mixed infection with different genotypes or subgenotypes of HCV. PMID:24069214

  11. Evaluation of the Abbott Real Time HCV genotype II assay for Hepatitis C virus genotyping.

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    Sariguzel, Fatma Mutlu; Berk, Elife; Gokahmetoglu, Selma; Ercal, Baris Derya; Celik, Ilhami

    2015-01-01

    The determination of HCV genotypes and subtypes is very important for the selection of antiviral therapy and epidemiological studies. The aim of this study was to evaluate the performance of Abbott Real Time HCV Genotype II assay in HCV genotyping of HCV infected patients in Kayseri, Turkey. One hundred patients with chronic hepatitis C admitted to our hospital were evaluated between June 2012 and December 2012, HCV RNA levels were determined by the COBAS® AmpliPrep/COBAS® TaqMan® 48 HCV test. HCV genotyping was investigated by the Abbott Real Time HCV Genotype II assay. With the exception of genotype 1, subtypes of HCV genotypes could not be determined by Abbott assay. Sequencing analysis was used as the reference method. Genotypes 1, 2, 3 and 4 were observed in 70, 4, 2 and 24 of the 100 patients, respectively, by two methods. The concordance between the two systems to determine HCV major genotypes was 100%. Of 70 patients with genotype 1, 66 showed infection with subtype 1b and 4 with subtype 1a by Abbott Real Time HCV Genotype II assay. Using sequence analysis, 61 showed infection with subtype 1b and 9 with subtype 1a. In determining of HCV genotype 1 subtypes, the difference between the two methods was not statistically significant (P>0.05). HCV genotype 4 and 3 samples were found to be subtype 4d and 3a, respectively, by sequence analysis. There were four patients with genotype 2. Sequence analysis revealed that two of these patients had type 2a and the other two had type 2b. The Abbott Real Time HCV Genotype II assay yielded results consistent with sequence analysis. However, further optimization of the Abbott Real Time HCV Genotype II assay for subtype identification of HCV is required.

  12. Comparison of cobas HCV GT against Versant HCV Genotype 2.0 (LiPA) with confirmation by Sanger sequencing.

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    Yusrina, Falah; Chua, Cui Wen; Lee, Chun Kiat; Chiu, Lily; Png, Tracy Si-Yu; Khoo, Mui Joo; Yan, Gabriel; Lee, Guan Huei; Yan, Benedict; Lee, Hong Kai

    2018-05-01

    Correct identification of infecting hepatitis C virus (HCV) genotype is helpful for targeted antiviral therapy. Here, we compared the HCV genotyping performance of the cobas HCV GT assay against the Versant HCV Genotype 2.0 (LiPA) assay, using 97 archived serum samples. In the event of discrepant or indeterminate results produced by either assay, the core and NS5B regions were sequenced. Of the 97 samples tested by the cobas, 25 (26%) were deemed indeterminate. Sequencing analyses confirmed 21 (84%) of the 25 samples as genotype 6 viruses with either subtype 6m, 6n, 6v, 6xa, or unknown subtype. Of the 97 samples tested by the LiPA, thirteen (13%) were deemed indeterminate. Seven (7%) were assigned with genotype 1, with unavailable/inconclusive results from the core region of the LiPA. Notably, the 7 samples were later found to be either genotype 3 or 6 by sequencing analyses. Moreover, 1 sample by the LiPA was assigned as genotypes 4 (cobas: indeterminate) but were later found to be genotype 3 by sequencing analyses, highlighting its limitation in assigning the correct genotype. The cobas showed similar or slightly higher accuracy (100%; 95% CI 94-100%) compared to the LiPA (99%; 95% CI 92-100%). Twenty-six percent of the 97 samples tested by the cobas had indeterminate results, mainly due to its limitation in identifying genotype 6 other than subtypes 6a and 6b. This presents a significant assay limitation in Southeast Asia, where genotype 6 infection is highly prevalent. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. NAFLD and NASH in HCV Infection: Prevalence and Significance in Hepatic and Extrahepatic Manifestations

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    Luigi Elio Adinolfi

    2016-05-01

    Full Text Available The aim of this paper is to review and up to date the prevalence of hepatitis C virus (HCV-associated non-alcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH and their significance in both accelerating progression of HCV-related liver disease and development of HCV-associated extrahepatic diseases. The reported mean prevalence of HCV-related NAFLD was 55%, whereas NASH was reported in 4%–10% of cases. HCV genotype 3 directly induces fatty liver deposition, namely “viral steatosis” and it is associated with the highest prevalence and degree of severity, whereas, HCV non-3 genotype infection showed lower prevalence of steatosis, which is associated with metabolic factors and insulin resistance. The host’s genetic background predisposes him or her to the development of steatosis. HCV’s impairment of lipid and glucose metabolism causes fatty liver accumulation; this seems to be a viral strategy to optimize its life cycle. Irrespective of insulin resistance, HCV-associated NAFLD, in a degree-dependent manner, contributes towards accelerating the liver fibrosis progression and development of hepatocellular carcinoma by inducing liver inflammation and oxidative stress. Furthermore, NAFLD is associated with the presence of metabolic syndrome, type 2 diabetes, and atherosclerosis. In addition, HCV-related “metabolic steatosis” impairs the response rate to interferon-based treatment, whereas it seems that “viral steatosis” may harm the response rate to new oral direct antiviral agents. In conclusion, a high prevalence of NAFLD occurs in HCV infections, which is, at least in part, induced by the virus, and that NAFLD significantly impacts progression of the liver disease, therapeutic response, and some extrahepatic diseases.

  14. Hepatitis C virus (HCV genotype 1 subtype identification in new HCV drug development and future clinical practice.

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    Stéphane Chevaliez

    Full Text Available BACKGROUND: With the development of new specific inhibitors of hepatitis C virus (HCV enzymes and functions that may yield different antiviral responses and resistance profiles according to the HCV subtype, correct HCV genotype 1 subtype identification is mandatory in clinical trials for stratification and interpretation purposes and will likely become necessary in future clinical practice. The goal of this study was to identify the appropriate molecular tool(s for accurate HCV genotype 1 subtype determination. METHODOLOGY/PRINCIPAL FINDINGS: A large cohort of 500 treatment-naïve patients eligible for HCV drug trials and infected with either subtype 1a or 1b was studied. Methods based on the sole analysis of the 5' non-coding region (5'NCR by sequence analysis or reverse hybridization failed to correctly identify HCV subtype 1a in 22.8%-29.5% of cases, and HCV subtype 1b in 9.5%-8.7% of cases. Natural polymorphisms at positions 107, 204 and/or 243 were responsible for mis-subtyping with these methods. A real-time PCR method using genotype- and subtype-specific primers and probes located in both the 5'NCR and the NS5B-coding region failed to correctly identify HCV genotype 1 subtype in approximately 10% of cases. The second-generation line probe assay, a reverse hybridization assay that uses probes targeting both the 5'NCR and core-coding region, correctly identified HCV subtypes 1a and 1b in more than 99% of cases. CONCLUSIONS/SIGNIFICANCE: In the context of new HCV drug development, HCV genotyping methods based on the exclusive analysis of the 5'NCR should be avoided. The second-generation line probe assay is currently the best commercial assay for determination of HCV genotype 1 subtypes 1a and 1b in clinical trials and practice.

  15. Impact of inter-genotypic recombination and probe cross-reactivity on the performance of the Abbott RealTime HCV Genotype II assay for hepatitis C genotyping.

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    Sridhar, Siddharth; Yip, Cyril C Y; Chan, Jasper F W; To, Kelvin K W; Cheng, Vincent C C; Yuen, Kwok-Yung

    2018-05-01

    The Abbott RealTime HCV Genotype II assay (Abbott-RT-HCV assay) is a real-time PCR based genotyping method for hepatitis C virus (HCV). This study measured the impact of inter-genotypic recombination and probe cross-reactivity on the performance of the Abbott-RT-HCV assay. 517 samples were genotyped using the Abbott-RT-HCV assay over a one-year period, 34 (6.6%) were identified as HCV genotype 1 without further subtype designation raising the possibility of inaccurate genotyping. These samples were subjected to confirmatory sequencing. 27 of these 34 (79%) samples were genotype 1b while five (15%) were genotype 6. One HCV isolate was an inter-genotypic 1a/4o recombinant. This is a novel natural HCV recombinant that has never been reported. Inter-genotypic recombination and probe cross-reactivity can affect the accuracy of the Abbott-RT-HCV assay, both of which have significant implications on antiviral regimen choice. Confirmatory sequencing of ambiguous results is crucial for accurate genotyping. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. The relationships between IFNL4 genotype, intrahepatic interferon-stimulated gene expression and interferon treatment response differs in HCV-1 compared with HCV-3.

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    Holmes, J A; Congiu, M; Bonanzinga, S; Sandhu, M K; Kia, Y H; Bell, S J; Nguyen, T; Iser, D M; Visvanathan, K; Sievert, W; Bowden, D S; Desmond, P V; Thompson, A J

    2015-08-01

    The biological mechanism underlying the association between IFNL4/IFNL3 polymorphism and peginterferon/ribavirin (PR) response in HCV-1 is thought to involve differential intrahepatic interferon-stimulated gene expression. HCV-3 is more sensitive to PR, but there are no studies of the association between IFNL4 polymorphism, PR treatment response and liver interferon-stimulated gene expression in HCV-3. We evaluated the association between IFNL4/IFNL3 genotypes, PR treatment outcomes and intrahepatic interferon-stimulated gene expression, according to HCV genotype. HCV-1 and HCV-3 patients who received PR therapy were identified. IFNL3 (rs12979860) and IFNL4 genotype (rs368234815) were determined. A second cohort with stored liver specimens was identified. Expression of ISGs was measured by rt-PCR. Two hundred and fifty-nine patients were identified: 55% HCV-1, 45% HCV-3. IFNL4 genotype frequency was TT/TT 44%, TT/ΔG 42% andΔG/ΔG 14%. Linkage disequilibrium with IFNL3 genotype was high (r(2) = 0.98). The association between IFNL4 genotype and PR response was attenuated in HCV-3 vs. HCV-1 (HCV-3: SVR 89% vs. 76% vs. 72% for TT/TT vs. TT/ΔG vs. ΔG/ΔG, P = 0.09; HCV-1: SVR: 82% vs. 29% vs. 24%, P < 0.001). Intrahepatic ISG expression was evaluated in 92 patients; 61% HCV-1. The association between IFNL4 genotype and liver ISG expression was significantly different for HCV-3 vs. HCV-1 (P-value for interaction = 0.046), with levels of interferon-stimulated gene expression being highest in HCV-1 patients who carried a poor-response IFNL4 genotype. The relationship between IFNL4 genotype and PR treatment response as well as intrahepatic interferon-stimulated gene expression differs between HCV-1 and HCV-3. These data suggest fundamental differences in host-virus interactions according to HCV genotype. © 2015 John Wiley & Sons Ltd.

  17. [Prevalence and genotype distribution changes in hepatitis C virus co-infection among human immunodeficiency virus-infected patients].

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    Cifuentes, Celia; Mancebo-Hernández, María; Pérez-Navarro, Elisabet; Recio, Eva; Monje-Agudo, Patricia; Valiente, Adoración; Pineda, Juan A

    2015-02-01

    The prevalence of hepatitisC is decreasing among new diagnoses of HIV/HCV coinfection in Spain. The increasing use of the HCV treatment could have changed the HCV genotype distribution. The aim of this study is to analyze changes in the prevalence of HCV coinfection and in HCV genotype distribution among HIV-infected patients. A serial cross-sectional study was conducted that included all HIV-infected patients who attended the Outpatient Clinic of a hospital in Andalusia, between September 2008 and February 2009 (first period), and between January 2013 and June 2013 (second period). A total of 520 and 651 patients were included in the first and second period, respectively. The risk factors of HCV infection in the first vs. second period were: IDU, 319 (61%) vs. 348 (53%); heterosexual contact, 111 (21%) vs. 135 (21%); homosexual men, 76 (15%) vs. 114 (22%) (P=.006). The prevalence of HCV antibody per period was: 358 (69%) vs. 380 (58%) (P=<.001), and for the HCV-RNA was 255 (49%) vs. 240 (37%) (P=<.001). In both periods, the HCV genotype distribution was: 1, 137 (60%) vs. 138 (59%); 3, 45 (20%) vs. 42 (18%); 4, 42 (18%) vs. 47 (20%) (P=.881). The prevalence of HCV infection in HIV-infected patients has decreased in our area, including overall exposure to HCV virus and active infection during the last 5 years. However, the HCV genotype distribution has not changed. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  18. Spontaneous viral clearance, viral load, and genotype distribution of hepatitis C virus (HCV) in HIV-infected patients with anti-HCV antibodies in Europe

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    Soriano, Vincent; Mocroft, Amanda; Rockstroh, Juergen

    2008-01-01

    BACKGROUND: Variables influencing serum hepatitis C virus (HCV) RNA levels and genotype distribution in individuals with human immunodeficiency virus (HIV) infection are not well known, nor are factors determining spontaneous clearance after exposure to HCV in this population. METHODS: All HCV...... for hepatitis B surface antigen (HBsAg) were more likely to have spontaneously cleared HCV than were those negative for HBsAg (43% vs. 21%; aOR, 2.91 [95% CI, 1.94-4.38]). Of patients with HCV viremia, 786 (53%) carried HCV genotype 1, and 53 (4%), 440 (29%), and 217 (15%) carried HCV genotype 2, 3, and 4...

  19. Prevalence and Genotypic Distribution of Hepatitis C Virus in Peshawar KPK, Pakistan

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    Tanweer Kumar

    2017-01-01

    Full Text Available This present study was planned to obtain an up-to-date picture of Hepatitis C virus (HCV infection and its genotypes distribution in Peshawar, Khyber Pakhtunkhwa, Pakistan, as well as of the relationship between HCV genotypes and demographic and clinical parameters, and the risk factors in patients with an HCV subtype. Samples (blood from 1978 individuals were collected and were tested using a strip-based method called the immunochromatographic test (ICT for the existence of antibodies against HCV. It was observed that 158 of the 1978 individuals (7.9% harbored antibodies in their blood against HCV, among which the female percentage (53.2% was higher than that of the male (46.8%. Among the different age groups, the highest number of incidences of HCV antibodies was found in the age group of 31–40 years (26.6%. ICT positive samples were further screened by polymerase chain reaction (PCR to determine the existence of active HCV-RNA, and it was found that 6.21% (123 of the total population (1978 tested, was positive, among which the female rate (56.91% was observed to be higher than that of the male (43.09%. The highest incidence recorded was in the age group of 41–50 years (33.3%. HCV RNA positive individuals were genotyped: genotype 3a (45.5% was dominant among the other detected genotypes, followed by 1a (11.4%, 3b (4.9%, and 2a (4.1%. It was concluded that the highest prevalence of HCV was found in females, and that the dominant genotype of the screened individuals was 3a genotype.

  20. Hepatitis C virus genotypes in Myanmar.

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    Win, Nan Nwe; Kanda, Tatsuo; Nakamoto, Shingo; Yokosuka, Osamu; Shirasawa, Hiroshi

    2016-07-21

    Myanmar is adjacent to India, Bangladesh, Thailand, Laos and China. In Myanmar, the prevalence of hepatitis C virus (HCV) infection is 2%, and HCV infection accounts for 25% of hepatocellular carcinoma. In this study, we reviewed the prevalence of HCV genotypes in Myanmar. HCV genotypes 1, 3 and 6 were observed in volunteer blood donors in and around the Myanmar city of Yangon. Although there are several reports of HCV genotype 6 and its variants in Myanmar, the distribution of the HCV genotypes has not been well documented in areas other than Yangon. Previous studies showed that treatment with peginterferon and a weight-based dose of ribavirin for 24 or 48 wk could lead to an 80%-100% sustained virological response (SVR) rates in Myanmar. Current interferon-free treatments could lead to higher SVR rates (90%-95%) in patients infected with almost all HCV genotypes other than HCV genotype 3. In an era of heavy reliance on direct-acting antivirals against HCV, there is an increasing need to measure HCV genotypes, and this need will also increase specifically in Myanmar. Current available information of HCV genotypes were mostly from Yangon and other countries than Myanmar. The prevalence of HCV genotypes in Myanmar should be determined.

  1. Hepatitis C virus genotyping of organ donor samples to aid in transplantation of HCV-positive organs.

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    Gentile, Caren; Van Deerlin, Vivianna M; Goldberg, David S; Reese, Peter P; Hasz, Richard D; Abt, Peter; Blumberg, Emily; Farooqi, Midhat S

    2018-02-01

    Given the availability of new highly efficacious anti-HCV therapies, some clinicians have advocated for wider use of kidneys from hepatitis C virus-positive (HCV+) donors, including transplanting them into HCV-negative recipients. As treatment regimens for HCV are commonly guided by genotype, pretransplant HCV genotyping of tissue donors would be beneficial. To our knowledge, donor HCV genotyping has never been reported. We retrieved archived frozen plasma samples for 17 previous organ donors through a local organ procurement organization. We performed HCV genotyping using the eSensor HCVg Direct Test (GenMark Diagnostics) and also by Sanger sequencing, for confirmation (Retrogen). In addition, viral loads were measured using the COBAS AmpliPrep/TaqMan system (Roche Diagnostics). We found that most of the samples (n = 14) were HCV Genotype 1a with the remainder being Genotype 2b (n = 1) or Genotype 3 (n = 2). All genotyping results were concordant with Sanger sequencing. The average HCV viral load in the sample group was ~ 1.6 million IU/mL (range: ~16 000 IU/mL to 7 million IU/mL). We demonstrate that viral RNA from organ donor plasma can be successfully genotyped for HCV. This ability suggests that transplantation of HCV+ kidneys into HCV-negative recipients, followed by genotype-guided antiviral therapy, could be feasible. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. The prevalence of autoantibody and its relationship with genotypes of hepatitis C virus in patients with chronic hepatitis C virus infection.

    Science.gov (United States)

    Kirdar, Sevİn; Sener, Asli Gamze; Cengİz, Merve; Aydin, Nerİman

    2016-11-01

    The prevalence of autoantibody in the patients with chronic hepatitis C infection, and the relationship between the autoantibodies and HCV genotypes were investigated in this study. One hundred and eight anti-HCV positive and 86 anti-HCV negative patients were included in the study. Anti-HCV were studied by enzyme immunassay (EIA). HCV RNA was determined by real time polymerase chain reaction (PCR) and HCV genotypes were determined by a reverse-line blot hybridization. Anti-nuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA), Anti-mitochondrial antibodies (AMA), liver kidney microsomal antibodies (LKM) were detected by indirect immunofluorescence assay. Among patients, 13 (12.03%) of 108 were positive for at least one autoantibody. The positivity was not observed in control group. The most prevalent autoantibody in anti-HCV positive group was ANA. ANA was positive in six HCV patients with genotype 1. In HCV patients with genotype 1, the frequencies of ANA, ASMA, AMA and LKM1 were six, two, three and one, respectively. In HCV patients with genotype 2, ANA was positive one patient and ASMA, AMA and LKM1 were not detected in HCV patients with genotype 2. In conclusion, the autoantibodies in patients with chronic hepatitis C in the study were low as compared to those reported in previous studies. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  3. Utility of the Abbott RealTime HCV Genotype Plus RUO assay used in combination with the Abbott RealTime HCV Genotype II assay.

    Science.gov (United States)

    He, Chao; Germer, Jeffrey J; Ptacek, Elizabeth R; Bommersbach, Carl E; Mitchell, P Shawn; Yao, Joseph D C

    Hepatitis virus C (HCV) genotype (GT) determination and subtype (ST) differentiation (1a versus 1b) remain important for the selection of appropriate direct-acting antiviral (DAA) therapy. This study is a retrospective comparison of HCV GT and ST result distribution when using the Abbott RealTime HCV Genotype II assay (HCVGT II) alone and in combination with the Abbott RealTime HCV Genotype Plus RUO assay (HCVGT Plus) for routine testing of clinical serum specimens at a reference laboratory. HCVGT II results of specimens tested from June 2014 through January 2016 (period 1) were compared with combined results from HCVGT II and HCVGT Plus (HCVGT II/Plus) performed from January 2016 through January 2017 (period 2). A total of 44,127 and 25,361 specimens were tested during periods 1 and 2, respectively. Use of HCVGT II/Plus significantly reduced the frequency of GT 1 results without ST (0.4%) when compared to preliminary HCVGT II results during period 2 (5.3%; p < 0.01) and final HCVGT II results in period 1 (5.5%; p < 0.01). HCVGT II/Plus also resulted in GT 6 reactivity in 38 specimens with results of "HCV detected" (n = 17) or GT 1 (n = 21) following initial HCVGT II testing during period 2. When compared to the use of HCVGT II alone, HCVGT II/Plus significantly reduced the frequency of GT 1 without ST results observed in a large reference laboratory, while also enabling the identification of HCV GT 6. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. High prevalence of Hepatitis C virus genotype 6 in Vietnam.

    Science.gov (United States)

    Pham, Duc Anh; Leuangwutiwong, Pornsawan; Jittmittraphap, Akanitt; Luplertlop, Nattanej; Bach, Hoa Khanh; Akkarathamrongsin, Srunthron; Theamboonlers, Apiradee; Poovorawan, Yong

    2009-01-01

    This study aimed to update the prevalence of the various Hepatitis C virus genotypes in Vietnamese blood donors. One hundred and three HCV antibody-positive plasma samples were collected from blood donors at the National Institute of Hematology and Blood Transfusion, Hanoi, Vietnam. All specimens were subjected to RT-PCR of the 5' untranslated region (UTR) to confirm the presence of HCV RNA. The core and NS5B regions of thh positive samples were subsequently amplified by RT-PCR followed by direct sequencing and phylogenetic analysis. Seventy out of 103 samples (68.0%) were RNA positive. Core and NS5B were successfully amplified and sequences were obtained for 70 and 65 samples, respectively. Phylogenetic analysis revealed that genotype 6a was the most predominant among Vietnamese blood donors with a prevalence of 37.1% (26/70), followed by genotype 1a at 30.0% (21/70) and genotype 1b at 17.1% (12/70). The prevalence of two other genotype 6 variants, 6e and 61 was 8.6% and 1.4%, respectively. Further analysis of recent studies showed that the geographic distribution of genotype 6 covered mainly southern China and the mainland of Southeast Asia including Vietnam, Laos, Thailand, and Myanmar. The GenBank accession numbers for the sequences reported in this study are FJ768772-FJ768906.

  5. Prevalence, genotype distribution, and risk factors for hepatitis C infection among HIV-infected individuals in Slovenia: a 1986-2013 update.

    Science.gov (United States)

    Škamperle, Mateja; Seme, Katja; Lunar, Maja M; Maver, Polona J; Tomažič, Janez; Vovko, Tomaž D; Pečavar, Blaž; Matičič, Mojca; Poljak, Mario

    2014-01-01

    Since the introduction of highly active antiretroviral therapy, chronic hepatitis C has become one of the leading causes of non-AIDS-related morbidity and mortality in patients with HIV infection. Two previous Slovenian nationwide studies published in 2002 and 2009 showed a very low prevalence of hepatitis C virus (HCV) infection among Slovenian HIV-infected individuals (14.5% and 10.7%, respectively). The presence of HCV infection was tested in 579/639 (90.6%) patients that were confirmed as HIV-positive in Slovenia by the end of 2013. Among them, 7.6% (44/579) of HIV-infected individuals were anti-HCV-positive, and 33/44 (75%) anti-HCV-positive patients were also HCV RNA-positive. HCV genotype 1 was most prevalent among HIV-infected patients (68%), followed by genotype 3 (20%), genotype 4 (8%), and genotype 2 (4%). Anti-HCV positivity was significantly higher in those that acquired HIV by the parenteral route (91.8%) than in those that acquired HIV by the sexual route (2.8%). Slovenia remains among the countries with the lowest prevalence of HCV infection in HIV-infected individuals. Because the burden of HIV among men who have sex with men in Slovenia is disproportionately high and increasing rapidly, the current favorable situation could change quickly and should be therefore monitored regularly.

  6. PNPLA 3 I148M genetic variant associates with insulin resistance and baseline viral load in HCV genotype 2 but not in genotype 3 infection

    DEFF Research Database (Denmark)

    Rembeck, Karolina; Maglio, Cristina; Lagging, Martin

    2012-01-01

    ABSTRACT: BACKGROUND: Hepatic steatosis in HCV patients has been postulated as a risk factor associated with a higher frequency of fibrosis and cirrhosis. A single genetic variant, PNPLA3 I148M, has been widely associated with increased hepatic steatosis. Previous studies of the PNPLA3 I148M...... sequence variant in HCV infected individuals have reported an association between this variant and prevalence of steatosis, fibrosis, and cirrhosis. To evaluate the impact of PNPLA3 I148M variant on metabolic traits and treatment response in HCV genotype 2 and 3 infected patients. METHODS: Three hundred...

  7. Study of Various HCV Genotypes in Patients Managing by Referral Clinic in Yazd Province

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    M Pedarzadeh

    2012-02-01

    Full Text Available Introduction: Determining virus genotype is a major factor for initiation of treatment because various kinds of genotypes need different antiviral drugs. Distribution of hepatitis C genotype in the word is variable in each country or even in each province. So we need to determine distribution pattern of hepatitis C genotype in our region. This study was performed in referral clinic of Yazd province. Methods: This was a descriptive study conducted between 2007 and 2010 on patients who were observed by Yazd referral clinic (the clinic for evaluating and management of patients with high risk behaviors. Ninety two patients who had positive RIBA test for hepatitis C infection were randomly selected and entered the study. Genotyping was performed using RT-PCR method. The primer was "universal primer HCV". Prevalence of various genotypes was analyzed according to gender, addiction and co- existence of HCV-HIV infection. Personal information and laboratory results were analyzed using SPSS. Results: The most common genotype in our study was genotype 3a (65% of cases, followed by 1a (35%. Globally 83% of patients were IV drug addict. Genotype distribution in these patients was similar to others. Fifteen patients had co-infection of HCV-HIV, and 47% of them were contaminated by genotype 1a and 53% with 3a. We could not find any patient contaminated with genotypes 2 or 4. No other genotypes except 1 & 3 or mixed genotype infection could be determined in our patients. Twenty three percent of patients had negative PCR despite positive RIBA test. This indicates that self improvement from acute hepatitis C infection in IV drug addict patients is similar to other people. Conclusion: According to the results of our study, about 2/3 of patients were infected by genotype 3a. This kind of chronic hepatitis C shows a better response to treatment comparing genotype 1a (or 1b with shorter duration and lower cost drugs. But despite higher incidence of genotype 3a, we

  8. High prevalence of human parvovirus 4 infection in HBV and HCV infected individuals in shanghai.

    Science.gov (United States)

    Yu, Xuelian; Zhang, Jing; Hong, Liang; Wang, Jiayu; Yuan, Zhengan; Zhang, Xi; Ghildyal, Reena

    2012-01-01

    Human parvovirus 4 (PARV4) has been detected in blood and diverse tissues samples from HIV/AIDS patients who are injecting drug users. Although B19 virus, the best characterized human parvovirus, has been shown to co-infect patients with hepatitis B or hepatitis C virus (HBV, HCV) infection, the association of PARV4 with HBV or HCV infections is still unknown.The aim of this study was to characterise the association of viruses belonging to PARV4 genotype 1 and 2 with chronic HBV and HCV infection in Shanghai.Serum samples of healthy controls, HCV infected subjects and HBV infected subjects were retrieved from Shanghai Center for Disease Control and Prevention (SCDC) Sample Bank. Parvovirus-specific nested-PCR was performed and results confirmed by sequencing. Sequences were compared with reference sequences obtained from Genbank to derive phylogeny trees.The frequency of parvovirus molecular detection was 16-22%, 33% and 41% in healthy controls, HCV infected and HBV infected subjects respectively, with PARV4 being the only parvovirus detected. HCV infected and HBV infected subjects had a significantly higher PARV4 prevalence than the healthy population. No statistical difference was found in PARV4 prevalence between HBV or HCV infected subjects. PARV4 sequence divergence within study groups was similar in healthy subjects, HBV or HCV infected subjects.Our data clearly demonstrate that PARV4 infection is strongly associated with HCV and HBV infection in Shanghai but may not cause increased disease severity.

  9. A new HCV genotype 6 subtype designated 6v was confirmed with three complete genome sequences.

    Science.gov (United States)

    Wang, Yizhong; Xia, Xueshan; Li, Chunhua; Maneekarn, Niwat; Xia, Wenjie; Zhao, Wenhua; Feng, Yue; Kung, Hsiang Fu; Fu, Yongshui; Lu, Ling

    2009-03-01

    Although hepatitis C virus (HCV) genotype 6 is classified into 21 subtypes, 6a-6u, new variants continue to be identified. To characterize the full-length genomes of three novel HCV genotype 6 variants: KMN02, KM046 and KM181. From sera of patients with HCV infection, the entire HCV genome was amplified by RT-PCR followed by direct DNA sequencing and phylogenetic analysis. The sera contained HCV genomes of 9461, 9429, and 9461nt in length, and each harboured a single ORF of 9051nt. The genomes showed 95.3-98.1% nucleotide similarity to each other and 72.2-75.4% similarity to 23 genotype 6 reference sequences, which represent subtypes 6a-6u and unassigned variants km41 and gz52557. Phylogenetic analyses demonstrated that they were genotype 6, but were subtypically distinct. Based on the current criteria of HCV classification, they were designed to represent a new subtype, 6v. Analysis of E1 and NS5B region partial sequences revealed two additional related variants, CMBD-14 and CMBD-86 that had been previously reported in northern Thailand and sequences dropped into Genbank. Three novel HCV genotype 6 variants were entirely sequenced and designated subtype 6v.

  10. Differences in HCV viral decline between low and standard-dose pegylated-interferon-alpha-2a with ribavirin in HIV/HCV genotype 3 patients.

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    Antonio Rivero-Juárez

    Full Text Available BACKGROUND: The aim of the study was to analyze the different impact of standard and low-dose Peg-IFN-α2a/RBV therapies on HCV viral decline in HIV/HCV genotype 3 co-infected patients during the first weeks of treatment. METHODS: Plasma HCV viral decline was analyzed between baseline and weeks 1, 2 and 4 in two groups of treatment-naïve HCV genotype 3 patients with HIV co-infection. The Standard Dose Group (SDG included patients who received Peg-IFN at 180 µg/per week with a weight-adjusted dose of ribavirin; Low-Dose Group (LDG patients received Peg-IFN at 135 µg/per week with 800 mg/day ribavirin. The effect of IL28B genotype on HCV viral decline was evaluated in both groups. HCV viral decline was analyzed using a multivariate linear regression model. RESULTS: One hundred and six patients were included: 48 patients in the SDG and 58 in the LDG. HCV viral decline for patients in the LDG was less than for those in the SDG (week 1:1.72±0.74 log(10 IU/mL versus 1.78±0.67 log(10 IU/mL, p = 0.827; week 2:2.3±0.89 log(10 IU/mL versus 3.01±1.02 log(10 IU/mL, p = 0.013; week 4:3.52±1.2 log(10 IU/mL versus 4.09±1.1 log(10 IU/mL, p = 0.005. The linear regression model identified the Peg-IFN/RBV dose as an independent factor for HCV viral decline at week 4. CONCLUSIONS: Our results showed that HCV viral decline was less for patients in the low-dose group compared to those receiving the standard dose. Until a randomized clinical trial is conducted, clinicians should be cautious about using lower doses of Peg-IFN/RBV in HIV/HCV genotype 3 co-infected patients.

  11. Natural Polymorphisms Conferring Resistance to HCV Protease and Polymerase Inhibitors in Treatment-Naïve HIV/HCV Co-Infected Patients in China.

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    Kali Zhou

    Full Text Available The advent of direct-acting agents (DAAs has improved treatment of HCV in HIV co-infection, but may be limited by primary drug resistance. This study reports the prevalence of natural polymorphisms conferring resistance to NS3/4A protease inhibitors and NS5B polymerase inhibitors in treatment-naïve HIV/HCV co-infected individuals in China.Population based NS3/4A sequencing was completed for 778 treatment-naïve HIV/HCV co-infected patients from twelve provinces. NS3 sequences were amplified by nested PCR using in-house primers for genotypes 1-6. NS5B sequencing was completed for genotyping in 350 sequences. Resistance-associated variants (RAVs were identified in positions associated with HCV resistance.Overall, 72.8% (566/778 of all HCV sequences had at least one RAV associated with HCV NS3/4A protease inhibitor resistance. Variants were found in 3.6% (7/193 of genotype 1, 100% (23/23 of genotype 2, 100% (237/237 of genotype 3 and 92% (299/325 of genotype 6 sequences. The Q80K variant was present in 98.4% of genotype 6a sequences. High-level RAVs were rare, occurring in only 0.8% of patients. 93% (64/69 patients with genotype 1b also carried the C316N variant associated with NS5B low-level resistance.The low frequency of high-level RAVs associated with primary HCV DAA resistance among all genotypes in HIV/HCV co-infected patients is encouraging. Further phenotypic studies and clinical research are needed.

  12. Molecular Epidemiology of Hepatitis C Virus (HCV) in Kadun State ...

    African Journals Online (AJOL)

    Hepatitis C virus genotype 1b was found in the entire HCV RNA positive sample. Conclusions: The findings of 6.2% prevalence of HCV infection based on HCV RNA test confirmed that there is Hepatitis C virus in ... HOW TO USE AJOL.

  13. Molecular epidemiology of HCV monoinfection and HIV/HCV coinfection in injection drug users in Liuzhou, Southern China.

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    Yi Tan

    Full Text Available BACKGROUND: Hepatitis C virus (HCV mono-infection and HCV/HIV (human immunodeficiency virus co-infection are growing problems in injection drug users (IDU. Their prevalence and genotypic patterns vary with geographic locations. Access to harm reduction measures is opening up opportunities for improving the HIV/HCV profiling of IDU in China, where IDUs account for a significant proportion of the two infections especially in the southern part of the country. METHODOLOGY/PRINCIPAL FINDINGS: A cross sectional study was conducted. Through the Liuzhou Methadone Clinic, a total of 117 injection drug users (IDUs were recruited from Guangxi, Southern China. A majority of the IDUs (96% were HCV antibody positive, of which 21% were HIV infected. Unlike HCV monoinfection, there was spatial heterogeneity in the distribution of HIV/HCV coinfection, the latter also characterized by a higher prevalence of needle-sharing. Phylogenetic analysis revealed that genotype 6a was predominant in the study population. There were shorter genetic distances among the 6a sequences compared to the other HCV subtypes-1a, 3a, and 3b. CONCLUSION/SIGNIFICANCE: The results suggested that HIV and HCV were introduced at around the same time to the IDU populations in Southern China, followed by their differential spread as determined by the biologic characteristics of the virus and the intensity of behavioural risk. This pattern is different from that in other South East Asian countries where HCV infections have probably predated HIV.

  14. Isolation and characterization of highly replicable hepatitis C virus genotype 1a strain HCV-RMT.

    Science.gov (United States)

    Arai, Masaaki; Tokunaga, Yuko; Takagi, Asako; Tobita, Yoshimi; Hirata, Yuichi; Ishida, Yuji; Tateno, Chise; Kohara, Michinori

    2013-01-01

    Multiple genotype 1a clones have been reported, including the very first hepatitis C virus (HCV) clone called H77. The replication ability of some of these clones has been confirmed in vitro and in vivo, although this ability is somehow compromised. We now report a newly isolated genotype 1a clone, designated HCV-RMT, which has the ability to replicate efficiently in patients, chimeric mice with humanized liver, and cultured cells. An authentic subgenomic replicon cell line was established from the HCV-RMT sequence with spontaneous introduction of three adaptive mutations, which were later confirmed to be responsible for efficient replication in HuH-7 cells as both subgenomic replicon RNA and viral genome RNA. Following transfection, the HCV-RMT RNA genome with three adaptive mutations was maintained for more than 2 months in HuH-7 cells. One clone selected from the transfected cells had a high copy number, and its supernatant could infect naïve HuH-7 cells. Direct injection of wild-type HCV-RMT RNA into the liver of chimeric mice with humanized liver resulted in vigorous replication, similar to inoculation with the parental patient's serum. A study of virus replication using HCV-RMT derivatives with various combinations of adaptive mutations revealed a clear inversely proportional relationship between in vitro and in vivo replication abilities. Thus, we suggest that HCV-RMT and its derivatives are important tools for HCV genotype 1a research and for determining the mechanism of HCV replication in vitro and in vivo.

  15. Isolation and characterization of highly replicable hepatitis C virus genotype 1a strain HCV-RMT.

    Directory of Open Access Journals (Sweden)

    Masaaki Arai

    Full Text Available Multiple genotype 1a clones have been reported, including the very first hepatitis C virus (HCV clone called H77. The replication ability of some of these clones has been confirmed in vitro and in vivo, although this ability is somehow compromised. We now report a newly isolated genotype 1a clone, designated HCV-RMT, which has the ability to replicate efficiently in patients, chimeric mice with humanized liver, and cultured cells. An authentic subgenomic replicon cell line was established from the HCV-RMT sequence with spontaneous introduction of three adaptive mutations, which were later confirmed to be responsible for efficient replication in HuH-7 cells as both subgenomic replicon RNA and viral genome RNA. Following transfection, the HCV-RMT RNA genome with three adaptive mutations was maintained for more than 2 months in HuH-7 cells. One clone selected from the transfected cells had a high copy number, and its supernatant could infect naïve HuH-7 cells. Direct injection of wild-type HCV-RMT RNA into the liver of chimeric mice with humanized liver resulted in vigorous replication, similar to inoculation with the parental patient's serum. A study of virus replication using HCV-RMT derivatives with various combinations of adaptive mutations revealed a clear inversely proportional relationship between in vitro and in vivo replication abilities. Thus, we suggest that HCV-RMT and its derivatives are important tools for HCV genotype 1a research and for determining the mechanism of HCV replication in vitro and in vivo.

  16. HCV and HCC molecular epidemiology

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    Flor H. Pujol

    2007-02-01

    Full Text Available

    iHepatitis C virus (HCV is a member of the family Flaviviridae, responsible for the majority of the non-A non-B post-transfusion hepatitis before 1990. Around 170 millions persons in the world are thought to be infected with this virus. A high number of HCV-infected people develop cirrhosis and from these, a significant proportion progresses to hepatocellular carcinoma (HCC. Six HCV genotypes and a large number of subtypes in each genotype have been described. Infections with HCV genotype 1 are associated with the lowest therapeutic success. HCV genotypes 1, 2, and 3 have a worldwide distribution. HCV subtypes 1a and 1b are the most common genotypes in the United States and are also are predominant in Europe, while in Japan, subtype 1b is predominant. Although HCV subtypes 2a and 2b are relatively common in America, Europe, and Japan, subtype 2c is found commonly in northern Italy. HCV genotype 3a is frequent in intravenous drug abusers in Europe and the United States. HCV genotype 4 appears to be prevalent in Africa and the Middle East, and genotypes 5 and 6 seem to be confined to South Africa and Asia, respectively. HCC accounts for approximately 6% of all human cancers. Around 500,000 to 1 million cases occur annually worldwide, with HCC being the fifth common malignancy in men and the ninth in women. HCC is frequently a consequence of infection by HBV and HCV. The first line of evidences comes from epidemiologic studies. While HBV is the most frequent cause of HCC in many countries of Asia and South America, both HBV and HCV are found at similar frequencies, and eventually HCV at a higher frequency than HBV, among HCC patients in Europe, North America, and Japan. The cumulative appearance rate of HCC might be higher for HCV

  17. The Distribution of Hepatitis C Virus Genotypes in Middle Eastern Countries: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Ghaderi-Zefrehi, Hossein; Gholami-Fesharaki, Mohammad; Sharafi, Heidar; Sadeghi, Farzin; Alavian, Seyed Moayed

    2016-09-01

    The hepatitis C virus (HCV) is classified into seven genotypes and more than 100 subtypes. The treatment regimen, duration and efficacy of HCV therapy may vary according to the HCV genotype. Therefore, the HCV genotype should be determined prior to antiviral therapy. The objective of the current study was to review systematically all studies reporting the distribution of HCV genotypes in the countries that make up the Middle East. Articles were identified by searching electronic databases, including Scopus, PubMed and Google scholar, with timeline limits (articles published between 1995 and 2016). We carried out a systematic search regarding the distribution of HCV genotypes in Middle Eastern countries. A total of 579 studies were identified by the electronic search. Of these, a total of 187 were identified as eligible papers including 60,319 patients who were meta-analyzed for pooled distribution of HCV genotypes. In Turkey, Israel, Cyprus, and Iran, genotype 1 was the most prevalent HCV genotype with rates of 82% (95% CI, 82%-83%), 68% (95% CI, 67%-69%), 68% (95% CI, 59%-77%), and 55% (95% CI, 54%-55%), respectively. In Egypt, Iraq, Saudi Arabia, and Syria, HCV genotype 4 was the most common genotype with rates of 86% (95% CI, 85%-88%), 60% (95% CI, 56%-64%), 56% (95% CI, 54%-55%), and 57% (95% CI, 54%-61%), respectively. On the basis of adjusted data, HCV genotype 4 was the most prevalent genotype in the Middle East region, with a rate of 74.7% (95% CI, 73.4%-76%), followed by genotype 1 at 15.1% (95% CI, 14.1%-16%). Our results showed that HCV genotype 4 is the most prevalent genotype in the Middle East region. However, HCV genotype 1 is the most prevalent among non-Arab countries in the region including Turkey, Iran, Cyprus, and Israel.

  18. Genotype 3 is the predominant hepatitis C genotype in a multi-ethnic Asian population in Malaysia.

    Science.gov (United States)

    Ho, Shiaw-Hooi; Ng, Kee-Peng; Kaur, Harvinder; Goh, Khean-Lee

    2015-06-01

    Genotypes of hepatitis C virus (HCV) are distributed differently across the world. There is a paucity of such data in a multi-ethnic Asian population like Malaysia. The objectives of this study were to determine the distribution of HCV genotypes between major ethnic groups and to ascertain their association with basic demographic variables like age and gender. This was a cross-sectional prospective study conducted from September 2007 to September 2013. Consecutive patients who were detected to have anti-HCV antibodies in the University of Malaya Medical Centre were included and tested for the presence of HCV RNA using Roche Cobas Amplicor Analyzer and HCV genotype using Roche single Linear Array HCV Genotyping strip. Five hundred and ninety-six subjects were found to have positive anti-HCV antibodies during this period of time. However, only 396 (66.4%) were HCV RNA positive and included in the final analysis. Our results showed that HCV genotype 3 was the predominant genotype with overall frequency of 61.9% followed by genotypes 1 (35.9%), 2 (1.8%) and 6 (0.5%). There was a slightly higher prevalence of HCV genotype 3 among the Malays when compared to the Chinese (P=0.043). No other statistical significant differences were observed in the distribution of HCV genotypes among the major ethnic groups. There was also no association between the predominant genotypes and basic demographic variables. In a multi-ethnic Asian society in Malaysia, genotype 3 is the predominant genotype among all the major ethnic groups with genotype 1 as the second commonest genotype. Both genotypes 2 and 6 are uncommon. Neither genotype 4 nor 5 was detected. There is no identification of HCV genotype according to ethnic origin, age and gender.

  19. Prevalence of HCV Infections Among Hemodialysis Patients in Al ...

    African Journals Online (AJOL)

    1527 patients (11%) who were HCV free at the start of the study. By the end of the study, a total of 42.2% were found to be anti-HCV reactive. Conclusion: The study demonstrated high prevalence of anti-HCV in HD units in Al Gharbiyah Governorate. Similar studies must be conducted in all Egyptian governorates' HD units ...

  20. Frequency of HCV infection and its genotypes among patients attending a liver clinic and voluntary blood donors in a rural area of Pakistan

    International Nuclear Information System (INIS)

    Abbas, S.Z.; Ali, M.; Muhammad, A.H.; Shaw, S.; Abbas, S.Q.

    2009-01-01

    Objectives: To determine the frequency of Hepatitis C virus (HCV) infection and its genotypic distribution in a rural area of Sindh, Pakistan. Methodology: Retrospective study of patients attending the Free Liver Clinic (FLC), and investigated for detectable HCV antibodies (n=1638), and those screened for HCV infection prior to voluntary blood donation (n=804) at a teaching hospital, located in rural Sindh. All patients had HCV antibodies tested by ELISA. A total of 1022 patients, who tested 'reactive' to HCV antibodies, and who could financially afford to have HCV RNA tested by PCR, had their results analysed. A total of 200 patients also had their HCV genotyped and analysed. Results: Patients at FLC had a higher chance of being reactive for HCV antibodies, compared to voluntary blood donors (20% VS 14% - p = 0.004). HCV RNA was detectable in 904/1022 (88%) patients. Among type able genotypes, 125/166 (75%) had a single genotype, and 7 patients (4%) were infected with genotype 1, either alone (n=4) or in combination with 3a. Conclusions: One out of every five people tested in our FLC, and 14% of 'healthy' voluntary blood donors were seropositive for HCV antibodies. Genotype 1 is very rare in our region. (author)

  1. Historical epidemiology of hepatitis C virus (HCV) in selected countries

    DEFF Research Database (Denmark)

    Bruggmann, P; Øvrehus, Anne Lindebo; Moreno, C

    2014-01-01

    Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained...

  2. Distribution of hepatitis C virus genotypes among injecting drug users in Lebanon

    Directory of Open Access Journals (Sweden)

    Shamra Sarah

    2010-05-01

    Full Text Available Abstract Background The aim of this study is to determine the prevalence of anti-HCV among injecting drug users (IDUs in Lebanon, to establish the current prevalence of HCV genotypes in this population and to determine whether demographic characteristics and behavioral variables differ between participants who were HCV-RNA positive and those who were HCV-RNA negative or between the different genotypes. Participants were recruited using respondent-driven sampling method. The blood samples were collected as dried blood spots and then eluted to be tested for HCV, HBV and HIV by ELISA. Anti-HCV positive samples were subjected to RNA extraction followed by qualitative detection and genotyping. Results Among 106 IDUs, 56 (52.8% were anti-HCV-positive. The two groups did not differ in terms of age, marital status, and nationality. As for the behavioral variable, there was a trend of increased risky behaviors among the HCV-RNA positive group as compared to the HCV-RNA negative group but none of the variables reached statistical significance. Half (50% of the 56 anti-HCV-positive were HCV-RNA positive. Genotype 3 was the predominant one (57.1% followed by genotype 1 (21% and genotype 4 (18%. Conclusions The predominance of genotype 3 seems to be the predominant genotype among IDUs in Lebanon, a situation similar to that among IDUs in Western Europe. This study provides a base-line against possible future radical epidemiological variant that might occur in IDUs.

  3. Prevalence of hepatitis C virus infection and HCV genotypes among hemophiliacs in the State of Bahia, Northeastern Brazil: analysis of serological and virological parameters Prevalência da infecção pelo vírus da hepatite C e genótipos entre hemofílicos no Estado da Bahia, nordeste do Brasil: análise de parâmetros sorológicos e virológicos

    Directory of Open Access Journals (Sweden)

    Luciano Kalabric Silva

    2005-12-01

    Full Text Available The objective of the present study was to analyze HCV serological and virological parameters from hemophiliacs in the State of Bahia. Anti-HCV was investigated by ELISA in a cohort of 268 hemophiliacs A/B who were followed-up in a reference unit for hemotherapy in the State of Bahia. HCV viremia and genotypes were also determined from a subset of 66 anti-HCV seropositive hemophiliacs. Seroprevalence among hemophiliacs was 42.2% (95% CI 36.5-48.1 and was significantly higher (p10 years, presence of factor VIII/IX inhibitory antibodies and other infection markers. None of the hemophiliacs less than 5 years of age were anti-HCV seropositive. Viremia was detectable in 77.3% (51/66. HCV genotype 1 (74% was the most prevalent followed by genotype 3 (22% and genotype 2 (4%. Our results indicate that HCV prevalence is still high among hemophiliacs, although HCV transmission was not observed in young hemophiliacs.O objetivo deste estudo foi analisar parâmetros sorológicos e virológicos em hemofílicos no Estado da Bahia. O anti-VHC foi investigado por ELISA em uma coorte de 268 hemofílicos A/B sob acompanhamento em uma unidade de referência do Estado da Bahia. A viremia do VHC e genótipos foram determinados em um subgrupo de 66 hemofílicos soropositivos para o anti-VHC. A soroprevalência do anti-VHC entre os hemofílicos foi de 42,2% (IC 95% 36,5-48,1 e foi associada significativamente (p10 anos, presença de anticorpos antifator VIII/IX e outros marcadores sorológicos de infecção. Nenhum dos hemofílicos com idade inferior a 5 anos foram anti-VHC positivos. A viremia foi detectada em 77,3% (51/66, sendo o genótipo 1 do VHC (74% o mais prevalente, seguido pelos genótipos 3 (22% e 2 (4%. Nossos resultados indicam que a prevalência do VHC é ainda alta entre os hemofílicos, muito embora a transmissão não tenha sido observada entre os menores de 5 anos.

  4. Naturally Occurring Resistance-Associated Variants to Hepatitis C Virus Direct-Acting Antiviral Agents in Treatment-Naive HCV Genotype 6a-Infected Patients

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    Zhanyi Li

    2017-01-01

    Full Text Available Background and Objective. The direct-acting antiviral agents (DAAs antiviral therapy has drastically improved the prognosis of hepatitis C virus (HCV patients. However, the viral drug resistance-associated variants (RAVs can limit the efficacy of DAAs. For the HCV-6a is not the predominant prevalent genotype; the data on the prevalence of naturally occurring RAVs in it is scarce. Our study aims to assess the prevalence of RAVs in treatment-naive HCV-6a patients. Methods. Nested PCR assays were performed on 95 HCV-6a patients to amplify HCV viral regions of NS3, NS5A, and NS5B. Results. In NS3/4A region, we detected Q80K in 95.5% isolates (84/88 and D168E in 2.3% isolates (2/88. In NS5A region, we detected Q30R in 93.2% isolates (82/88, L31M in 4.6% isolates (4/88, and H58P in 6.8% isolates (6/88. In NS5B region, we detected A15G in 2.3% isolates (2/88, S96T in 1.1% isolates (1/88, and S282T in 20.7% isolates (17/88 and we detected I482L in 100% isolates (4/4, V494A in 50% isolates (2/4, and V499A in 100% isolates (4/4. Conclusions. RAVs to DAAs preexist in treatment-naive HCV-6a patients. Further studies should address the issue of the impact of RAVs in response to DAA therapies for HCV-6a patients.

  5. Robust HCV Genotype 3a Infectious Cell Culture System Permits Identification of Escape Variants With Resistance to Sofosbuvir

    DEFF Research Database (Denmark)

    Ramirez Almeida, Santseharay; Mikkelsen, Lotte S.; Gottwein, Judith M.

    2016-01-01

    Background & Aims Direct-acting antivirals (DAAs) effectively eradicate chronic hepatitis C virus (HCV) infection, although HCV genotype 3a is less responsive to these drugs. We aimed to develop genotype 3a infectious cultures and study the effects of inhibitors of NS5A and NS5B and resistance to...

  6. Hepatitis C Virus: Viral Quasispecies and Genotypes.

    Science.gov (United States)

    Tsukiyama-Kohara, Kyoko; Kohara, Michinori

    2017-12-22

    Hepatitis C virus (HCV) mainly replicates in the cytoplasm, where it easily establishes persistent infection, resulting in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Due to its high rate of mutation, HCV forms viral quasispecies, categorized based on the highly variable regions in the envelope protein and nonstructural 5A protein. HCV possesses seven major genotypes, among which genotype 1 is the most prevalent globally. The distribution of HCV genotypes varies based on geography, and each genotype has a different sensitivity to interferon treatment. Recently-developed direct-acting antivirals (DAAs), which target viral proteases or polymerases, mediate drastically better antiviral effects than previous therapeutics. Although treatment with DAAs has led to the development of drug-resistant HCV mutants, the most recently approved DAAs show improved pan-genomic activity, with a higher barrier to viral resistance.

  7. Prevalence of hepatitis-C virus genotypes and potential transmission risks in Malakand Khyber Pakhtunkhwa, Pakistan.

    Science.gov (United States)

    Nazir, Nausheen; Jan, Muhammad Rasul; Ali, Amjad; Asif, Muhammad; Idrees, Muhammad; Nisar, Mohammad; Zahoor, Muhammad; Abd El-Salam, Naser M

    2017-08-22

    Hepatitis C virus (HCV) is a leading cause of chronic liver disease and frequently progresses towards liver cirrhosis and Hepatocellular Carcinoma (HCC). This study aimed to determine the prevalence of HCV genotypes and their association with possible transmission risks in the general population of Malakand Division. Sum of 570 serum samples were collected during March 2011 to January 2012 from suspected patients visited to different hospitals of Malakand. The suspected sera were tested using qualitative PCR and were then subjected to molecular genotype specific assay. Quantitative PCR was also performed for determination of pre-treatment viral load in confirmed positive patients. Out of 570 serum samples 316 sera were seen positive while 254 sera were found negative using qualitative PCR. The positive samples were then subjected to genotyping assay out of 316, type-specific PCR fragments were seen in 271 sera while 45 samples were found untypable genotypes. Genotype 3a was seen as a predominant genotype (63.3%) with a standard error of ±2.7%. Cramer's V statistic and Liklihood-Ratio statistical procedures are used to measure the strength and to test the association, respectively, between the dependent variable, genotype, and explanatory variables (e.g. gender, risk, age and area/districts). The dependent variable, genotype, is observed statistically significant association with variable risk factors. This implies that the genotype is highly dependent on how the patient was infected. In contrast, the other covariates, for example, gender, age, and district (area) no statistical significant association are observed. The association between gender-age indicates that the mean age of female was older by 10.5 ± 2.3 years with 95% confidence level using t-statistic. It was concluded from the present study that the predominant genotype was 3a in the infected population of Malakand. This study also highlights the high prevalence rate of untypable genotypes which an

  8. Hepatitis C Virus: Viral Quasispecies and Genotypes

    Directory of Open Access Journals (Sweden)

    Kyoko Tsukiyama-Kohara

    2017-12-01

    Full Text Available Hepatitis C virus (HCV mainly replicates in the cytoplasm, where it easily establishes persistent infection, resulting in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Due to its high rate of mutation, HCV forms viral quasispecies, categorized based on the highly variable regions in the envelope protein and nonstructural 5A protein. HCV possesses seven major genotypes, among which genotype 1 is the most prevalent globally. The distribution of HCV genotypes varies based on geography, and each genotype has a different sensitivity to interferon treatment. Recently-developed direct-acting antivirals (DAAs, which target viral proteases or polymerases, mediate drastically better antiviral effects than previous therapeutics. Although treatment with DAAs has led to the development of drug-resistant HCV mutants, the most recently approved DAAs show improved pan-genomic activity, with a higher barrier to viral resistance.

  9. Sofosbuvir and Simeprevir Combination Therapy for HCV Genotype 1 Infection: Results of a Single-Center VA Experience

    Science.gov (United States)

    Hernandez, Maria Del Pilar; Vance, Evan; Gilinski, Dani; Youtseff, Helen; Toro, Maribel; Antoine, Marie; Jeffers, Lennox J.; Peyton, Adam

    2016-01-01

    Treatment of chronic hepatitis C virus (HCV) infection remains a priority in the veterans affairs (VA) health care system nationwide, as there is a high burden of liver disease due to HCV infection among US veterans. The combination of sofosbuvir and simeprevir was the first all-oral antiviral regimen used in clinical practice to treat veterans with HCV infection. In this study, we report a single-center experience showing both the feasibility and effectiveness of this all-oral combination to treat HCV genotype 1 infection. One hundred patients with HCV genotype 1 infection were treated between December 2013 and June 2014. Eighty-six patients were treated with sofosbuvir and simeprevir, with or without ribavirin, for 12 weeks; 12 patients were treated with sofosbuvir, pegylated interferon, and ribavirin for 12 weeks; and 2 patients were treated with sofosbuvir and ribavirin for 24 weeks. Overall, treatment was well tolerated and feasible, with compliance rates over 95% in patients treated with all-oral therapy. The sustained virologic response (SVR) rate for sofosbuvir and simeprevir (88.4%) was superior to the rate for sofosbuvir, pegylated interferon, and ribavirin (50.0%). Subgroup analysis showed diminished SVR rates in cirrhotic patients vs noncirrhotic patients. There were no significant differences in SVR when comparing treatment with or without ribavirin or among genotype subtypes. In conclusion, this study demonstrated excellent completion rates for all-oral treatment of veterans with chronic HCV infection. Additionally, treatment was highly effective, nearing a 90% cure rate. Thus, we recommend that the VA health care system continue to incorporate new HCV medications into its formulary so as to expand HCV treatment for US veterans. PMID:27917084

  10. Hepatitis B virus infection in Chinese patients with hepatitis C virus infection: prevalence, clinical characteristics, viral interactions and host genotypes: a nationwide cross-sectional study.

    Science.gov (United States)

    Yan, Li-Bo; Rao, Hui-Ying; Ma, Yuan-Ji; Bai, Lang; Chen, En-Qiang; Du, Ling-Yao; Yang, Rui-Feng; Wei, Lai; Tang, Hong

    2016-10-12

    Little is known about hepatitis B virus (HBV) infection in patients with hepatitis C virus (HCV) infection in China. This study aimed to evaluate the prevalence, clinical characteristics, viral interactions and host genotypes of HBV/HCV dual infection compared with HCV monoinfection. A cross-sectional study. China. 997 patients with HCV from 28 university-affiliated hospitals in China were enrolled in this research. Patients were divided into two subgroups. The prevalence of HBV infection in patients with HCV was 4.11% (41/997). The age-specific prevalence of HBsAg was 0.70%, 3.97% and 5.85% in groups aged 18-30, 30-50 and >50 years old (p=0.057), respectively. Patients with HBV/HCV dual infection and patients with HCV monoinfection had similar HCV viral loads (5.80±0.89 vs 5.83±1.00 log10 IU/mL, p=0.904). The dominant HCV genotype was 1b in both groups (53.65% vs 56.90%, p=0.493). The protective C allele in IL-28B (rs12979860) was also the dominant allele type in both patient groups (85.36% vs 83.99%, p=0.814). Patients with HBV/HCV dual infection had a higher ratio of liver cirrhosis and hepatic decompensation than patients with HCV monoinfection (39.02% vs 17.69%, p=0.001; 31.70% vs 12.13%, p=0.001). The HBV burden was moderate in HCV-infected patients in China. Liver cirrhosis was more common in patients with HBV/HCV dual infection, suggesting the need for closer monitoring of dual-infected individuals. NCT01293279; Post-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. NS5A resistance-associated substitutions in patients with genotype 1 hepatitis C virus: Prevalence and effect on treatment outcome.

    Science.gov (United States)

    Zeuzem, Stefan; Mizokami, Masashi; Pianko, Stephen; Mangia, Alessandra; Han, Kwang-Hyub; Martin, Ross; Svarovskaia, Evguenia; Dvory-Sobol, Hadas; Doehle, Brian; Hedskog, Charlotte; Yun, Chohee; Brainard, Diana M; Knox, Steven; McHutchison, John G; Miller, Michael D; Mo, Hongmei; Chuang, Wan-Long; Jacobson, Ira; Dore, Gregory J; Sulkowski, Mark

    2017-05-01

    The efficacy of NS5A inhibitors for the treatment of patients chronically infected with hepatitis C virus (HCV) can be affected by the presence of NS5A resistance-associated substitutions (RASs). We analyzed data from 35 phase I, II, and III studies in 22 countries to determine the pretreatment prevalence of various NS5A RASs, and their effect on outcomes of treatment with ledipasvir-sofosbuvir in patients with genotype 1 HCV. NS5A gene deep sequencing analysis was performed on samples from 5397 patients in Gilead clinical trials. The effect of baseline RASs on sustained virologic response (SVR) rates was assessed in the 1765 patients treated with regimens containing ledipasvir-sofosbuvir. Using a 15% cut-off, pretreatment NS5A and ledipasvir-specific RASs were detected in 13% and 8% of genotype 1a patients, respectively, and in 18% and 16% of patients with genotype 1b. Among genotype 1a treatment-naïve patients, SVR rates were 91% (42/46) vs. 99% (539/546) for those with and without ledipasvir-specific RASs, respectively. Among treatment-experienced genotype 1a patients, SVR rates were 76% (22/29) vs. 97% (409/420) for those with and without ledipasvir-specific RASs, respectively. Among treatment-naïve genotype 1b patients, SVR rates were 99% for both those with and without ledipasvir-specific RASs (71/72 vs. 331/334), and among treatment-experienced genotype 1b patients, SVR rates were 89% (41/46) vs. 98% (267/272) for those with and without ledipasvir-specific RASs, respectively. Pretreatment ledipasvir-specific RASs that were present in 8-16% of patients have an impact on treatment outcome in some patient groups, particularly treatment-experienced patients with genotype 1a HCV. The efficacy of treatments using NS5A inhibitors for patients with chronic hepatitis C virus (HCV) infection can be affected by the presence of NS5A resistance-associated substitutions (RASs). We reviewed results from 35 clinical trials where patients with genotype 1 HCV infection

  12. HIV, HBV and HCV Coinfection Prevalence in Iran--A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Fahimeh Bagheri Amiri

    Full Text Available worldwide, hepatitis C and B virus infections (HCV and HCV, are the two most common coinfections with human immunodeficiency virus (HIV and has become a major threat to the survival of HIV-infected persons. The review aimed to estimate the prevalence of HIV, HBV, HCV, HIV/HCV and HIV/HBV and triple coinfections in different subpopulations in Iran.Following PRISMA guidelines, we conducted a systematic review and meta-analysis of reports on prevalence of HIV, HBV, HCV and HIV coinfections in different subpopulations in Iran. We systematically reviewed the literature to identify eligible studies from January 1996 to March 2012 in English or Persian/Farsi databases. We extracted the prevalence of HIV antibodies (diagnosed by Elisa confirmed with Western Blot test, HCV antibodies and HBsAg (with confirmatory laboratory test as the main primary outcome. We reported the prevalence of the three infections and coinfections as point and 95% confidence intervals.HIV prevalence varied from %0.00 (95% CI: 0.00-0.003 in the general population to %17.25 (95% CI: 2.94-31.57 in people who inject drugs (PWID. HBV prevalence ranged from % 0.00 (95% CI: 0.00-7.87 in health care workers to % 30.9 (95% CI: 27.88-33.92 in PWID. HCV prevalence ranged from %0.19 (95% CI: 0.00-0.66 in health care workers to %51.46 (95% CI: 34.30-68.62 in PWID. The coinfection of HIV/HBV and also HIV/HCV in the general population and in health care workers was zero, while the most common coinfections were HIV/HCV (10.95%, HIV/HBV (1.88% and triple infections (1.25% in PWID.We found that PWID are severely and disproportionately affected by HIV and the other two infections, HCV and HBV. Screenings of such coinfections need to be reinforced to prevent new infections and also reduce further transmission in their community and to others.

  13. Test of IL28B polymorphisms in chronic hepatitis C patients treated with PegIFN and ribavirin depends on HCV genotypes: results from a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Zhifang Jia

    Full Text Available Many studies have been published on the association between single nucleotide polymorphisms (SNP near the IL28B gene and response to the combined treatments of pegylated-interferon (PegIFN and ribavirin (RBV in chronic HCV-infected patients, but without identical conclusions. The aim of this study was to assess impact of the IL28B polymorphisms on the effect of HCV standard treatment using meta-analysis based method.Association studies between polymorphisms of rs12979860 or rs8099917 and response to PegIFN/RBV treatment in chronic HCV patients were retrieved from PubMed. Data of qualified studies on sustained virological response (SVR in different genotypes were extracted and analyzed using meta-analysis method in Stata 10 software.Thirty-four papers, containing 46 independent studies, were included in the analysis. In the HCV G1/4 patients without treatment history, individuals carrying rs12979860 CC genotype were more likely to achieve SVR (OR 3.97, 95%CI 3.29-4.80 compared to those carrying CT/TT genotypes. Similar results were observed in the HCV G1/4 patients with unsuccessful or unknown treatment history (OR 3.76, 95%CI 2.67-5.28 or in the patients co-infected with human immunodeficiency virus (OR 5.20, 95%CI 3.04-8.90. However, associations could not be observed in HCV G2/3 patients. For rs8099917, similar results were obtained for genotype TT compared to genotypes TG/GG, indicating that TT genotype was significantly associated with better treatment response in patients infected with genotype 1 or 4 HCV, but not genotype 2 or 3 HCV.Polymorphisms of rs12979860 and rs8099917 near IL28B only associate with the treatment response to PegIFN/RBV in patients infected with HCV genotype 1 or 4 but not with genotype 2 or 3, irrespective of the previous treatment history or HIV co-infected status. Therefore, identification of IL28B genotypes is necessary only in patients infected with relatively difficult-to-treat genotype 1 or 4 HCV.

  14. Tracing the epidemic history of hepatitis C virus genotypes in Saudi Arabia.

    Science.gov (United States)

    Khan, Anis; Al Balwi, Mohammed; AlAyyar, Latifah; AlAbdulkareem, Ibrahim; Albekairy, Abdulkareem; Aljumah, Abdulrahman

    2017-08-01

    HCV genotype 4 is highly prevalent in many Middle Eastern countries, yet little is known about the genotype's epidemic history at the subtype-level in this region. To address the dearth of data from Saudi Arabia (SA) we genotyped 230 HCV isolates in the core/E- and NS5B-region and analyzed using Bayesian phylogenetic approaches. HCV genotype 4 (HCV/4) was positive in 61.7% (142/230) of isolates belonging to 7 different subtypes with the predominance of 4d (73/142; 51.4%) followed by 4a (51/142; 35.9%). Phylogenetic analysis also revealed a distinct epidemiological cluster of HCV/4d for Saudi Arabia. HCV/1 appeared as the second most prevalent genotype positive in 31.3% (72/230) of isolates with the predominance of 1b (53/72; 73.6%) followed by 1a (16/72; 22.2%), and 1g (3/72; 4.1%). A small proportion of isolates belonged to HCV/3a (12/230; 5.2%), and HCV/2a (4/230; 1.7%). We estimate that the genotype 4 common ancestor existed around 1935 (1850-1985). Genotype 4 originated plausibly in Central Africa and multiple subtypes disseminated across African borders since ~1970, including subtype 4d which dominates current HCV infections in Saudi Arabia. The Bayesian skyline plot (BSP) analysis showed that genotype 4d entered the Saudi population in 1900. The effective number of HCV infections grew gradually until the second half of the 1950s and more rapidly until the early-80s through the use of imported blood units and blood products. Subsequently, the rate of HCV infection in the Saudi Arabian population was stabilized through effective screening of blood and infection control measures. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Efficient infectious cell culture systems of the hepatitis C virus (HCV) prototype strains HCV-1 and H77.

    Science.gov (United States)

    Li, Yi-Ping; Ramirez, Santseharay; Mikkelsen, Lotte; Bukh, Jens

    2015-01-01

    the cloning of the prototype strain HCV-1 genome. In 1997, two molecular clones of H77, the other HCV prototype strain, were shown to be infectious in chimpanzees, but not in vitro. HCV research was hampered by a lack of infectious cell culture systems, which became available only in 2005 with the discovery of JFH1 (genotype 2a), a genome that could establish infection in Huh7.5 cells. Recently, we developed in vitro infectious clones for genotype 1a (TN), 2a (J6), and 2b (J8, DH8, and DH10) strains by identifying key adaptive mutations. Globally, genotype 1 is the most prevalent. Studies using HCV-1 and H77 prototype sequences have generated important knowledge on HCV. Thus, the in vitro infectious clones developed here for these 1a strains will be of particular value in advancing HCV research. Moreover, our findings open new avenues for the culture adaptation of HCV isolates of different genotypes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. Natural prevalence of resistance-associated variants in hepatitis C virus NS5A in genotype 3a-infected people who inject drugs in Germany.

    Science.gov (United States)

    Walker, Andreas; Siemann, Holger; Groten, Svenja; Ross, R Stefan; Scherbaum, Norbert; Timm, Jörg

    2015-09-01

    People who inject drugs (PWID) are the most important risk group for incident Hepatitis C virus (HCV) infection. In PWID in Europe HCV genotype 3a is highly prevalent. Unfortunately, many of the recently developed directly acting antiviral drugs against HCV (DAAs) are suboptimal for treatment of this genotype. Detection of resistance-associated variants (RAV) in genotype 3a may help to optimize treatment decisions, however, robust protocols for amplification and sequencing of HCV NS5A as an important target for treatment of genotype 3a are currently lacking. The aim of this study was to establish a protocol for sequencing of HCV NS5A in genotype 3a and to determine the frequency of RAVs in treatment-naïve PWID living in Germany. The full NS5A region was amplified and sequenced from 110 HCV genotype 3a infected PWID using an in-house PCR protocol. With the established protocol the complete NS5A region was successfully amplified and sequenced from 110 out of 112 (98.2%) genotype 3a infected PWID. Phylogenetic analysis of sequences from PWID together with unrelated genotype 3a sequences from a public database showed a scattered distribution without geographic clustering. Viral polymorphisms A30K and Y93H known to confer resistance in a GT3a replication model were present in 8 subjects (7.2%). A protocol for amplification of nearly all GT3a samples was successfully established. Substitutions conferring resistance to NS5A inhibitors were detected in a few treatment-naive PWID. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Prevalence and Incidence of HCV Infection among Prisoners in Central Brazil.

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    Marco Antonio Moreira Puga

    Full Text Available The aim of this multicenter, cross sectional study was to assess the prevalence, incidence and associated risk factors among incarcerated populations from twelve Brazilian prisons. The total of 3,368 individuals from twelve prisons was randomly recruited between March 2013 and March 2014. Participants were interviewed, and provided blood samples which were tested for antibodies to Hepatitis C (HCV ab. One year after the first investigation, a cohort study was conducted with 1,656 inmates who participated the cross sectional study. Positive samples were tested for the presence of HCV RNA. Out of 3,368 inmates, 520 (15.4% were females, and 2,848 (84.6% were males. The overall prevalence of HCV was 2.4% (95% CI: 1.9 to 2.9, with 0.6% (95% CI: 0.4 to 0.8 in females, and 2.7% (95% CI: 2.1 to 3.3 in males (p<0.01. HCV RNA was detected in 51/80 (63.7% samples. Among men prisoners, multivariate analysis of associated factors showed independent associations between HCV exposure and increasing age, inject drug use, length of incarceration, smoking hashish, sharing needle and syringe and HIV positivity. During the cohort study, 7/1,656 new cases of HCV infection were detected, and the incidence rate was 0.4/100 person-year. Once high frequency rates of specific HCV risk behaviors and new HCV infections have been identified inside prisons, effective interventions strategies such as screening, clinical evaluation and treatment to reduce the spread of HCV infection are essential.

  18. Hepatitis C virus (HCV) RNA profiles among chronic HIV/HCV-coinfected individuals in ESPRIT; spontaneous HCV RNA clearance observed in nine individuals.

    Science.gov (United States)

    Grint, D; Tedaldi, E; Peters, L; Mocroft, A; Edlin, B; Gallien, S; Klinker, H; Boesecke, C; Kokordelis, P; Rockstroh, J K

    2017-07-01

    Studies have shown that hepatitis C virus (HCV) RNA levels remain stable over time in HIV/HCV-coinfected individuals taking combination antiretroviral therapy (cART), while spontaneous clearance of HCV RNA during the persistent infection phase has been documented only rarely among those with the CC interleukin (IL)-28B genotype. This study describes HCV RNA profiles and factors associated with changes over time in HCV RNA levels in the ESPRIT study. HIV/HCV-coinfected individuals positive for HCV RNA were included in the study. Follow-up was counted from the first HCV RNA positive test and censored at the initiation of interferon-based treatment. HCV RNA and IL-28B measurements were performed in the same reference laboratory. Random effects mixed models were used to analyse changes over time in HCV RNA. A total of 312 ESPRIT patients were included in the study (151 in the arm receiving subcutaneous recombinant IL-2 and 161 in the control arm). Most of the patients were white (89%) and male (76%), and they had a median of 5 HCV RNA measurements per person [interquartile range (IQR) 3-6; range 1-9]. Median follow-up was 5 years (IQR: 2-6 years). At baseline, 96% of patients were taking cART and 93% had undetectable HIV RNA. Mean HCV RNA levels decreased by 13% per year over the study period [95% confidence interval (CI) 8-18%; P < 0.0001]. Baseline HCV RNA levels and the change over time in HCV RNA did not differ by randomization arm (P = 0.16 and P = 0.56, respectively). Nine individuals spontaneously cleared HCV RNA during follow-up [IL-28B genotypes: CC, five patients (56%); CT, four patients (44%)]. HCV RNA levels decreased over time in this population with well-controlled HIV infection. Spontaneous clearance of HCV RNA was documented in five individuals with IL-28B genotype CC and four with the CT genotype. © 2016 British HIV Association.

  19. HBV And HCV Molecular Evolution

    Directory of Open Access Journals (Sweden)

    Flor H. Pujol

    2007-02-01

    hepatitis C virus (HCV. Six genotypes and a large number of subtypes in each genotype have been described for this member of the Flaviviridae family. Infections with HCV genotype 1 are associated with the lowest therapeutic success. HCV genotype 1b has also been more frequently associated with a more severe liver disease. However, this association seems to be due to the fact that individuals infected with this genotype have a longer mean duration of infection. HCV genotypes 1, 2, and 3 have a worldwide distribution and display an apidemic pattern of distribution. HCV subtypes 1a and 1b are the most common genotypes in the United States and are also are predominant in Europe, while in Japan, subtype 1b is predominant. Although HCV subtypes 2a and 2b are relatively common in America, Europe, and Japan, subtype 2c is found commonly in northern Italy. HCV genotype 3a is frequent in intravenous drug abusers in Europe and the United States. HCV genotype 4 appears to be prevalent in Africa and theMiddle East, and genotypes 5 and 6 seem to be confined to South Africa and Asia, respectively. These last genotypes display an endemic pattern of distribution. In addition, a change in the frequency of the prevailing genotypes has been described in several countries: in general, HCV genotype 1b is being displaced by genotypes 3a and/or 2. Coalescent studies have allowed to describe the epidemic pattern of dissemination of some HCV subtypes in specific countries, generally around 100 years ago. The origin of this virus is still an open question, but several studies traces it diversification only around 1,000 years ago.

    The replication of HCV is dependent on a RNA-polymerase RNA dependent which lacks proofreading activity, which confers to this virus a high rate of variability. This virus circulates as a quasispecies. This population dynamic inside a single strain confers to this virus the ability to

  20. Pegylated-interferon plus ribavirin treatment does not alter the prevalence of resistance-associated substitutions to direct-acting antivirals in HCV genotype 1a patients

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    Chen Z

    2017-08-01

    Full Text Available Zhi-wei Chen,* Xi-chen Pang,* Zhao Li, Hong Ren, Peng Hu Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China *These authors contributed equally to this work Background: Direct-acting antiviral (DAA resistance-associated substitutions (RASs can jeopardize the effectiveness of DAAs in patients with hepatitis C virus (HCV. The selection pressure by pegylated-interferon (Peg-IFN plus ribavirin (P/R treatment may enhance HCV genome variation. However, whether P/R treatment alters the rate of change of RASs is still unclear. Materials and methods: We retrieved the genomic sequences of HCV genotype (GT 1a patients from GenBank, which included patients naïve to P/R (pre-IFN group and those previously treated with P/R (post-IFN group. The sequences were aligned and analyzed by using MEGA 6.0 software. Clinically relevant RASs were summarized from the current medical literature. Results: In the cross-sectional study, the total prevalence of clinically relevant RASs was high, independent of the treatment group (pre-IFN: 219/403 [54.34%] vs post-IFN: 67/131 [51.15%]. The high prevalence was mainly detected in the NS3 region RAS at Q80 (40.69% vs 36.64%. The RASs in the NS5A region, such as M28, Q30, L31 and Y93, were uncommon (0%–5%. Similarly, all RASs showed no difference between the two groups. One exception was the RAS at I170 in the NS3 region, which was significantly higher in the post-IFN group than in the pre-IFN group. In the longitudinal study, similar results were observed. However, no difference in RAS at I170 was observed between the two groups. Finally, no clinically relevant RASs were detected in response to the DAA regimens approved for GT 1a patients treated with P/R. Conclusion: Our results suggest that previous P/R treatment failure was not

  1. Risk Factors and Genotypes of Hepatitis C Virus Infection in Libyan ...

    African Journals Online (AJOL)

    Background: The prevalence and incidence of HCV infection varies geographically due to exposure to different risk factors. Identification of HCV genotype is important to defining the epidemiology of the disease. The objective of this study was to describe genotype distribution and its relation to risk factors among HCV ...

  2. Small interfering RNA targeted to stem-loop II of the 5' untranslated region effectively inhibits expression of six HCV genotypes

    Directory of Open Access Journals (Sweden)

    Dash Srikanta

    2006-11-01

    Full Text Available Abstract Background The antiviral action of interferon alpha targets the 5' untranslated region (UTR used by hepatitis C virus (HCV to translate protein by an internal ribosome entry site (IRES mechanism. Although this sequence is highly conserved among different clinical strains, approximately half of chronically infected hepatitis C patients do not respond to interferon therapy. Therefore, development of small interfering RNA (siRNA targeted to the 5'UTR to inhibit IRES mediated translation may represent an alternative approach that could circumvent the problem of interferon resistance. Results Four different plasmid constructs were prepared for intracellular delivery of siRNAs targeting the stem loop II-III of HCV 5' UTR. The effect of siRNA production on IRES mediated translation was investigated using chimeric clones between the gene for green fluorescence protein (GFP and IRES sequences of six different HCV genotypes. The siRNA targeted to stem loop II effectively mediated degradation of HCV IRES mRNA and inhibited GFP expression in the case of six different HCV genotypes, where as siRNAs targeted to stem loop III did not. Furthermore, intracytoplasmic expression of siRNA into transfected Huh-7 cells efficiently degraded HCV genomic RNA and inhibited core protein expression from infectious full-length infectious clones HCV 1a and HCV 1b strains. Conclusion These in vitro studies suggest that siRNA targeted to stem-loop II is highly effective inhibiting IRES mediated translation of the major genotypes of HCV. Stem-loop II siRNA may be a good target for developing an intracellular immunization strategy based antiviral therapy to inhibit hepatitis C virus strains that are not inhibited by interferon.

  3. IFNL4 ss469415590 Variant Is Associated with Treatment Response in Japanese HCV Genotype 1 Infected Individuals Treated with IFN-Including Regimens

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    Tatsuo Miyamura

    2014-01-01

    Full Text Available Aim. Eradication of hepatitis C virus (HCV is still challenging even if interferon- (IFN- free regimens with direct-acting antiviral agents (DAAs for HCV-infected individuals are available in clinical practice. IFNL4 is a newly described protein, associated with human antiviral defenses. We investigated whether IFNL4 ss469415590 variant has an effect on the prediction of treatment response in HCV-infected patients treated with IFN-including regimens. Patients and Methods. In all, 185 patients infected with HCV genotype 1 treated with peg-IFN plus ribavirin, with or without telaprevir, were genotyped for IFNL4 ss469415590. We retrospectively investigated whether the role of IFNL4 ss469415590 variant and other factors could predict sustained virological response (SVR in Japanese patients infected with HCV genotype 1. Results. There were 65.7%, 31.5%, and 2.8% patients in the IFNL4 ss469415590 TT/TT, TT/-G, and -G/-G groups, respectively. SVR rates were 82.1% or 49.3% in patients treated with peg-IFN plus ribavirin with or without telaprevir, respectively. IFNL4 ss469415590 variant and HCV viral loads or IFNL4 ss469415590 variant and early virological response were better predictors of SVR in patients treated with peg-IFN plus ribavirin with or without telaprevir, respectively. Conclusion. In the era of DAAs, measurement of IFNL4 ss469415590 variant could help the prediction of SVR in Japanese HCV genotype 1 infected individuals treated with IFN-including regimens.

  4. A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans

    DEFF Research Database (Denmark)

    Law, John Lok Man; Chen, Chao; Wong, Jason

    2013-01-01

    of genotype 1a). Cross neutralization was tested in Huh-7.5 human hepatoma cell cultures using infectious recombinant HCV (HCVcc) expressing structural proteins of heterologous HCV strains from all known major genotypes, 1-7. Vaccination induced significant neutralizing antibodies against heterologous HCV...... genotype 1a virus which represents the most common genotype in North America. Of the 16 vaccinees tested, 3 were selected on the basis of strong 1a virus neutralization for testing of broad cross-neutralizing responses. At least 1 vaccinee was shown to elicit broad cross-neutralization against all HCV...

  5. HCV Core Antigen Testing for Diagnosis of HCV Infection: A systematic review and meta-analysis

    Science.gov (United States)

    Freiman, J. Morgan; Tran, Trang M.; Schumacher, Samuel G; White, Laura F.; Ongarello, Stefano; Cohn, Jennifer; Easterbrook, Philippa J.; Linas, Benjamin P.; Denkinger, Claudia M.

    2017-01-01

    Background Diagnosis of chronic Hepatitis C Virus (HCV) infection requires both a positive HCV antibody screen and confirmatory nucleic acid test (NAT). HCV core antigen (HCVcAg) is a potential alternative to NAT. Purpose This systematic review evaluated the accuracy of diagnosis of active HCV infection among adults and children for five HCVcAg tests compared to NAT. Data Sources EMBASE, PubMed, Web of Science, Scopus, and Cochrane from 1990 through March 31, 2016. Study Selection Cohort, cross-sectional, and randomized controlled trials were included without language restriction Data Extraction Two independent reviewers extracted data and assessed quality using an adapted Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Data Synthesis 44 studies evaluated 5 index tests. Studies for the ARCHITECT had the highest quality, while those for Ortho ELISA were the lowest. From bivariate analyses, the sensitivity and specificity with 95% CI were: ARCHITECT 93.4% (90.1, 96.4) and 98.8% (97.4, 99.5), Ortho ELISA 93.2% (81.6, 97.7) and 99.2% (87.9, 100), and Hunan Jynda 59.5% (46.0, 71.7) and 82.9% (58.6, 94.3). Insufficient data were available for a meta-analysis for Lumipulse and Lumispot. In three quantitative studies using ARCHITECT, HCVcAg correlated closely with HCV RNA above 3000 IU/mL. Limitations There was insufficient data on covariates such as HIV or HBV status for sub-group analyses. Few studies reported genotypes of isolates and there were scant data for genotypes 4, 5, and 6. Most studies were conducted in high resource settings within reference laboratories. Conclusions HCVcAg assays with signal amplification have high sensitivity, high specificity, and good correlation with HCV RNA above 3000 IU/mL. HCVcAg assays have the potential to replace NAT in high HCV prevalence settings. PMID:27322622

  6. Molecular genotyping of HCV infection in seropositive blood donor

    Science.gov (United States)

    Zarin, Siti Noraziah Abu; Ibrahim, Nazlina

    2013-11-01

    This study is to investigate the prevalence of hepatitis C virus infection in seropositive blood donor. RNA was extracted from 32 positive samples in National Blood Centre and Melaka Hospital. The core and NS5B sequences were obtained from 23 samples. Genotype 3a is most prevalent in this study followed by genotype 1a. Evidence of mixed-genotypes (3a and 1b) infections was found in 5 subjects.

  7. The Correlation between Different Risk Factors of Hepatitis C and Different Genotypes

    Science.gov (United States)

    Mokhtari, Mozhgan; Basirkazeruni, Hanieh; Rostami, Mojtaba

    2017-01-01

    Background: Hepatitis C infection is one of the health problems in the world. Several known risk factors are responsible in transmission of this infection. We are going to study the prevalence of these risk factors for different genotypes of hepatitis C and if possible, specify probable relations between each risk factor and transmission of each genotype. Materials and Methods: This is a cross-sectional study done on 270 people who had positive anti-hepatitis C virus (HCV) antibody and HCV RNA. Demographic specificity and possible risk factors were collected using a questionnaire, and statistical analysis was done by SPSS software (version 20). Chi-square test used to estimate the prevalence and relation between each qualitative risk factor and HCV genotype transmitted. Analysis of variance was used for studying the prevalence and relation between quantitative risk factors and HCV genotypes. Results: The sample size was 270 persons. Of these, 217 (80.4%) were men and 185 (68.5%) were infected with genotype Type III. Most people were in age range of 31–40 years old 92 (34%). Single people were 126 (46.7%) and 169 (62.6%) were high school and university graduated. Tattooing as a risk factor had a meaningful relation with hepatitis C genotype (P < 0.001). Conclusions: According to the findings, most people in central provinces of Iran with hepatitis C are carrying genotype III, with most prevalent risk factors such as intravenous drug use and unsafe sexual activity. Besides, tattooing had a significant association with hepatitis C genotype, so that in these groups of people, genotype I was more frequent isolated virus. PMID:28503500

  8. Epidemiology of hepatitis C virus and genotype distribution in immigrants crossing to Europe from North and sub-Saharan Africa.

    Science.gov (United States)

    Daw, Mohamed A; El-Bouzedi, Abdallah; Ahmed, Mohamed O; Dau, Aghnyia A; Agnan, Mohamed M

    The association between the prevalence of hepatitis C virus (HCV) and immigration is rarely studied, particularly for the immigrants crossing to the resettlement countries. Most of the published data are confined to those immigrants who were resident in European countries and rarely immigrated before they reach the final destination. Libya is a large country in North Africa with the longest coast of the Mediterranean Sea facing the European Union. It has been considered as the main transient station for African immigrants to Europe. The objectives of this study were to determine: (1) the prevalence of HCV in African immigrants gathered in Libya from different African countries on their way to Europe and (2) HCV genotype distribution in these immigrants and its correlation with different demographic factors. A total of 14 205 serum samples were collected in a 3-year period (2013-2015) from different immigrants from North and sub-Saharan Africa who resided in the African immigrant campus, Tripoli, Libya. The participants were interviewed, and relevant information was collected, including socio-demographic, ethnic, and geographic variables. Each serum sample was tested for anti-HCV antibody using ELISA. The genotypes were determined and assigned using a specific genotyping assay and correlated with demographic and potential risk factors of the recruited individuals. Of the immigrants studied, 1078 (7.6%) were positive for HCV. The prevalence of HCV infection ranged from 1.4% to 18.7%; it was higher among individuals arriving from Nile river (3.6-18.7%) of North Africa, followed by those who arrived from the West African region (2.1-14.1%), Horn of Africa (HOA, 6.8-9.9%), and Maghreb countries (1.4-2.7%). The relative risk factor attributable to gender variation was not significant (95% Cl: 0.8513-1.2381). Five genotypes were detected in 911 African immigrants. Genotypic analysis showed that the predominant HCV genotypes in this group were genotypes 4, 1, and 2 that

  9. Prevalence and characteristics of HIV/HBV and HIV/HCV coinfections in Tuscany

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    Monia Puglia

    2016-07-01

    Conclusions: We have observed less advanced disease in HIV and HCV-HIV patients compared with HBV–HIV coinfected patients. Moreover, our results show a higher prevalence of HIV/HCV among drug addicts and in the age-group 35–59, corresponding to those born in years considered most at risk for addiction. This study also confirms the finding of a less advanced HIV disease in HIV/HCV coinfected patients.

  10. IFN-Alpha receptor-1 upregulation in PBMC from HCV naïve patients carrying cc genotype. possible role of IFN-lambda.

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    Eleonora Lalle

    Full Text Available IL-28B gene polymorphisms predict better therapeutic response and spontaneous clearance of HCV. Moreover, higher expression of IFN-lambda has been reported in patients with the rs12979860 CC favourable genotype. The study aim was to establish possible relationships between IL-28B rs12979860 genotypes and expression of IFN-alpha receptor-1 (IFNAR-1 in naïve HCV patients, and to explore the possible role of IFN-lambda.IFNAR-1 mRNA levels were measured in PBMC from naïve patients with chronic hepatitis C with different IL-28 genotypes. The ability of IFN-lambda to up-regulate the expression of IFNAR-1 was established in PBMC from healthy donors carrying different IL-28B genotypes.Lower IFNAR-1 mRNA levels were observed in PBMC from HCV-infected naïve patients as compared to healthy donors. In healthy donors, IFNAR-1 mRNA levels were independent from IL-28B genotype, while in HCV patients, an increasing gradient was observed in TT vs CT vs CC carriers. In the latter group, a direct correlation between IFNAR-1 and endogenous IL-28B expression was observed. Moreover, IFN-lambda up-regulated IFNAR-1 expression in normal PBMC in a time-and dose-dependent manner, with a more effective response in CC vs TT carriers.Endogenous levels of IFN-lambda may be responsible for partial restoration of IFNAR-1 expression in HCV patients with favourable IL-28 genotype. This, in turn, may confer to CC carriers a response advantage to either endogenous or exogenous IFN-alpha, representing the biological basis for the observed association between CC genotype and favourable outcome of either natural infection (clearance vs chronicization or IFN therapy.

  11. Baseline HCV Antibody Prevalence and Risk Factors among Drug Users in China's National Methadone Maintenance Treatment Program.

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    Changhe Wang

    Full Text Available Hepatitis C virus (HCV is the most common viral infection among injecting drug users worldwide. We aimed to assess HCV antibody prevalence and associated risk factors among clients in the Chinese national methadone maintenance treatment (MMT program.Data from 296,209 clients who enrolled in the national MMT program between March 2004 and December 2012 were analyzed to assess HCV antibody prevalence, associated risk factors, and geographical distribution.Anti-HCV screening was positive for 54.6% of clients upon MMT entry between 2004 and 2012. HCV antibody prevalence at entry declined from 66.8% in 2005 to 45.9% in 2012. The most significant predictors of HCV seropositivity were injecting drug use (adjusted odds ratio [AOR]: 8.34, 95% confidence interval [CI]: 8.17-8.52, p<0.0001 and a history of drug use ≥9 years (AOR: 2.01, 95% CI: 1.96-2.06, p<0.0001. Being female, of Uyghur or Zhuang ethnicity, and unmarried were identified as demographic risk factors (all p-values<0.0001. Of the 28 provincial-level divisions included in the study, we found that 5 divisions had HCV antibody prevalence above 70% and 20 divisions above 50%. The HCV screening rate within 6 months after MMT entry greatly increased from 30.4% in 2004 to 93.1% in 2012.The current HCV antibody prevalence remains alarmingly high among MMT clients throughout most provincial-level divisions in China, particularly among injecting drug users and females. A comprehensive prevention strategy is needed to control the HCV epidemic among MMT clients in China.

  12. Hepatitis C in HIV-infected individuals: a systematic review and meta-analysis of estimated prevalence in Africa.

    Science.gov (United States)

    Azevedo, Tiago Castro Lopes; Zwahlen, Marcel; Rauch, Andri; Egger, Matthias; Wandeler, Gilles

    2016-01-01

    Although hepatitis C virus (HCV) screening is recommended for all HIV-infected patients initiating antiretroviral therapy, data on epidemiologic characteristics of HCV infection in resource-limited settings are scarce. We searched PubMed and EMBASE for studies assessing the prevalence of HCV infection among HIV-infected individuals in Africa and extracted data on laboratory methods used. Prevalence estimates from individual studies were combined for each country using random-effects meta-analysis. The importance of study design, population and setting as well as type of test (anti-HCV antibody tests and polymerase chain reactions) was examined with meta-regression. Three randomized controlled trials, 28 cohort studies and 121 cross-sectional analyses with 108,180 HIV-infected individuals from 35 countries were included. The majority of data came from outpatient populations (55%), followed by blood donors (15%) and pregnant women (14%). Based on estimates from 159 study populations, anti-HCV positivity prevalence ranged between 3.3% (95% confidence interval (CI) 1.8-4.7) in Southern Africa and 42.3% (95% CI 4.1-80.5) in North Africa. Study design, type of setting and age distribution did not influence this prevalence significantly. The prevalence of replicating HCV infection, estimated from data of 29 cohorts, was 2.0% (95% CI 1.5-2.6). Ten studies from nine countries reported the HCV genotype of 74 samples, 53% were genotype 1, 24% genotype 2, 14% genotype 4 and 9% genotypes 3, 5 or 6. The prevalence of anti-HCV antibodies is high in HIV-infected patients in Africa, but replicating HCV infection is rare and varies widely across countries.

  13. HCV Genotype 6a Escape From and Resistance to Velpatasvir, Pibrentasvir, and Sofosbuvir in Robust Infectious Cell Culture Models

    DEFF Research Database (Denmark)

    Pham, Long V; Ramirez, Santseharay; Gottwein, Judith M

    2018-01-01

    V was able to propagate and escape in the presence of pibrentasvir with emergence of NS5A-L28S, conferring a high level of resistance to this inhibitor. CONCLUSIONS: Strains of HCV genotype 6a isolated from patients can be adapted to propagate in cultured cells, permitting studies of the complete...... infectious cell culture models of HCV genotype 6a infection to study the effects of these inhibitors and the development of resistance. METHODS: The consensus sequences of prototype strains HK2 (MG717925) and HK6a (MG717928), originating from serum of patients with chronic HCV infection, were determined...... by Sanger sequencing of genomes amplified by reverse-transcription polymerase chain reaction. In vitro noninfectious full-length clones of these 6a strains were subsequently adapted in Huh7.5 cells, primarily by using substitutions identified in JFH1-based Core-NS5A and Core-NS5B genotype 6a recombinants...

  14. HCV Genotype 6a Escape from and Resistance to Velpatasvir, Pibrentasvir, and Sofosbuvir in Robust Infectious Cell Culture Models

    DEFF Research Database (Denmark)

    Pham, Long; Ramirez Almeida, Santseharay; Gottwein, Judith Margarete

    was able to propagate and escape in the presence of pibrentasvir with emergence of NS5A-L28S, conferring a high level of resistance to this inhibitor. CONCLUSIONS: Strains of HCV genotype 6a isolated from patients can be adapted to propagate in cultured cells, permitting studies of the complete life cycle...... infectious cell culture models of HCV genotype 6a infection to study the effects of these inhibitors and the development of resistance. METHODS: The consensus sequences of prototype strains HK2 (MG717925) and HK6a (MG717928), originating from serum of patients with chronic HCV infection, were determined...... by Sanger sequencing of genomes amplified by reverse transcription-PCR. In vitro non-infectious full-length clones of these 6a strains were subsequently adapted in Huh7.5 cells, primarily by using substitutions identified in JFH1-based core-NS5A and core-NS5B genotype 6a recombinants. We studied...

  15. Prevalence of HCV infection and associated factors among illicit drug users in Breves, State of Pará, northern Brazil

    OpenAIRE

    Pacheco,Suzy Danielly Barbosa; Silva-Oliveira,Gláucia Caroline; Maradei-Pereira,Luciana Maria Cunha; Crescente,José Ângelo Barletta; Lemos,José Alexandre Rodrigues de; Oliveira-Filho,Aldemir Branco de

    2014-01-01

    Introduction: Illicit drug users (DUs) are vulnerable to hepatitis C virus (HCV) infection. The shared use of illicit drugs is the main method of HCV transmission. Methods: A cross-sectional study was conducted in Breves, in northern Brazil. We surveyed 187 DUs to determine the prevalence of and factors associated with HCV infection. Results: The prevalence of anti-HCV antibodies was 36.9%, and the prevalence of hepatitis C virus-ribonucleic acid (HCV-RNA) was 31%. Hepatitis C virus infec...

  16. Polymorphisms associated with resistance to protease inhibitors in naïve patients infected with hepatitis C virus genotype 1 in Argentina: Low prevalence of Q80K.

    Science.gov (United States)

    Martínez, Alfredo P; Culasso, Andrés C A; Pérez, Paula S; Romano, Vanesa; Campos, Rodolfo H; Ridruejo, Ezequiel; García, Gabriel; Di Lello, Federico A

    2017-08-15

    Incorporation of direct acting antivirals (DAA) in the treatment of Hepatitis C Virus (HCV) significantly increases sustained virologic response rates. However, despite the greater potency offered by these antivirals, drug resistance plays a key role in patients with failure to DAA. Nevertheless, there is no information about the prevalence of resistance-associated substitutions (RASs) in Argentina. The aim of this study was to analyze HCV variants resistant to protease inhibitors (PI) in naïve patients infected with HCV genotype 1 from Argentina. In this retrospective cross-sectional study, 103 patients infected with HCV-1 were included. Eighteen positions related with RASs were analyzed by Sanger at baseline and phylogenetic analysis was performed to determine the diversification of this samples. The analyzed RASs were present in 38 out of 103 patients (36.9%) infected with HCV-1. Patients infected with subtype HCV-1b had higher prevalence of baseline RASs than patients infected with HCV-1a [51.6% vs. 12.8%, respectively (presistance in patients who will be treated with DAA in each particular country since the observed RASs have very different prevalence worldwide. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Hepatitis virus genotyping by Polymerase Chain Reaction and DNA Enzyme immunoassay among Saudi patients in the Western Province, Saudi Arabia

    International Nuclear Information System (INIS)

    Osoba, A.O.; Ibrahim, M.; Abdelaal, M.A.; Al-Mowallad, A.; Al-Shareef, B.; Hussein, B.A.

    2000-01-01

    The distribution of hepatitis C virus (HCV) genotypes in the Western Province of Saudi Arabia is unknown. The purpose of our study was to determine the prevalent HCV genotypes among HCV seropositive Saudi patients in the Western Province and to study the relationship between types/subtypes, clinical status and liver histology. Serum samples were collected from 140 consecutive patients attending the Hematology Clinic with varying grades of liver diseases, high almandine transferees (ALT) for > 6 months, positive HCV, qualitative PCR and who had liver biopsy. HCV genotyping was determined on patients who had tested positive by both HCV enzyme immunoassay (EIA) and the recombinant immunoblot assay (RIBA). Of the 140 patients, 97 (69.2%) had genotype 4, 18 (12.8%) had genotype 1a, and 16 (11.4%) had genotype 1b. Genotype 2b and 5 were found in two patients (1.4%) each, while 5 patients (3.6%) had mixed infections with genotype 4 and 5. Of the 97 patients infected with genotype 4, 84 (86.6%) had chronic active hepatitis (CAH), two (2.1%) had CAH with active cirrhosis, 9(9.3%) had cirrhosis and two (2.1%) had normal liver histology (NLH). The most prevalent HCV genotype in the Western Province of Saudi Arabia was genotype 4 (69.2%). Genotype 1b was encountered in 16 (11.4%) patients. For the first time, genotype 5 was identified in the Western Province of Saudi Arabia. Genotype 1b and 4 were associated with different histological grades of liver disease. (author)

  18. HCV treatment rates and sustained viral response among people who inject drugs in seven UK sites: real world results and modelling of treatment impact.

    Science.gov (United States)

    Martin, N K; Foster, G R; Vilar, J; Ryder, S; Cramp, M E; Gordon, F; Dillon, J F; Craine, N; Busse, H; Clements, A; Hutchinson, S J; Ustianowski, A; Ramsay, M; Goldberg, D J; Irving, W; Hope, V; De Angelis, D; Lyons, M; Vickerman, P; Hickman, M

    2015-04-01

    Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled-up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37-48% HCV chronic prevalence among PWID), East London (37-48%), Manchester (48-56%), Nottingham (37-44%), Plymouth (30-37%), Dundee (20-27%) and North Wales (27-33%). A model of HCV transmission among PWID projected the 10-year impact of (i) current treatment rates and SVR (ii) scale-up with interferon-free direct acting antivirals (IFN-free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention-to-treat SVR for PWID were 45% genotypes 1/4 [95%CI 33-57%] and 61% genotypes 2/3 [95%CI 47-76%]. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling-up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN-free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale-up, however, could lead to substantial reductions in HCV chronic prevalence. © 2014 The Authors Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.

  19. Genetic History of Hepatitis C Virus in Venezuela: High Diversity and Long Time of Evolution of HCV Genotype 2

    Science.gov (United States)

    Sulbarán, Maria Z.; Di Lello, Federico A.; Sulbarán, Yoneira; Cosson, Clarisa; Loureiro, Carmen L.; Rangel, Héctor R.; Cantaloube, Jean F.; Campos, Rodolfo H.; Moratorio, Gonzalo; Cristina, Juan; Pujol, Flor H.

    2010-01-01

    Background The subtype diversity of the hepatitis C virus (HCV) genotypes is unknown in Venezuela. Methodology/Principal Findings Partial sequencing of the NS5B region was performed in 310 isolates circulating in patients from 1995 to 2007. In the samples collected between 2005 and 2007, HCV genotype 1 (G1) was the most common genotype (63%), composed as expected of mainly G1a and G1b. G2 was the second most common genotype (33%), being G2a almost absent and G2j the most frequent subtype. Sequence analysis of the core region confirmed the subtype assignment performed within the NS5b region in 63 isolates. The complete genome sequence of G2j was obtained. G2j has been described in France, Canada and Burkina Fasso, but it was not found in Martinique, where several subtypes of G2 circulate in the general population. Bayesian coalescence analysis indicated a most recent common ancestor (MRCA) of G2j around 1785, before the introduction of G1b (1869) and G1a (1922). While HCV G1a and G1b experienced a growth reduction since 1990, coincident with the time when blood testing was implemented in Venezuela, HCV G2j did not seem to reach growth equilibrium during this period. Conclusions/Significance Assuming the introduction of G2j from Africa during the slave trade, the high frequency of G2j found in Venezuela could suggest: 1- the introduction of African ethnic groups different from the ones introduced to Martinique or 2- the occurrence of a founder effect. This study represents an in-depth analysis of the subtype diversity of HCV in Venezuela, which is still unexplored in the Americas and deserves further studies. PMID:21179440

  20. Genetic history of hepatitis C virus in Venezuela: high diversity and long time of evolution of HCV genotype 2.

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    Maria Z Sulbarán

    Full Text Available BACKGROUND: The subtype diversity of the hepatitis C virus (HCV genotypes is unknown in Venezuela. METHODOLOGY/PRINCIPAL FINDINGS: Partial sequencing of the NS5B region was performed in 310 isolates circulating in patients from 1995 to 2007. In the samples collected between 2005 and 2007, HCV genotype 1 (G1 was the most common genotype (63%, composed as expected of mainly G1a and G1b. G2 was the second most common genotype (33%, being G2a almost absent and G2j the most frequent subtype. Sequence analysis of the core region confirmed the subtype assignment performed within the NS5b region in 63 isolates. The complete genome sequence of G2j was obtained. G2j has been described in France, Canada and Burkina Fasso, but it was not found in Martinique, where several subtypes of G2 circulate in the general population. Bayesian coalescence analysis indicated a most recent common ancestor (MRCA of G2j around 1785, before the introduction of G1b (1869 and G1a (1922. While HCV G1a and G1b experienced a growth reduction since 1990, coincident with the time when blood testing was implemented in Venezuela, HCV G2j did not seem to reach growth equilibrium during this period. CONCLUSIONS/SIGNIFICANCE: Assuming the introduction of G2j from Africa during the slave trade, the high frequency of G2j found in Venezuela could suggest: 1- the introduction of African ethnic groups different from the ones introduced to Martinique or 2- the occurrence of a founder effect. This study represents an in-depth analysis of the subtype diversity of HCV in Venezuela, which is still unexplored in the Americas and deserves further studies.

  1. Prevalence of HCV infection and associated factors among illicit drug users in Breves, State of Pará, northern Brazil.

    Science.gov (United States)

    Pacheco, Suzy Danielly Barbosa; Silva-Oliveira, Gláucia Caroline; Maradei-Pereira, Luciana Maria Cunha; Crescente, José Ângelo Barletta; Lemos, José Alexandre Rodrigues de; Oliveira-Filho, Aldemir Branco de

    2014-01-01

    Illicit drug users (DUs) are vulnerable to hepatitis C virus (HCV) infection. The shared use of illicit drugs is the main method of HCV transmission. A cross-sectional study was conducted in Breves, in northern Brazil. We surveyed 187 DUs to determine the prevalence of and factors associated with HCV infection. The prevalence of anti-HCV antibodies was 36.9%, and the prevalence of hepatitis C virus-ribonucleic acid (HCV-RNA) was 31%. Hepatitis C virus infection was associated with tattoos, intravenous drug use, shared use of equipment for drug use, drug use for longer than 3 years, and daily drug use. Strategies for preventing and controlling HCV transmission should be implemented among DUs.

  2. HIV and HCV prevalence among entrants to methadone maintenance treatment clinics in China: a systematic review and meta-analysis

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    Zhuang Xun

    2012-06-01

    Full Text Available Abstract Background Methadone maintenance treatment (MMT was implemented in China since 2004. It was initiated in 8 pilot clinics and subsequently expanded to 738 clinics by the end of 2011. Numerous individual research studies have been conducted to estimate HIV and HCV prevalence among MMT clients but an overview of the epidemics in relations to MMT remains unclear. The aim of this study is to estimate the magnitude and changing trends of HIV, HCV and HIV-HCV co-infections among entry clients to MMT clinics in China during 2004-2010. Methods Chinese and English databases of literature were searched for studies reporting HIV, HCV and co-infection prevalence among MMT clients in China from 2004 to 2010. The prevalence estimates were summarized through a systematic review and meta-analysis of published literatures. Results Ninety eligible articles were selected in this review (2 in English and 88 in Chinese. Nationally, pooled prevalence of HIV-HCV and HIV-HCV co-infection among MMT clients was 6.0% (95%CI: 4.7%-7.7%, 60.1% (95%CI: 52.8%-67.0% and 4.6% (95%CI: 2.9%-7.2%, respectively. No significant temporal trend was found in pooled prevalence estimates. Study location is the major contributor of heterogeneities of both HIV and HCV prevalence among drug users in MMT. Conclusions There was no significant temporal trend in HIV and HCV prevalence among clients in MMT during 2004–2010. Prevalence of HCV is markedly higher than prevalence of HIV among MMT clients. It is recommended that health educational programs in China promote the earlier initiation and wider coverage of MMT among injecting drug users (IDUs, especially HIV-infected IDUs.

  3. An evidence of high prevalence of Hepatitis C virus in Faisalabad, Pakistan

    International Nuclear Information System (INIS)

    Ahmad, N.; Shafique, M.; Qureshi, Javed Anver; Asgher, M.

    2007-01-01

    To see the prevalence of Hepatitis C virus (HCV) and its genotypes in general population of the locality and to evaluate the importance of reverse transcriptase-polymerase chain reaction (RT-PCR) test over HCV antibody test in early diagnosis of HCV infection. The study took place at the National Institute for Biotechnology and Genetic Engineering (NIBGE) and we collected the samples from HCV screening camps organized by Allah Rakhi Trust Hospital Faisalabad and from blood donors visiting to Allied Hospital Faisalabad. Blood samples from 300 subjects (77% males and 23% females) with a mean average age of 32 +/- 20 years were randomly collected, and analyzed after separating the plasma by serological testing as well as molecular methods during the period from January 2004 to December 2004. Genotyping of HCV positive samples were performed by restriction fragment length polymorphism (RFLP) analysis of the PCR products. The results indicated that 48 (16%) cases were positive for anti-HCV antibody and 14 (4.7%) were on the borderline. Alanine aminotransferase (ALT) level indicated a wide range of activity from 5.0U/L to 128U/L. On the average, 79.4U/L activity was found. By nested PCR, 84 (28%) samples were positive for HCV-RNA. The results of genotyping have indicated that 8 (9.5%) samples were of genotype-1 while only 2 (2.4%) samples were of HCV genotype-2. Hepatitis C virus genotype-3 was found to be major prevalent genotype as it was present in 68 (81%) samples. Six (7.1%) samples could not be identified by this method thus remained un-typed. Hepatitis C virus-RNA detection by molecular method was found to be more sensitive for early diagnosis of HCV infection and relatively higher incidence of HCV infection with genotype-3 was found in general population of the area. (author)

  4. Hepatitis C virus prevalence and genetic diversity among pregnant women in Gabon, central Africa

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    Mahé Antoine

    2008-06-01

    Full Text Available Abstract Background Hepatitis C virus (HCV infection is a major global public health problem in both developed and developing countries. The prevalence and genetic diversity of HCV in pregnant women in Gabon, central Africa, is not known. We therefore evaluated the prevalence and the circulating genotypes of HCV in a large population cohort of pregnant women. Methods Blood samples (947 were collected from pregnant women in the five main cities of the country. The prevalence was evaluated by two ELISA tests, and the circulating genotypes were characterized by sequencing and phylogenetic analysis. Results Twenty pregnant women (2.1% were infected with HCV. The seroprevalence differed significantly by region (p = 0.004 and increased significantly with age (p = 0.05, being 1.3% at 14–20 years, 1.1% at 21–25 years, 1.9% at 26–30 years, 4.1% at 31–35 years and 6.0% at > 35 years. Sequencing in the 5'-UTR and NS5B regions showed that the circulating strains belonged to genotypes 4 (4e and 4c. Conclusion We found that the HCV seroprevalence in pregnant women in Gabon is almost as high as that in other African countries and increases with age. Furthermore, only genotype 4 (4e and 4c was found. More extensive studies aiming to evaluate the prevalence and heterogeneity of HCV genotypes circulating in the general population of the country are needed.

  5. Prevalence of HCV infection and associated factors among illicit drug users in Breves, State of Pará, northern Brazil

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    Suzy Danielly Barbosa Pacheco

    2014-06-01

    Full Text Available Introduction: Illicit drug users (DUs are vulnerable to hepatitis C virus (HCV infection. The shared use of illicit drugs is the main method of HCV transmission. Methods: A cross-sectional study was conducted in Breves, in northern Brazil. We surveyed 187 DUs to determine the prevalence of and factors associated with HCV infection. Results: The prevalence of anti-HCV antibodies was 36.9%, and the prevalence of hepatitis C virus-ribonucleic acid (HCV-RNA was 31%. Hepatitis C virus infection was associated with tattoos, intravenous drug use, shared use of equipment for drug use, drug use for longer than 3 years, and daily drug use. Conclusions: Strategies for preventing and controlling HCV transmission should be implemented among DUs.

  6. Serum Islet Cell Autoantibodies During Interferon α Treatment in Patients With HCV-Genotype 4 Chronic Hepatitis

    Directory of Open Access Journals (Sweden)

    Gamal Badra

    2006-01-01

    Full Text Available Chronic hepatitis C virus (HCV infection is a leading cause of end-stage liver disease worldwide and HCV genotype 4 (HCV4 is predominant in African and Middle Eastern countries. It is well established that interferon-α (IFNa treatment for HCV may trigger serum autoantibodies against pancreatic islet cells (ICA in a subgroup of patients. Available data on the incidence of ICA during IFNa therapy for chronic HCV4 infection are not conclusive. We investigated the appearance of ICA in 40 naïve Egyptian patients (38 males, 32 ± 6 years with histologically defined chronic HCV4 infection undergoing IFNa treatment at a dose of 9-million U/week for 24 weeks. Serum samples were collected at baseline and following IFNa therapy and ICA were detected using indirect immunofluorescence. Baseline evaluation indicated that 2/40 (5% patients had detectable serum ICA. After the completion of the treatment scheme, 12/38 (32% previously ICA negative patients became ICA positive; however, no patient developed impaired glucose tolerance (IGT or diabetes during follow-up. In conclusion, we submit that IFNa treatment for chronic hepatitis C (CHC may induce serum ICA in one-third of Egyptian patients with HCV4. These autoantibodies, however, do not lead to alterations in glucose metabolism.

  7. Evaluation of the Abbott realtime HCV genotype II RUO (GT II) assay with reference to 5'UTR, core and NS5B sequencing.

    Science.gov (United States)

    Mallory, Melanie A; Lucic, Danijela X; Sears, Mitchell T; Cloherty, Gavin A; Hillyard, David R

    2014-05-01

    HCV genotyping is a critical tool for guiding initiation of therapy and selecting the most appropriate treatment regimen. To evaluate the concordance between the Abbott GT II assay and genotyping by sequencing subregions of the HCV 5'UTR, core and NS5B. The Abbott assay was used to genotype 127 routine patient specimens and 35 patient specimens with unusual subtypes and mixed infection. Abbott results were compared to genotyping by 5'UTR, core and NS5B sequencing. Sequences were genotyped using the NCBI non-redundant database and the online genotyping tool COMET. Among routine specimens, core/NS5B sequencing identified 93 genotype 1s, 13 genotype 2s, 15 genotype 3s, three genotype 4s, two genotype 6s and one recombinant specimen. Genotype calls by 5'UTR, core, NS5B sequencing and the Abbott assay were 97.6% concordant. Core/NS5B sequencing identified two discrepant samples as genotype 6 (subtypes 6l and 6u) while Abbott and 5'UTR sequencing identified these samples as genotype 1 with no subtype. The Abbott assay subtyped 91.4% of genotype 1 specimens. Among the 35 rare specimens, the Abbott assay inaccurately genotyped 3k, 6e, 6o, 6q and one genotype 4 variant; gave indeterminate results for 3g, 3h, 4r, 6m, 6n, and 6q specimens; and agreed with core/NS5B sequencing for mixed specimens. The Abbott assay is an automated HCV genotyping method with improved accuracy over 5'UTR sequencing. Samples identified by the Abbott assay as genotype 1 with no subtype may be rare subtypes of other genotypes and thus require confirmation by another method. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Hepatitis C virus infection in Guinea-Bissau: a sexually transmitted genotype 2 with parenteral amplification?

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    Mireille Plamondon

    Full Text Available BACKGROUND: Sub-Saharan Africa is the continent with the highest prevalence of Hepatitis C virus (HCV infection. Genotype 2 HCV is thought to have originated from West Africa several hundred years ago. Mechanisms of transmission remain poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: To delineate mechanisms for HCV transmission in West Africa, we conducted a cross-sectional survey of individuals aged >or=50 years in Bissau, Guinea-Bissau. Dried blood spots were obtained for HCV serology and PCR amplification. Prevalence of HCV was 4.4% (47/1066 among women and 5.0% (27/544 among men. In multivariate analysis, the independent risk factors for HCV infection were age (baseline: 50-59 y; 60-69 y, adjusted odds ratio [AOR]: 1.67, 95% CI: 0.91-3.06; >or=70 y, AOR: 3.47, 95% CI: 1.89-6.39, belonging to the Papel, Mancanha, Balanta or Mandjako ethnic groups (AOR: 2.45, 95% CI:1.32-4.53, originating from the Biombo, Cacheu or Oio regions north of Bissau (AOR: 4.16, 95% CI: 1.18-14.73 and having bought or sold sexual services (AOR: 3.60, 95% CI: 1.88-6.89. Of 57 isolates that could be genotyped, 56 were genotype 2. CONCLUSIONS: Our results suggest that transmission of HCV genotype 2 in West Africa occurs through sexual intercourse. In specific locations and subpopulations, medical interventions may have amplified transmission parenterally.

  9. Prevalence of polymorphisms with significant resistance to NS5A inhibitors in treatment-naive patients with hepatitis C virus genotypes 1a and 3a in Sweden.

    Science.gov (United States)

    Lindström, Ida; Kjellin, Midori; Palanisamy, Navaneethan; Bondeson, Kåre; Wesslén, Lars; Lannergard, Anders; Lennerstrand, Johan

    2015-08-01

    The future treatment of hepatitis C virus (HCV) infection will be combinations of direct-acting antivirals (DAAs) that not only target multiple viral targets, but are also effective against different HCV genotypes. Of the many drug targets in HCV, one promising target is the non-structural 5A protein (NS5A), against which inhibitors, namely daclatasvir, ledipasvir and ombitasvir, have shown potent efficacy. However, since HCV is known to have very high sequence diversity, development of resistance is a problem against but not limited to NS5A inhibitors (i.e. resistance also found against NS3-protease and NS5B non-nucleoside inhibitors), when used in suboptimal combinations. Furthermore, it has been shown that natural resistance against DAAs is present in treatment-naïve patients and such baseline resistance will potentially complicate future treatment strategies. A pan-genotypic population-sequencing method with degenerated primers targeting the NS5A region was developed. We have investigated the prevalence of baseline resistant variants in 127 treatment-naïve patients of HCV genotypes 1a, 1b, 2b and 3a. The method could successfully sequence more than 95% of genotype 1a, 1b and 3a samples. Interpretation of fold resistance data against the NS5A inhibitors was done with the help of earlier published phenotypic data. Baseline resistance variants associated with high resistance (1000-50,000-fold) was found in three patients: Q30H or Y93N in genotype 1a patients and further Y93H in a genotype 3a patient. Using this method, baseline resistance can be examined and the data could have a potential role in selecting the optimal and cost-efficient treatment for the patient.

  10. Telaprevir for previously treated chronic HCV infection

    NARCIS (Netherlands)

    McHutchison, John G.; Manns, Michael P.; Muir, Andrew J.; Terrault, Norah A.; Jacobson, Ira M.; Afdhal, Nezam H.; Heathcote, E. Jenny; Zeuzem, Stefan; Reesink, Hendrik W.; Garg, Jyotsna; Bsharat, Mohammad; George, Shelley; Kauffman, Robert S.; Adda, Nathalie; Di Bisceglie, Adrian M.; Heathcote, E. J.; Kaita, K.; Ma, M.; Myers, R.; Sherman, M.; Yoshida, E.; Berg, T.; Manns, M. P.; Zeuzem, S.; de Knegt, R.; van Hoek, B.; Afdhal, N. H.; Arora, S.; Bernstein, D.; Cochran, J.; Di Bisceglie, A. M.; Dickson, R.; Dieterich, D. T.; Etzkorn, K.; Everson, G. T.; Faruqui, S.; Ghalib, R.; Gitlin, N.; Godofsky, E.; Gordon, S.; Hassanein, T.; Jacobson, I. M.; Kilby, A.; Kugelmas, M.; Kwo, P. Y.; Lawitz, E. S.; Lindsay, K.; Maillard, M.; Nelson, D. R.; Nyberg, L.

    2010-01-01

    Patients with genotype 1 hepatitis C virus (HCV) who do not have a sustained response to therapy with peginterferon alfa and ribavirin have a low likelihood of success with retreatment. We randomly assigned patients with HCV genotype 1 who had not had a sustained virologic response after

  11. Genetic variations of the NPC1L1 gene associated with hepatitis C virus (HCV) infection and biochemical characteristics of HCV patients in China.

    Science.gov (United States)

    Zhang, A-Mei; Zhang, Cheng-Lin; Song, Yuzhu; Zhao, Ping; Feng, Yue; Wang, Binghui; Li, Zheng; Liu, Li; Xia, Xueshan

    2016-12-01

    About 2% of the world population is infected with hepatitis C virus (HCV), a leading cause of hepatic cirrhosis and hepatocellular carcinoma. The Niemann-Pick C1-like 1 cholesterol absorption receptor (NPC1L1) was recently identified to be an important factor for HCV entry into host cells. Whether genetic variations of the NPC1L1 gene are associated with HCV infection is unknown. In this study, five single nucleotide polymorphisms (SNPs) of the NPC1L1 gene were analyzed in 261 HCV-infected individuals and 265 general controls from Yunnan Province, China. No significant differences were identified in genotypes or alleles of the SNPs between the two groups. After constructing haplotypes based on the five SNPs, a significant difference between HCV-infected individuals and general controls was shown for two haplotypes. Haplotype GCCTT appeared to be a protective factor and haplotype GCCCT was a risk factor for HCV-infected individuals. Genotypes of four SNPs correlated with biochemical characteristics of HCV-infected persons. Genotypes of SNPs rs799444 and rs2070607 were correlated with total bilirubin. Genotype TT of rs917098 was a risk factor for the gamma-glutamyltransferase level. Furthermore, HCV-infected individuals carrying genotype GG of rs41279633 showed statistically higher gamma-glutamyltransferase levels than HCV-infected persons with GT and TT. The results of this study identified the association between genetic susceptibility of the NPC1L1 gene and HCV infection, as well as biochemical characteristics of HCV-infected persons in Yunnan, China. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. Emergence of hepatitis C virus genotype 4: phylogenetic analysis reveals three distinct epidemiological profiles

    NARCIS (Netherlands)

    de Bruijne, Joep; Schinkel, Janke; Prins, Maria; Koekkoek, Sylvie M.; Aronson, Sem J.; van Ballegooijen, Marijn W.; Reesink, Hendrik W.; Molenkamp, Richard; van de Laar, Thijs J. W.

    2009-01-01

    Hepatitis C virus (HCV) genotype 4 (HCV-4) infection is considered to be difficult to treat and has become increasingly prevalent in European countries, including The Netherlands. Using a molecular epidemiological approach, the present study investigates the genetic diversity and evolutionary origin

  13. Risk factors and genotypes of hepatitis C virus infection in libyan patients.

    Science.gov (United States)

    Alashek, Wa; Altagdi, M

    2008-12-01

    The prevalence and incidence of HCV infection varies geographically due to exposure to different risk factors. Identification of HCV genotype is important to defining the epidemiology of the disease. The objective of this study was to describe genotype distribution and its relation to risk factors among HCV infected patients attending virology clinic of the Department of Infectious Diseases at the Tripoli Medical Centre. The medical records of 891 Libyan chronic HCV infected patients registered and followed up from January 2003 to January 2007 were reviewed. Data gathered includes patient's age, gender, risk factors and family history of HCV infection. Statistical analysis was performed using t, x2 and contingency coefficient tests. The mean age was 40.22±13.09 years. Two thirds of patients were males. Normal alanine aminotransferase (ALT) at diagnosis was found in 62% of the patients. HCV RNA<2 million copies at diagnosis was found among 54% of patients. HCV genotype 1 (G1) was the most frequent (30.9%), followed by G4 (29.2%). Genotype 2 affected 19.3% and G3 13.6%. No classification of HCV genotype was available for 2% of the patients. Many subtypes of HCV were detected with different frequencies (G1a and b, G2a, b, c and a/c, G3a and G4a and c/d). All genotypes of HCV were more common among males (P<0.001). Genotype 3 was the most frequent among male patients (88.6%). Regarding the risk factors, 33% of patients had a history of hospitalization and/or surgical procedures, and 22.7% had a history of blood transfusion. A past history of intravenous drug abuse (IVDA) was reported by 15% of the patients, and 15.9% reported a history of dental procedures. The relationship between the genotype of HCV and risk factors was statistically significant (P<0.001). No history of risky exposure was found among 10.8% of patients. Genotypes 1 and 4 were more predominant among HCV infected patients. Males were affected more than females and they presented themselves to the

  14. 5′ UTR and NS5B-based genotyping of hepatitis C virus in patients from Damietta governorate, Egypt

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    Radwa R. El-Tahan

    2018-03-01

    Full Text Available Chronic hepatitis C virus (HCV infection is a main health problem in Egypt causing high rates of mortalities. Egypt has the highest HCV prevalence in the world, with specific HCV subtypes epidemic and circulating extensively in the country. Different antiviral therapy protocols have been implemented for treating Egyptian HCV patients. Due to the limited data about HCV in Egypt, this study aimed to genotype HCV strains circulating in the Nile Delta Damietta governorate and to investigate the variation in the nonstructural 5B (NS5B region targeted by the newly approved antiviral drugs. Thirty HCV samples from treatment-naïve patients were genotyped by restriction fragment length polymorphism. Some samples were genotyped by direct sequencing of their 5′ untranslated region (UTR and NS5B regions. Phylogenetic analysis was also performed on the sequences of their NS5B regions. Fourteen new sequences have been deposited in the GenBank database. Results showed that subtype 4a was prevalent in addition to subtype 1g. None of the previously reported NS5B substitutions were detected in the sequenced isolates from treatment-naïve patients, which may be a good predictor for efficient treatment of HCV Egyptian patients with Sofosbuvir. Further studies on Sofosbuvir treated-HCV Egyptian patients are required to investigate whether any NS5B substitutions can confer resistance to treatment.

  15. Characterization of vaniprevir, a hepatitis C virus NS3/4A protease inhibitor, in patients with HCV genotype 1 infection: safety, antiviral activity, resistance, and pharmacokinetics.

    Science.gov (United States)

    Lawitz, Eric; Sulkowski, Mark; Jacobson, Ira; Kraft, Walter K; Maliakkal, Benedict; Al-Ibrahim, Mohamed; Gordon, Stuart C; Kwo, Paul; Rockstroh, Juergen Kurt; Panorchan, Paul; Miller, Michelle; Caro, Luzelena; Barnard, Richard; Hwang, Peggy May; Gress, Jacqueline; Quirk, Erin; Mobashery, Niloufar

    2013-09-01

    Vaniprevir is a competitive inhibitor of the hepatitis C virus (HCV) NS3/4A protease that has potent anti-HCV activity in preclinical models. This placebo-controlled dose-ranging study assessed the safety, tolerability, and antiviral efficacy of vaniprevir monotherapy in patients with genotype 1 chronic HCV infection. Treatment-naive and treatment-experienced non-cirrhotic adult patients with baseline HCV RNA >10(6)IU/ml were randomized to receive placebo or vaniprevir at doses of 125 mg qd, 600 mg qd, 25mg bid, 75 mg bid, 250 mg bid, 500 mg bid, and 700 mg bid for 8 days. Forty patients (82.5% male, 75% genotype 1a) received at least one dose of placebo or vaniprevir. After 1 week of vaniprevir, the decrease in HCV RNA from baseline ranged from 1.8 to 4.6 log₁₀IU/ml across all treatment groups, and there was a greater than dose-proportional increase in vaniprevir exposure at doses above 75 mg bid. The most commonly reported drug-related adverse events (AEs) were diarrhea (n=5) and nausea (n=5). No pattern of laboratory or ECG abnormalities was observed, all AEs resolved during the study, and there were no discontinuations due to AEs. No serious AEs were reported. Resistance-associated amino acid variants were identified at positions R155 and D168 in patients infected with genotype 1a virus. Vaniprevir monotherapy demonstrated potent antiviral activity in patients with chronic genotype 1 HCV infection, and was generally well tolerated with no serious AEs or discontinuations due to AEs. Further development of vaniprevir, including studies in combination with other anti-HCV agents, is ongoing. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Design, synthesis and identification of silicon-containing HCV NS5A inhibitors with pan-genotype activity.

    Science.gov (United States)

    Liu, Baomin; Gai, Kuo; Qin, Hui; Liu, Xushi; Cao, Yuan; Lu, Qin; Lu, Dandan; Chen, Deyang; Shen, Hengqiao; Song, Wei; Zhang, Yang; Wang, Xiaojin; Xu, Hongjiang; Zhang, Yinsheng

    2018-03-25

    Modification of a HCV NS5A inhibitor, ombitasvir, led to the identification of 10d with improved pan-genotype NS5A inhibition and better pharmacokinetic properties. The key structural changes to ombitasvir include bioisosteric replacement of carbon with silicon atom. Compared with ombitasvir, the activity of anti-HCV genotypes (GT 1 to 6) of 10d is increased to some extent, especially the inhibitory activity against genotype 3a and 6a is increased by more than seven times, and the dog's in vivo pharmacokinetics properties were also superior to ombitasvir. Further drug evaluation showed that 10d was similar to ombitasvir on plasma protein binding and liver distribution profiles, with no cytotoxicity and no inhibitory effect on both CYP 450 and hERG ligand binding. However, permeability assay results indicated that 10d was not the substrate of P-gp or BCRP transporter, which is different from that of ombitasvir. The results of a 14-day repeat-dose toxicity study identified no toxicity with 10d. Our findings in preclinical tests suggest that the silicon-containing compound 10d could be worthy of continued study as a potential drug candidate. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  17. Hepatitis C prevalence among HIV-infected patients in Guinea-Bissau

    DEFF Research Database (Denmark)

    Hønge, Bo Langhoff; Jespersen, Sanne; Medina, Candida

    2014-01-01

    Objectives: To estimate the prevalence and determine the clinical presentation of risk factors of hepatitis C virus (HCV) among HIV-infected patients in Bissau, Guinea-Bissau. Methods: In this cross-sectional study, we included individuals who had a routine blood analysis performed during...... the period April 28 to September 30, 2011. Patient samples were tested for HCV antibodies (anti-HCV) with a chemiluminescence test (Architect, Abbott, USA) and INNO-LIA HCV Score (Innogenetics, Belgium). HCV viral load and genotype were analyzed using an in-house real-time PCR method. Results: In total, 576...... patients were included (417 HIV-1, 104 HIV-2, and 55 HIV-1/2). Ten (1.7%) patients were anti-HCV-positive and eight (1.4%) patients had detectable HCV RNA; all were genotype 2. In a multivariable logistic regression analysis, age >50 years was associated with anti-HCV reactivity (p

  18. Analytical characteristics and comparative evaluation of Aptima HCV quant Dx assay with the Abbott RealTime HCV assay and Roche COBAS AmpliPrep/COBAS TaqMan HCV quantitative test v2.0.

    Science.gov (United States)

    Worlock, A; Blair, D; Hunsicker, M; Le-Nguyen, T; Motta, C; Nguyen, C; Papachristou, E; Pham, J; Williams, A; Vi, M; Vinluan, B; Hatzakis, A

    2017-04-04

    The Aptima HCV Quant Dx assay (Aptima assay) is a fully automated quantitative assay on the Panther® system. This assay is intended for confirmation of diagnosis and monitoring of HCV RNA in plasma and serum specimens. The purpose of the testing described in this paper was to evaluate the performance of the Aptima assay. The analytical sensitivity, analytical specificity, precision, and linearity of the Aptima assay were assessed. The performance of the Aptima assay was compared to two commercially available HCV assays; the Abbott RealTime HCV assay (Abbott assay, Abbott Labs Illinois, USA) and the Roche COBAS Ampliprep/COBAS Taqman HCV Quantitative Test v2.0 (Roche Assay, Roche Molecular Systems, Pleasanton CA, USA). The 95% Lower Limit of Detection (LoD) of the assay was determined from dilutions of the 2nd HCV WHO International Standard (NIBSC 96/798 genotype 1) and HCV positive clinical specimens in HCV negative human plasma and serum. Probit analysis was performed to generate the 95% predicted detection limits. The Lower Limit of Quantitation (LLoQ) was established for each genotype by diluting clinical specimens and the 2nd HCV WHO International Standard (NIBSC 96/798 genotype 1) in HCV negative human plasma and serum. Specificity was determined using 200 fresh and 536 frozen HCV RNA negative clinical specimens including 370 plasma specimens and 366 serum specimens. Linearity for genotypes 1 to 6 was established by diluting armored RNA or HCV positive clinical specimens in HCV negative serum or plasma from 8.08 log IU/mL to below 1 log IU/mL. Precision was tested using a 10 member panel made by diluting HCV positive clinical specimens or spiking armored RNA into HCV negative plasma and serum. A method comparison was conducted against the Abbott assay using 1058 clinical specimens and against the Roche assay using 608 clinical specimens from HCV infected patients. In addition, agreement between the Roche assay and the Aptima assay using specimens with low

  19. Risk Factors and Genotypes of Hepatitis C Virus Infection in Libyan Patients

    Directory of Open Access Journals (Sweden)

    Alashek WA

    2008-01-01

    Full Text Available Background: The prevalence and incidence of HCV infection varies geographically due to exposureto different risk factors. Identification of HCV genotype is important to defining the epidemiology of thedisease. The objective of this study was to describe genotype distribution and its relation to riskfactors among HCV infected patients attending virology clinic of the Department of InfectiousDiseases at the Tripoli Medical Centre. Methods: The medical records of 891 Libyan chronic HCVinfected patients registered and followed up from January 2003 to January 2007 were reviewed. Datagathered includes patient's age, gender, risk factors and family history of HCV infection. Statisticalanalysis was performed using t, x2 and contingency coefficient tests. Results: The mean age was40.22±13.09 years. Two thirds of patients were males. Normal alanine aminotransferase (ALT atdiagnosis was found in 62% of the patients. HCV RNA < 2 million copies at diagnosis was foundamong 54% of patients. HCV genotype 1 (G1 was the most frequent (30.9%, followed by G4(29.2%. Genotype 2 affected 19.3% and G3 13.6%. No classification of HCV genotype was availablefor 2% of the patients. Many subtypes of HCV were detected with different frequencies (G1a and b,G2a, b, c and a/c, G3a and G4a and c/d. All genotypes of HCV were more common among males(P<0.001. Genotype 3 was the most frequent among male patients (88.6%. Regarding the riskfactors, 33% of patients had a history of hospitalization and/or surgical procedures, and 22.7% had ahistory of blood transfusion. A past history of intravenous drug abuse (IVDA was reported by 15% ofthe patients, and 15.9% reported a history of dental procedures. The relationship between thegenotype of HCV and risk factors was statistically significant (P<0.001. No history of risky exposurewas found among 10.8% of patients. Conclusion: Genotypes 1 and 4 were more predominantamong HCV infected patients. Males were affected more than females and

  20. Molecular epidemiology of HIV, HBV, HCV, and HTLV-1/2 in drug abuser inmates in central Javan prisons, Indonesia.

    Science.gov (United States)

    Prasetyo, Afiono Agung; Dirgahayu, Paramasari; Sari, Yulia; Hudiyono, Hudiyono; Kageyama, Seiji

    2013-06-15

    This study was conducted to determine the current molecular prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and human T lymphotropic virus-1/2 (HTLV-1/2) circulating among drug abuser inmates incarcerated in prisons located in Central Java, Indonesia. Socio-epidemiological data and blood specimens were collected from 375 drug abuser inmates in four prisons. The blood samples were analyzed with serological and molecular testing for HIV, HBV, HCV, HDV, and HTLV-1/2. The seroprevalence of HIV, HBsAg, HCV, HDV, and HTLV-1/2 in drug abuser inmates was 4.8% (18/375), 3.2% (12/375), 34.1% (128/375), 0% (0/375), and 3.7% (14/375), respectively. No co-infections of HIV and HBV were found. Co-infections of HIV/HCV, HIV/HTLV-1/2, HBV/HCV, HBV/HTLV-1/2, and HCV/HTLV-1/2 were prevalent at rates of 4% (15/375), 1.3% (5/375), 1.1% (4/375), 0.3% (1/375), and 2.1% (8/375), respectively. The HIV/HCV co-infection rate was significantly higher in injection drug users (IDUs) compared to non-IDUs. Triple co-infection of HIV/HCV/HTLV-1/2 was found only in three IDUs (0.8%). HIV CRF01_AE was found to be circulating in the inmates. HBV genotype B3 predominated, followed by C1. Subtypes adw and adr were found. HCV genotype 1a predominated among HCV-infected inmates, followed by 1c, 3k, 3a, 4a, and 1b. All HTLV-1 isolates shared 100% homology with HTLV-1 isolated in Japan, while all of the HTLV-2 isolates were subtype 2a. Drug abuser inmates in prisons may offer a unique community to bridge prevention and control of human blood-borne virus infection to the general community.

  1. NS5A Sequence Heterogeneity and Mechanisms of Daclatasvir Resistance in Hepatitis C Virus Genotype 4 Infection.

    Science.gov (United States)

    Zhou, Nannan; Hernandez, Dennis; Ueland, Joseph; Yang, Xiaoyan; Yu, Fei; Sims, Karen; Yin, Philip D; McPhee, Fiona

    2016-01-15

    Daclatasvir is an NS5A inhibitor approved for treatment of infection due to hepatitis C virus (HCV) genotypes (GTs) 1-4. To support daclatasvir use in HCV genotype 4 infection, we examined a diverse genotype 4-infected population for HCV genotype 4 subtype prevalence, NS5A polymorphisms at residues associated with daclatasvir resistance (positions 28, 30, 31, or 93), and their effects on daclatasvir activity in vitro and clinically. We performed phylogenetic analysis of genotype 4 NS5A sequences from 186 clinical trial patients and 43 sequences from the European HCV database, and susceptibility analyses of NS5A polymorphisms and patient-derived NS5A sequences by using genotype 4 NS5A hybrid genotype 2a replicons. The clinical trial patients represented 14 genotype 4 subtypes; most prevalent were genotype 4a (55%) and genotype 4d (27%). Daclatasvir 50% effective concentrations for 10 patient-derived NS5A sequences representing diverse phylogenetic clusters were ≤0.080 nM. Most baseline sequences had ≥1 NS5A polymorphism at residues associated with daclatasvir resistance; however, only 3 patients (1.6%) had polymorphisms conferring ≥1000-fold daclatasvir resistance in vitro. Among 46 patients enrolled in daclatasvir trials, all 20 with baseline resistance polymorphisms achieved a sustained virologic response. Circulating genotype 4 subtypes are genetically diverse. Polymorphisms conferring high-level daclatasvir resistance in vitro are uncommon before therapy, and clinical data suggest that genotype 4 subtype and baseline polymorphisms have minimal impact on responses to daclatasvir-containing regimens. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  2. Rheumatoid Case with HCV Infection

    OpenAIRE

    Bita Behnava; Seyed-Moayed Alavian

    2005-01-01

    Case Presentation:A 46-year-old woman referred to our center due to abnormality in aminotransferase level during check up. She had a history of blood transfusion 12 years ago. Anti-HCV Ab by ELISA method and HCV RNA by RT-PCR were positive. HCV RNA by Amplicor HCV monitor test counted 800,000 IU/ml and the genotype was 3a by Specific Primer-Targeted Region Core method. Laboratory evaluation revealed: Hb 11.9 mg/dl, WBC 5000 /ml, platelet count 190,000/ ml, ALT 70 IU/ml, AST 65 IU/ml, Alk phos...

  3. Prevalence of non-organ-specific autoantibodies and chronic liver disease in the general population: a nested case-control study of the Dionysos cohort.

    Science.gov (United States)

    Lenzi, M; Bellentani, S; Saccoccio, G; Muratori, P; Masutti, F; Muratori, L; Cassani, F; Bianchi, F B; Tiribelli, C

    1999-09-01

    Several retrospective and prospective studies report an increased prevalence of non-organ-specific autoantibodies (NOSAs) in patients with hepatitis C virus (HCV) related chronic liver disease (CLD). Some of the data so far available are controversial and the true prevalence of NOSAs in the general population is still not known. To explore the prevalence of NOSAs, their relation to different HCV genotypes, and the presence and severity of CLD in the general population of Northern Italy. All 226 anti-HCV positive and 87 hepatitis B surface antigen (HBsAg) positive patients of the Dionysos cohort study were analysed and compared with sex and age matched cases (226) negative for both anti-HCV antibody and HBsAg selected from the same cohort. Sera tested for the presence of NOSAs (anti-nuclear antibody (ANA), anti-smooth muscle antibody (SMA), and anti-liver/kidney microsomes type 1 antibody (LKM1)) were screened by indirect immunofluorescence at a 1:40 serum dilution. HCV RNA and HCV genotypes were also determined by nested polymerase chain reaction (PCR) of the 5' non-coding region and by PCR amplification of the core region with type specific primers. The overall prevalence of NOSA reactivity was significantly higher in anti-HCV positive subjects than in both normal and pathological controls (25% v 6% and 7% respectively, pLKM1 occurred in 16, 10, and 1. 3% of cases respectively. No specific association between NOSAs and a specific HCV genotype was found. NOSAs were found more often associated with more than one genotype (35.7%) and with untypable genotypes (34.6%), although the association was not statistically significant. NOSAs were associated with HCV RNA and CLD but not with the presence of cirrhosis and/or hepatocellular carcinoma. On univariate analysis, NOSA reactivity was independently associated with abnormal alanine aminotransferase (p<0.01) and gamma-glutamyltranspeptidase levels (p<0.05). The risk for the presence of NOSAs was 5.1 times higher in anti-HCV

  4. Interferon lambda 4 (IFNL4 gene polymorphism is associated with spontaneous clearance of HCV in HIV-1 positive patients

    Directory of Open Access Journals (Sweden)

    Camila Fernanda da Silveira Alves

    Full Text Available Abstract Approximately one-third of the individuals infected with human immunodeficiency virus type 1 (HIV-1 are co-infected with hepatitis C virus (HCV. Co-infected patients have an increased risk for developing end-stage liver diseases. Variants upstream of the IFNL3 gene have been associated with spontaneous and treatment-induced clearance of HCV infection. Recently, a novel polymorphism was discovered, denoted IFNL4 ΔG > TT (rs368234815, which seems to be a better predictor of spontaneous clearance than the IFNL4 rs12979860 polymorphism. We aimed to determine the prevalence of the IFNL4 ΔG > TT variants and to evaluate the association with spontaneous clearance of HCV infection in Brazilian HIV-1 patients. The IFNL4 ΔG > TT genotypes were analyzed by polymerase chain reaction followed by restriction digestion in 138 HIV-1 positive patients who had an anti-HCV positive result. Spontaneous clearance of HCV was observed in 34 individuals (24.6%. IFNL4 genotype distribution was significantly different between individuals who had spontaneous clearance and chronic HCV patients (p=0.002. The probability of spontaneous clearance of HCV infection for patients with the IFNL4 TT/TT genotype was 3.6 times higher than for patients carrying the IFNL4 ΔG allele (OR=3.63, 95% CI:1.51-8.89, p=0.001. The IFNL4 ΔG > TT polymorphism seems to be better than IFNL4 rs12979860 to predict spontaneous clearance of the HCV in Brazilian HIV-1 positive patients.

  5.  Resistance-associated polymorphisms in Dutch hepatitis C genotype 1a patients with and without HIV infection.

    Science.gov (United States)

    Lieveld, Faydra I; Swaans, Niels; Newsum, Astrid M; Ho, Cynthia K Y; Schinkel, Janke; Molenkamp, Richard; van der Meer, Jan T M; Arends, Joop E; Hoepelman, Andy I M; Wensing, Anne M J; Siersema, Peter D; van Erpecum, Karel J; Boland, Greet J

    2016-01-01

     Background and aim. Resistance-associated variants (RAVs) on the NS3 region of the hepatitis C virus (HCV) may be relevant for antiviral therapy, but data in human immunodeficiency virus (HIV) coinfected patients are scarce. We assessed frequencies of NS3 RAVs in patients infected with HCV genotype 1a with or without HIV coinfection. HCV NS3 amino acids 1-181 were sequenced by the Sanger method and analyzed for RAVs. RAVs and their distribution between HCV genotype 1a clade I and II viruses were compared between HIV-infected versus HIV-uninfected patients. 148 samples were available (n = 68 HIV and n = 80 non-HIV). Relative frequency of clade I and clade II was significantly different between HIV (85% and 15%) and non-HIV groups (49% and 51%). Overall, HIV infected patients exhibited significantly lower prevalence of RAVs than HIV-uninfected patients (62% vs. 79%, p = 0.03). However, Q80K prevalence was significantly higher in HIV-infected subjects (50% vs. 24%, p = 0.001), whereas prevalence of S122D/G/N/S (2% vs. 16%, p = 0.002) and N174G/N/S (10% vs. 55%, p < 0.0001) polymorphisms were significantly lower. Q80K was found exclusively in clade I viruses. S122 (3% vs. 22%, p=0.001) and N174 (13% vs. 75%, p<0.0001) polymorphisms had significantly lower prevalence in clade I than clade II viruses. In the Netherlands, prevalence of clade I viruses and Q80K was significantly higher in HCV genotype 1a infected patients with HIV coinfection than in those without HIV coinfection. Prevalence of N174 and S122 polymorphisms was significantly higher in clade II than clade I viruses.

  6. HIV/HCV Coinfection in Taiwan.

    Science.gov (United States)

    Hsu, Ching-Sheng; Kao, Jia-Horng

    2016-01-01

    Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection are important global public health problems with shared transmission routes. Although HIV/HCV coinfection is not uncommon, the prevalence rates vary significantly across different studies and regions. In Taiwan, injection drug users have become the major contributors to the HIV/AIDS epidemic since 2005. Because the prevalence of HCV infection is high in injection drug users, this HIV epidemic is also associated with a significant increase of HIV/HCV coinfection in Taiwan. To control Taiwan's HIV epidemic, Taiwan Centers for Disease Control (CDC) launched a harm-reduction program in 2006. The HIV epidemic, the percentage attributed to injection drug users, and the prevalence of HIV/HCV coinfection gradually declined thereafter. In this article, we aimed to thoroughly examine the current literatures of HIV/HCV coinfection in Taiwan and hope to provide a better understanding of the needs for the management of this coinfection. We conducted a narrative review and searched for literature from PubMed, Ovid MEDLINE, and the Cochrane Library database untill August 2015. Studies relevant to the epidemiology and associated risk factors of HIV/HCV coinfection in Taiwan were examined and discussed.

  7. Genotype distribution and treatment response among incarcerated drug-dependent patients with chronic hepatitis C infection.

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    Chun-Han Cheng

    Full Text Available The prevalence of hepatitis C virus (HCV infection is disproportionately high among prisoners, especially among those who are drug-dependent. However, current screening and treatment recommendations are inconsistent for this population, and appropriate care is not reliably provided. To address these problems, the present study aimed to identify unique characteristics and clinical manifestations of incarcerated patients with HCV infection. We included incarcerated patients who received treatment with pegylated-interferon combined with ribavirin at Mackay Memorial Hospital in Taitung and were serving sentences at either the Taiyuan Skill Training Institute or the Yanwan Training Institute. HCV genotypes 1 (41.4%, 3 (25.9%, and 6 (24.1% were the most prevalent in the incarcerated patients. During the study period, we analyzed treatment response among 58 incarcerated patients and compared obtained results with treatment response among 52 patients who were living in the community. Higher sustained virological response rate was observed among patients with incarceration and HCV genotype other than 1. The odds ratios (corresponding 95% confidence intervals for incarceration and genotype 1 were 2.75 (1.06-7.11 and 0.37 (0.14-0.99, respectively. Better treatment compliance among incarcerated patients might partially explain these results. The results of this study suggest that treatment of prisoners with HCV infection is feasible and effective. More appropriate and timely methods are needed to prevent HCV transmission among injection drug users inside prisons.

  8. Direct anti-HCV agents

    Directory of Open Access Journals (Sweden)

    Xingquan Zhang

    2016-01-01

    Full Text Available Unlike human immunodeficiency virus (HIV and hepatitis B virus (HBV, hepatitis C virus (HCV infection is a curable disease. Current direct antiviral agent (DAA targets are focused on HCV NS3/4A protein (protease, NS5B protein (polymerase and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir (Sovaldi, simeprevir (Olysio, and fixed combination medicines Harvoni and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the “cure HCV” goal has become a reality. Concerns remain about drug resistance mutations and the high cost of these drugs. The investigation of new HCV drugs is progressing rapidly; fixed dose combination medicines in phase III clinical trials include Viekirax, asunaprevir+daclatasvir+beclabuvir, grazoprevir+elbasvir and others.

  9. Study of prevalence and effects of insulin resistance in patients with chronic hepatitis C genotype 4.

    Science.gov (United States)

    Amer, A F; Baddour, M M; Elshazly, M A; Fadally, G; Hanafi, N F; Assar, S L

    2016-02-01

    There is strong epidemiological evidence linking hepatitis C virus (HCV) infection and diabetes. Our aim was to evaluate the prevalence of insulin resistance in Egyptian patients with chronic HCV genotype 4 infection, to assess factors associated with insulin resistance and to test the impact of insulin resistance on outcomes of treatment with pegylated interferon/ribavirin. Insulin resistance [homeostasis model assessmentinsulin resistance (HOMA-IR) score > 3.0] was detected in 31 of 100 nondiabetic patients. The relationship between elevated HOMA-IR and baseline viral load and degree of fibrosis was statistically significant (r = 0.218 and r = 0.223). Follow-up of patients with complete early virological response until the end of treatment showed a statistically significant decrease in HOMA-IR score. Out of 29 liver tissue sections examined, 14 had a low level of expression of insulin receptor type 1 by immunohistochemical studies. This study confirms that insulin resistance affects treatment outcome, and thus HOMA-IR testing before initiation of therapy may be a cost-effective tool.

  10. No correlation between PNPLA3 rs738409 genotype and fatty liver and hepatic cirrhosis in Japanese patients with HCV.

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    Masato Nakamura

    Full Text Available BACKGROUND: Hepatitis C virus (HCV infection is associated with the development of cirrhosis and hepatocellular carcinoma and is also related to fatty change of the liver. Variation in patatin-like phospholipase domain-containing 3 (PNPLA3 gene is associated with disease progression in nonalcoholic fatty liver disease (NAFLD. Recent reports have suggested that PNPLA3, IL28B and TLR4-associated single nucleotide polymorphisms (SNPs may have an impact on hepatic steatosis or fibrosis in patients with chronic HCV infection. METHODS AND FINDINGS: Four SNPs (PNPLA3 rs738409, TLR4 rs4986790, TLR4 rs4986791, IL28B rs8099917 were identified in Japanese patients infected with HCV. We examined the association between the distribution of these SNP alleles and fatty change of the liver or existence of hepatic cirrhosis diagnosed by ultrasonography, one of the widely accessible and easy-to-use methods. PNPLA3 rs738409 G-allele and IL28B rs 8099917 minor allele were found in 70.0% and 31.1%, respectively. These two TLR4 SNPs were uniform in Japanese. Fatty change of the liver developed independent of the abscence of hepatic cirrhosis on sonographic findings and younger age. Hepatic cirrhosis was associated with a higher aspartate aminotransferase/platelet ratio index (APRI, no fatty change of the liver, higher BMI and higher AFP levels. No association between PNPLA3 rs738409/IL28B rs8099917 genotypes and hepatic steatosis or liver fibrosis was observed. CONCLUSIONS: According to ultrasound examinations, no association between PNPLA3 rs738409 genotype and fatty change of the liver or hepatic cirrhosis was found in Japanese patients infected with HCV. Together, our results suggested that the mechanism of hepatic steatosis underlying HCV infection might differ from that of NAFLD and should be explored.

  11. Hepatitis C Virus: Virology and Genotypes

    KAUST Repository

    Abdelaziz, Ahmed

    2017-12-01

    Hepatitis C virus (HCV) is a major causative agent of chronic liver disease worldwide. HCV is characterized by genetic heterogeneity, with at least six genotypes identified. The geographic distribution of genotypes has shown variations in different parts of the world over the past decade because of variations in population structure, immigration, and routes of transmission. Genotype differences are of epidemiologic interest and help the study of viral transmission dynamics to trace the source of HCV infection in a given population. HCV genotypes are also of considerable clinical importance because they affect response to antiviral therapy and represent a challenging obstacle for vaccine development.

  12. Prevalence and presentation of hepatitis B and C virus (HBV and HCV) infection in Vietnamese Americans via serial community serologic testing.

    Science.gov (United States)

    Nguyen, Kelvin; Van Nguyen, Thai; Shen, Duke; Xia, Victor; Tran, Diep; Banh, Khanh; Ruan, Victor; Hu, Ke-Qin

    2015-02-01

    The prevalence of hepatitis B virus (HBV) infection is reportedly high in Vietnamese Americans (VAs), but most previous studies did not assess full HBV serology, and not the prevalence of HBV and hepatitis C virus (HCV) infection simultaneously. The aim of the study is to assess the prevalence of different HBV serologies and HCV infection in VAs. This study was based on the data collected by testing for Hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibody (HBcAb IgG), anti-HBs antibody (HBsAb), and anti-HCV antibody (anti-HCV) in a series of community screening in VAs in Orange County, California. In 1,405 VA participants, the mean age was 51 (17-87) years, 45.1% were males; 68.2%, married; 97.2%, born in Vietnam. Most of the participants were non-US born with their primary language being non-English and with limited access to health care. Of the 1,405 cases, 124 (8.8%) were confirmed HBV infection by HBsAg+; 81 (5.8%), HCV infection by anti-HCV+; including four (0.3%) with HBV/HCV coinfection. Twelve percent of the participants with confirmed HBV infection thought they were previously tested negative, while 29.7% of the participants with confirmed HCV infection thought they were previously tested negative. In this cohort, 15.4% were HBsAg-/HBsAb-/HBcAb IgG-, i.e. being susceptible to HBV infection. In HCV infected participants, 65.4% were born between 1945 and 1965. This large serial survey and screening in the Vietnamese American community confirmed the rates of HBV and HCV infection to be as high as 8.8% and 5.8%, respectively. We have also identified factors related to HBV and HCV infection in this high-risk population.

  13. Performance comparison of new generation HCV core antigen test versus HCV RNA test in management of hepatitis C virus infection.

    Science.gov (United States)

    Çetiner, Salih; Çetin Duran, Alev; Kibar, Filiz; Yaman, Akgün

    2017-06-01

    The study has evaluated the performance of HCV core antigen (Cag) test by comparing HCV RNA PCR assay which is considered the gold standard for management of HCV infection. Totally, 132 samples sent for HCV RNA (real-time PCR) test were included in the study. Anti-HCV antibody test and HCV Cag test were performed by chemiluminescent enzyme immunoassay (CMEI). Anti-HCV test was positive in all samples. HCV RNA was detected in 112/132 (84.8%) samples, and HCV Cag in 105/132 (79.5%). The most common HCV genotype was genotype 1 (86%). Considering the HCV RNA test as gold standard; the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of Cag test were found to be 93.75%, 100%, 100%, 74.07% and 94.69%, respectively, and paired test results were detected as highly concordant. A high level of correlation was seen between HCV RNA and Cag tests, however, the concordance between the two tests appeared to be disrupted at viral loads lower than 10 3 IU/mL. On the contrary, the correlation reached significance for the values higher than 10 3 IU/mL. Viral loads were in the 17-2500IU/mL range for the negative results for Cag test. Pearson's correlation coefficient revealed a considerably high correlation. The concordance between HCV RNA and Cag tests was disrupted under a viral load lower than 10 3 IU/mL. Therefore, it would be appropriate to consider cost effectiveness, advantages and limitations of the HCV RNA and Cag tests during the decision on which method to use for patient management. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Molecular and epidemiological profiles of hepatitis C virus genotype 4 in Denmark

    DEFF Research Database (Denmark)

    Eriksen, Mette Brandt; Jørgensen, Louise Bruun; Krarup, Henrik

    2010-01-01

    The prevalence of hepatitis C virus (HCV) genotype 4 has increased throughout Europe. This is an epidemiological study of patients infected chronically with HCV genotype 4 in Denmark. The HCV strains analyzed originated from patient samples collected between 1999 and 2007 as part of the national...... patients (22%) were infected with subtypes 4h, 4k, 4l, 4n, 4o, or 4Unclassified. Three epidemiological profiles were identified: (1) patients infected with HCV by intravenous drug use were infected solely with subtype 4d. They were all of European origin, and 15 of the 16 patients were ethnic Danes....... No single transmission event could be confirmed, but the pairwise nucleotide identity within the patients of Danish origin was relatively high (~95%), suggesting a recent introduction into Denmark. (2) The 21 patients infected with subtype 4a all came from Northern Africa, Egypt, Pakistan, or the Middle...

  15. Prevalence of anelloviruses (TTV, TTMDV, and TTMV) in healthy blood donors and in patients infected with HBV or HCV in Qatar.

    Science.gov (United States)

    Al-Qahtani, Ahmed A; Alabsi, Enas S; AbuOdeh, Raed; Thalib, Lukman; El Zowalaty, Mohamed E; Nasrallah, Gheyath K

    2016-12-28

    Anelloviruses (TTV, TTMV, and TTMDV) have been associated with non A-G hepatitis. The goal of the current study was to estimate the prevalence of these anelloviruses in Qatar. A total of 607 blood samples (500 healthy donors, and 53 HBV-and 54 HCV-positive patients) representing different nationalities were tested for the presence of TTV, TTMV, and TTMDV DNA by nested PCR. Prevalence rates for the three viruses were high in all studied groups, and exceeding 95% in the HBV group (for TTV and TTMDV). Infection with more than one type of viruses was common and significant in most of the positive patients (p nationality, or gender (p > 0.05) albeit the detection of higher infection rates among females and Qatari subjects. This was the first published study to look at prevalence of Anellowviruses in the Middle East. High prevalence rates of the three viruses in all studied groups was noted. Further studies are needed to explore and compare the different genotypes of these viruses in the region.

  16. Prevalence of hepatitis C virus infection and associated factors among male illicit drug users in Cuiabá, Mato Grosso, Brazil

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    Antônia Carlos Magalhães Novais

    2009-09-01

    Full Text Available Intravenous drug injection has been reported as the main risk factor for hepatitis C virus (HCV infection. The aim of the present study was to describe the prevalence and the epidemiological profile of HCV infection among abusers of illegal injected and non-injected drugs in Cuiabá, state of Mato Grosso, Central Brazil. A cross-sectional study including 314 male drug users from eight detoxification centres was performed. Out of 314 subjects studied, 48 (15.2% were intravenous drug users. Participants were interviewed and had blood samples taken and tested for the presence of anti-HCV antibodies. Positive samples were tested for the presence of HCV RNA. Genotyping was performed on HCV RNA-positive samples. The overall prevalence of anti-HCV antibodies was 6.4% (n = 20. Out of 20 anti-HCV antibody-positive subjects, 16 (80% were also HCV RNA-positive. Genotype 1 predominated (75%, followed by 3a (25%. Subtype 1a was more common than 1b. HCV infection was more prevalent among intravenous drug users (33% than non-injecting users (1.5%. Logistic regression analyses showed independent associations between HCV infection and intravenous drug use, imprisonment and increasing age. In the present study, injecting drug use was the factor most strongly associated to HCV infection and inhaling or sniffing did not represent an increased susceptibility to infection.

  17. Prevalence of hepatitis C virus infection and associated factors among male illicit drug users in Cuiabá, Mato Grosso, Brazil.

    Science.gov (United States)

    Novais, Antônia Carlos Magalhães; Lopes, Carmen Luci Rodrigues; Reis, Nádia Rúbia da Silva; Silva, Agabo Macêdo Costa E; Martins, Regina Maria Bringel; Souto, Francisco José Dutra

    2009-09-01

    Intravenous drug injection has been reported as the main risk factor for hepatitis C virus (HCV) infection. The aim of the present study was to describe the prevalence and the epidemiological profile of HCV infection among abusers of illegal injected and non-injected drugs in Cuiabá, state of Mato Grosso, Central Brazil. A cross-sectional study including 314 male drug users from eight detoxification centres was performed. Out of 314 subjects studied, 48 (15.2%) were intravenous drug users. Participants were interviewed and had blood samples taken and tested for the presence of anti-HCV antibodies. Positive samples were tested for the presence of HCV RNA. Genotyping was performed on HCV RNA-positive samples. The overall prevalence of anti-HCV antibodies was 6.4% (n = 20). Out of 20 anti-HCV antibody-positive subjects, 16 (80%) were also HCV RNA-positive. Genotype 1 predominated (75%), followed by 3a (25%). Subtype 1a was more common than 1b. HCV infection was more prevalent among intravenous drug users (33%) than non-injecting users (1.5%). Logistic regression analyses showed independent associations between HCV infection and intravenous drug use, imprisonment and increasing age. In the present study, injecting drug use was the factor most strongly associated to HCV infection and inhaling or sniffing did not represent an increased susceptibility to infection.

  18. Hepatitis C virus in Vietnam: high prevalence of infection in dialysis and multi-transfused patients involving diverse and novel virus variants.

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    Linda Dunford

    Full Text Available Hepatitis C virus (HCV is a genetically diverse pathogen infecting approximately 2-3% of the world's population. Herein, we describe results of a large, multicentre serological and molecular epidemiological study cataloguing the prevalence and genetic diversity of HCV in five regions of Vietnam; Ha Noi, Hai Phong, Da Nang, Khanh Hoa and Can Tho. Individuals (n=8654 with varying risk factors for infection were analysed for the presence of HCV Ab/Ag and, in a subset of positive specimens, for HCV RNA levels (n=475 and genotype (n=282. In lower risk individuals, including voluntary blood donors, military recruits and pregnant women, the prevalence of infection was 0.5% (n=26/5250. Prevalence rates were significantly higher (p<0.001 in intravenous drug users (IDUs; 55.6%, n=556/1000, dialysis patients (26.6%, n=153/575 commercial sex workers (CSWs; 8.7%, n=87/1000, and recipients of multiple blood transfusions (6.0%, n=32/529. The prevalence of HCV in dialysis patients varied but remained high in all regions (11-43% and was associated with the receipt of blood transfusions [OR: 2.08 (1.85-2.34, p=0.001], time from first transfusion [OR: 1.07 (1.01-1.13, p=0.023], duration of dialysis [OR: 1.31 (1.19-1.43, p<0.001] and male gender [OR: 1.60 (1.06-2.41, p=0.026]. Phylogenetic analysis revealed high genetic diversity, particularly amongst dialysis and multi-transfused patients, identifying subtypes 1a (33%, 1b (27%, 2a (0.4%, 3a (0.7%, 3b (1.1%, 6a (18.8%, 6e (6.0%, 6h (4.6%, 6l (6.4% and 2 clusters of novel genotype 6 variants (2.1%. HCV genotype 1 predominated in Vietnam (60%, n=169/282 but the proportion of infections attributable to genotype 1 varied between regions and risk groups and, in the Southern part of Vietnam, genotype 6 viruses dominated in dialysis and multi-transfused patients (73.9%. This study confirms a high prevalence of HCV infection in Vietnamese IDUs and, notably, reveals high levels of HCV infection associated with dialysis and

  19. Distribution of Hepatitis C Virus Genotypes in the South Marmara Region

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    Harun Agca

    2014-03-01

    Full Text Available Aim: Hepatitis C virus (HCV is an important caustive agent of hepatitis, cirrhosis and hepatocellular carcinoma both in our country and the world. Prognosis and response to treatment is related with the genotype of HCV which has six genotypes and over a hundred quasispecies. Knowing the HCV genotype is also important for epidemiological data. In this study we aimed to investigate the HCV genotypes of samples sent to Uludag University Hospital Microbiology Laboratory which is the reference centre in the South Marmara Region. Material and Method: This study was done retrospectively to analyse the HCV patients%u2019 sera sent to our laboratory between July 2010and December 2012 for HCV genotyping. Artus HCV QS-RGQ PCR kit (Qiagene,Hilden, Germany was used in Rotor-Gene Q (Qiagene, Hilden Germany for detection of HCV RNA. HCV RNA positive samples of patients%u2019 sera were were used for genotyping by the Linear Array HCV genotyping test (Roche, NJ, USA.Results: 214 (92.6 % of total 231 patients included in the study were genotype 1, one (0.4 % was genotype 2, nine (3.9 % were genotype 3 and, seven (3.4 % were found genotype 4. Three of genotype 3 patients were of foreign nationality, two were born abroad and one of the genotype 4 patients were born abroad. Discussion: Concordant with our country data the most frequent genotype was 1, genotype 2 was seen in patients especially related with foreign countries and genotype 4 was seen rare. The importance of genotype 1, which is seen more frequent in our country and region is; resistance to antiviral treatment and prolonged treatment duration in chronic hepatitis C patients.

  20. A Cross Section Study to Determine the Prevalence of Antibodies against HIV Infection among Hepatitis B and C Infected Individuals

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    Geane L. Flores

    2016-03-01

    Full Text Available (1 Background: There are limited data regarding human immunodeficiency virus (HIV prevalence among hepatitis B virus (HBV or hepatitis C virus (HCV infected individuals. The aim of this cross-sectional study is to determine the prevalence of HBV and HCV infection among HIV individuals; (2 Methods: A total of 409 patients (126 HBV+ and 283 HCV+ referred to the Brazilian Reference Laboratory for Viral Hepatitis from 2010 to 2013 donated serum samples. Anti-HIV, HBsAg, anti-HBc, anti-HBs, anti-HBcIgM, anti-HBe, HBeAg, and anti-HCV antibodies were measured, and anti-HCV positive samples were tested for viral RNA and genotype; (3 Results: The anti-HIV antibody prevalence was 10.31% and 4.59% among HBV+ and HCV+ patients, respectively. The HCV mean (SD viral load was log 5.14 ± 1.64 IU/mL, and genotype I was most prevalent (163/283. Anti-HBs and anti-HBc were detected in 40% and 26% of HCV+ individuals, respectively. Among the HBV+ population, the presence of anti-HIV antibodies was associated with male gender, marital status (married, tattoo, sexual orientation, sexual practices (oral sex and anal sex, history of sexually transmitted diseases (STDs, history of viral hepatitis treatment, and a sexual partner with hepatitis or HIV. For the HCV+ group, the presence of anti-HIV antibodies was associated with female gender, marital status (married, anal intercourse, previous history of STDs, and number of sexual partners; (4 Conclusion: A high prevalence of anti-HIV antibodies was found among individuals with HBV and HCV, showing the importance of education programmes towards HIV infection among HBV- and HCV-infected individuals.

  1. Global prevalence and genotype distribution of hepatitis C virus infection in 2015

    DEFF Research Database (Denmark)

    2017-01-01

    BACKGROUND: The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national...... previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. FUNDING: John C Martin Foundation....... strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of-and expansion on-the 2014 analysis, which reported 80 million (95% CI 64-103) viraemic infections in 2013. METHODS: We developed country-level disease burden models following a systematic review of HCV...

  2. Prevalence of hepatitis C virus infection among recyclable waste collectors in Central-West Brazil.

    Science.gov (United States)

    Marinho, Thaís Augusto; Lopes, Carmen Luci Rodrigues; Teles, Sheila Araújo; Reis, Nádia Rúbia Silva; Carneiro, Megmar Aparecida dos Santos; de Andrade, Andreia Alves; Martins, Regina Maria Bringel

    2013-06-01

    The prevalence of hepatitis C virus (HCV) in a population of recyclable waste collectors (n = 431) was assessed using a cross-sectional survey in all 15 cooperatives in the city of Goiânia, Central-West Brazil. The HCV prevalence was 1.6% (95% confidence interval: 0.6-3.6) and a history of sexually transmitted infections was independently associated with this infection. HCV RNA (corresponding to genotype 1; subtypes 1a and 1b) was detected in five/seven anti-HCV-positive samples. Although the study population reported a high rate (47.3%) of sharps and needle accidents, HCV infection was not more frequent in recyclable waste collectors than in the general Brazilian population.

  3. Hepatitis C viral load, genotype 3 and interleukin-28B CC genotype predict mortality in HIV and hepatitis C-coinfected individuals

    DEFF Research Database (Denmark)

    Clausen, Louise Nygaard; Astvad, Karen; Ladelund, Steen

    2012-01-01

    OBJECTIVE: We hypothesized that hepatitis C virus (HCV) load and genotype may influence all-cause mortality in HIV-HCV-coinfected individuals. DESIGN AND METHODS: Observational prospective cohort study. Mortality rates were compared in a time-updated multivariate Poisson regression analysis....... RESULTS: We included 264 consecutive HIV-HCV-coinfected individuals. During 1143 person years at risk (PYR) 118 individuals died [overall mortality rate 10 (95% confidence interval; 8, 12)/100 PYR]. In multivariate analysis, a 1 log increase in HCV viral load was associated with a 30% higher mortality......) CC genotype was associated with 54% higher mortality risk [aMRR: 1.54 (0.89, 3.82] compared to TT genotype. CONCLUSION: High-HCV viral load, HCV genotype 3 and IL28B genotype CC had a significant influence on the risk of all-cause mortality among individuals coinfected with HIV-1. This may have...

  4. The history of hepatitis C virus (HCV)

    DEFF Research Database (Denmark)

    Bukh, Jens

    2016-01-01

    The discovery of hepatitis C virus (HCV) in 1989 permitted basic research to unravel critical components of a complex life cycle for this important human pathogen. HCV is a highly divergent group of viruses classified in 7 major genotypes and a great number of subtypes, and circulating in infected...

  5. Efficient hepatitis c virus genotype 1b core-NS5A recombinants permit efficacy testing of protease and NS5A inhibitors

    DEFF Research Database (Denmark)

    Pham, Long V.; Ramirez Almeida, Santseharay; Carlsen, Thomas H R

    2017-01-01

    Hepatitis C virus (HCV) strains belong to seven genotypes with numerous subtypes that respond differently to antiviral therapies. Genotype 1, and primarily subtype 1b, is the most prevalent genotype worldwide. The development of recombinant HCV infectious cell culture systems for different variants......, permitted by the high replication capacity of strain JFH1 (genotype 2a), has advanced efficacy and resistance testing of antivirals. However, efficient infectious JFH1-based cell cultures of subtype 1b are limited and comprise only the 5= untranslated region (5=UTR)-NS2, NS4A, or NS5A regions. Importantly...

  6. Continued high prevalence of HIV, HBV and HCV among injecting and noninjecting drug users in Italy

    Directory of Open Access Journals (Sweden)

    Laura Camoni

    2010-03-01

    Full Text Available We estimated the prevalence of HIV, HBV and HCV infections among injecting and non-injecting drug users treated within public drug-treatment centres in Italy to determine the correlates of infection. In the sample of 1330 drug users, the prevalence of HIV was 14.4% among drug injectors and 1.6% among non-injectors; the prevalence of HBV was 70.4% among injecting drug users and 22.8% among non-injectors and of HCV was 83.2% among injecting drug users and 22.0% among non-injectors. Old age, unemployment, and intravenous drug use were significantly correlated with each of the infections, as well as a longer history of injecting drug use. The results indicate that these infections continue to circulate among drug users, highlighting the need for monitoring of this group in Italy.

  7. Hepatitis C virus genotypes in Bahawalpur

    International Nuclear Information System (INIS)

    Qazi, M.A.; Fayyaz, M.; Chaudhry, G.M.D.; Jamil, A.

    2006-01-01

    This study was conducted at Medical Unit-II Bahawal Victoria Hospital / Quaid-e-Azam Medical College Bahawalpur from May 1st , 2005 to December 31st 2005. The objective of this study was to determine hepatitis C virus (HCV) genotypes in Bahawalpur, Pakistan. In consecutive 105 anti-HCV (ELISA-3) positive patients, complete history and physical examination was performed. Liver function tests, complete blood counts and platelet count, blood sugar fasting and 2 hours after breakfast, prothrombin time, serum albumin, serum globulin and abdominal ultrasound were carried out in all the patients. Tru cut biopsy was performed on 17 patients. We studied HCV RNA in all these patients by Nested PCR method. HCV RNA was detected in 98 patients and geno typing assay was done by genotype specific PCR. Among total of 105 anti-HCV positive patients, HCV-RNA was detected in 98 patients. Out of these 98 patients there were 57 (58.2%) males and 41 (42.8%) females. Their age range was 18-75 years. The age 18-29 years 26 (26.5%), 30-39 years 35 (35.7%) and 40-75 37 (37.8%), while 10 (10.2%) patients were diabetics and 34 (34.7%) patients were obese. Liver cirrhosis was present in 10 (10.2%) patients. Forty two (43.9%) patients were symptomatic while 56 (57.1%) were asymptomatic. Out of 98 patients 11 (11.2%) were un type-able and 87 (88.8%) were type able. 70/98 (71.4%) were genotype 3; 10/98 (10.2%) were genotype 1; 03/98 (3.1%) were genotype 2; 03/98 (3.1%) were mixed genotype 2 and 3; 01/98 (1%) were mixed genotype 3a and 3b. Genotype 3 is the most common HCV virus in our area which shows that both virological and biochemical response will be better. Because HCV genotype 3 is more frequent among the drug users which points towards unsafe injection practices in our area. (author)

  8. Efficient infectious cell culture systems of the hepatitis C virus (HCV) prototype strains HCV-1 and H77

    DEFF Research Database (Denmark)

    Li, Yi-Ping; Ramirez, Santseharay; Mikkelsen, Lotte

    2015-01-01

    UNLABELLED: The first discovered and sequenced hepatitis C virus (HCV) genome and the first in vivo infectious HCV clones originated from the HCV prototype strains HCV-1 and H77, respectively, both widely used in research of this important human pathogen. In the present study, we developed...... efficiently after transfection and subsequent infection of naive Huh7.5 cells, reaching titers of 10(3.5) and 10(4.4) FFU/ml, respectively. IMPORTANCE: Hepatitis C virus (HCV) was discovered in 1989 with the cloning of the prototype strain HCV-1 genome. In 1997, two molecular clones of H77, the other HCV...... prototype strain, were shown to be infectious in chimpanzees, but not in vitro. HCV research was hampered by a lack of infectious cell culture systems, which became available only in 2005 with the discovery of JFH1 (genotype 2a), a genome that could establish infection in Huh7.5 cells. Recently, we...

  9. Formal hepatitis C education enhances HCV care coordination, expedites HCV treatment and improves antiviral response.

    Science.gov (United States)

    Lubega, Samali; Agbim, Uchenna; Surjadi, Miranda; Mahoney, Megan; Khalili, Mandana

    2013-08-01

    Formal Hepatitis C virus (HCV) education improves HCV knowledge but the impact on treatment uptake and outcome is not well described. We aimed to evaluate the impact of formal HCV patient education on primary provider-specialist HCV comanagement and treatment. Primary care providers within the San Francisco safety-net health care system were surveyed and the records of HCV-infected patients before and after institution of a formal HCV education class by liver specialty (2006-2011) were reviewed retrospectively. Characteristics of 118 patients who received anti-HCV therapy were: mean age 51, 73% males and ~50% White and uninsured. The time to initiation of HCV treatment was shorter among those who received formal education (median 136 vs 284 days, P non-1 genotype (OR 6.17, 95% CI 2.3-12.7, P = 0.0003) and receipt of HCV education (OR 3.0, 95% CI 1.1-7.9, P = 0.03) were associated with sustained virologic treatment response. Among 94 provider respondents (response rate = 38%), mean age was 42, 62% were White, and 63% female. Most providers agreed that the HCV education class increased patients' HCV knowledge (70%), interest in HCV treatment (52%), and provider-patient communication (56%). A positive provider attitude (Coef 1.5, 95% CI 0.1-2.9 percent, P = 0.039) was independently associated with referral rate to education class. Formal HCV education expedites HCV therapy and improves virologic response rates. As primary care provider attitude plays a significant role in referral to HCV education class, improving provider knowledge will likely enhance access to HCV specialty services in the vulnerable population. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Hepatitis B and hepatitis C viruses: a review of viral genomes, viral induced host immune responses, genotypic distributions and worldwide epidemiology

    Directory of Open Access Journals (Sweden)

    Umar Saeed

    2014-04-01

    Full Text Available Hepatitis B and hepatitis C viruses (HCV are frequently propagating blood borne pathogens in global community. Viral hepatitis is primarily associated with severe health complications, such as liver cirrhosis, hepatocellular carcinoma, hepatic fibrosis and steatosis. A literature review was conducted on hepatitis B virus (HBV, HBV genome, genotypic distribution and global epidemiology of HBV, HCV, HCV genome, HCV and host immune responses, HCV genotypic distribution and global epidemiology. The valued information was subjected for review. HBV has strict tissue tropism to liver. The virus infecting hepatocytes produces large amount of hepatitis B surface antigen particles which lack the DNA. It has capability to integrate into host genome. It has been found that genotype C is most emerging genotype associated with more severe liver diseases (cirrhosis. The approximate prevalence rate of genotype C is 27.7% which represents a major threat to future generations. Approximately 8% of population is chronic carrier of HBV in developing countries. The chronic carrier rate of HBV is 2%-7% in Middle East, Eastern and Southern Europe, South America and Japan. Among HCV infected individuals, 15% usually have natural tendency to overcome acute viral infection, where as 85% of individuals were unable to control HCV infection. The internal ribosomal entry site contains highly conserved structures important for binding and appropriate positioning of viral genome inside the host cell. HCV infects only in 1%-10% of hepatocytes, but production of tumor necrosis factor alpha (from CD8+ cells and interferon-gamma cause destruction of both infected cells and non-infected surrounding cells. Almost 11 genotypes and above 100 subtypes of HCV exists worldwide with different geographical distribution. Many efforts are still needed to minimize global burden of these infections. For the complete eradication of HBV (just like small pox and polio via vaccination strategies

  11. Core Gene Expression and Association of Genotypes with Viral ...

    African Journals Online (AJOL)

    Purpose: To determine genotypic distribution, ribonucleic acid (RNA) RNA viral load and express core gene from Hepatitis C Virus (HCV) infected patients in Punjab, Pakistan. Methods: A total of 1690 HCV RNA positive patients were included in the study. HCV genotyping was tested by type-specific genotyping assay, viral ...

  12. The HCV Synthesis Project: Scope, methodology, and preliminary results

    Directory of Open Access Journals (Sweden)

    Scheinmann Roberta

    2008-09-01

    Full Text Available Abstract Background The hepatitis C virus (HCV is hyper-endemic in injecting drug users. There is also excess HCV among non-injection drug users who smoke, snort, or sniff heroin, cocaine, crack, or methamphetamine. Methods To summarize the research literature on HCV in drug users and identify gaps in knowledge, we conducted a synthesis of the relevant research carried out between 1989 and 2006. Using rigorous search methods, we identified and extracted data from published and unpublished reports of HCV among drug users. We designed a quality assurance system to ensure accuracy and consistency in all phases of the project. We also created a set of items to assess study design quality in each of the reports we included. Results We identified 629 reports containing HCV prevalence rates, incidence rates and/or genotype distribution among injecting or non-injecting drug user populations published between January 1989 and December 2006. The majority of reports were from Western Europe (41%, North America (26%, Asia (11% and Australia/New Zealand (10%. We also identified reports from Eastern Europe, South America, the Middle East, and the Caribbean. The number of publications reporting HCV rates in drug users increased dramatically between 1989 and 2006 to 27–52 reports per year after 1998. Conclusion The data collection and quality assurance phases of the HCV Synthesis Project have been completed. Recommendations for future research on HCV in drug users have come out of our data collection phase. Future research reports can enhance their contributions to our understanding of HCV etiology by clearly defining their drug user participants with respect to type of drug and route of administration. Further, the use of standard reporting methods for risk factors would enable data to be combined across a larger set of studies; this is especially important for HCV seroconversion studies which suffer from small sample sizes and low power to examine risk

  13. Evaluation of the immunogenicity of liposome encapsulated HVR1 and NS3 regions of genotype 3 HCV, either singly or in combination

    Directory of Open Access Journals (Sweden)

    Gupte Gouri M

    2012-03-01

    Full Text Available Abstract Background Hepatitis C virus displays a high rate of mutation and exists as a quasispecies in infected patients. In the absence of an effective universal vaccine, genotype-specific vaccine development represents an alternative. We have attempted to develop a genotype 3 based, liposome encapsulated HCV vaccine with hypervariable region-1 (HVR1 and non-structural region-3 (NS3 components. Results HCV RNA extracted from serum samples of 49 chronically infected patients was PCR amplified to obtain HVR1 region. These amplified products were cloned to obtain 20 clones per sample in order to identify the quasispecies pattern. The HVR1 consensus sequence, along with three variants was reverse transcribed to obtain peptides. The peptides were checked for immunoreactivity individually, as a pool or as a single peptide tetramer interspersed with four glycine residues. Anti-HCV positivity varied from 42.6% (tetramer to 92.2% (variant-4 when 115 anti-HCV positive sera representing genotypes 1, 3, 4 and 6 were screened. All the 95 anti-HCV negatives were scored negative by all antigens. Mice were immunized with different liposome encapsulated or Al(OH3 adjuvanted formulations of HVR1 variants and recombinant NS3 protein, and monitored for anti-HVR1 and anti-NS3 antibody titres, IgG isotypes and antigen specific cytokine levels. A balanced Th1/Th2 isotyping response with high antibody titres was observed in most of the liposome encapsulated antigen groups. The effect of liposomes and aluminium hydroxide on the expression of immune response genes was studied using Taqman Low Density Array. Both Th1 (IFN-gamma, Il18 and Th2 (Il4 genes were up regulated in the liposome encapsulated HVR1 variant pool-NS3 combination group. In-vitro binding of the virus to anti-HVR1 antibodies was demonstrated. Conclusion The optimum immunogen was identified to be combination of peptides of HVR1 consensus sequence and its variants along with pNS3 encapsulated in liposomes

  14. Naturally occurring hepatitis C virus protease inhibitors resistance-associated mutations among chronic hepatitis C genotype 1b patients with or without HIV co-infection.

    Science.gov (United States)

    Cao, Ying; Zhang, Yu; Bao, Yi; Zhang, Renwen; Zhang, Xiaxia; Xia, Wei; Wu, Hao; Xu, Xiaoyuan

    2016-05-01

    The aim of this study was to measure the frequency of natural mutations in hepatitis C virus (HCV) mono-infected and HIV/HCV co-infected protease inhibitor (PI)-naive patients. Population sequence of the non-structural (NS)3 protease gene was evaluated in 90 HCV mono-infected and 96 HIV/HCV co-infected PI treatment-naive patients. The natural prevalence of PI resistance mutations in both groups was compared. Complete HCV genotype 1b NS3 sequence information was obtained for 152 (81.72%) samples. Seven sequences (8.33%) of the 84 HCV mono-infected patients and 21 sequences (30.88%) of the 68 HIV/HCV co-infected patients showed amino acid substitutions associated with HCV PI resistance. There was a significant difference in the natural prevalence of PI resistance mutations between these two groups (P = 0.000). The mutations T54S, R117H and N174F were observed in 1.19%, 5.95% and 1.19% of HCV mono-infected patients. The mutations F43S, T54S, Q80K/R, R155K, A156G/V, D168A/E/G and V170A were found in 1.47%, 4.41%, 1.47%/1.47%, 2.94%, 23.53%/1.47%, 1.47%/1.47%/1.47% and 1.47% of HIV/HCV co-infected patients, respectively. In addition, the combination mutations in the NS3 region were detected only in HIV/HCV genotype 1b co-infected patients. Naturally occurring HCV PI resistance mutations existed in HCV mono-infected and HIV/HCV co-infected genotype 1b PI-naive patients. HIV co-infection was associated with a greater frequency of PI resistance mutations. The impact of HIV infection on baseline HCV PI resistance mutations and treatment outcome in chronic hepatitis C (CHC) patients should be further analyzed. © 2015 The Japan Society of Hepatology.

  15. Humanized-VHH Transbodies that Inhibit HCV Protease and Replication

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    Surasak Jittavisutthikul

    2015-04-01

    Full Text Available There is a need for safe and broadly effective anti-HCV agents that can cope with genetic multiplicity and mutations of the virus. In this study, humanized-camel VHHs to genotype 3a HCV serine protease were produced and were linked molecularly to a cell penetrating peptide, penetratin (PEN. Human hepatic (Huh7 cells transfected with the JFH-1 RNA of HCV genotype 2a and treated with the cell penetrable nanobodies (transbodies had a marked reduction of the HCV RNA intracellularly and in their culture fluids, less HCV foci inside the cells and less amounts of HCV core antigen in culture supernatants compared with the infected cells cultured in the medium alone. The PEN-VHH-treated-transfected cells also had up-regulation of the genes coding for the host innate immune response (TRIF, TRAF3, IRF3, IL-28B and IFN-β, indicating that the cell penetrable nanobodies rescued the host innate immune response from the HCV mediated-suppression. Computerized intermolecular docking revealed that the VHHs bound to residues of the protease catalytic triad, oxyanion loop and/or the NS3 N-terminal portion important for non-covalent binding of the NS4A protease cofactor protein. The so-produced transbodies have high potential for testing further as a candidate for safe, broadly effective and virus mutation tolerable anti-HCV agents.

  16. Chronic hepatitis c genotype-4 infection: role of insulin resistance in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    M Hashem Abdel

    2011-11-01

    Full Text Available Abstract Background Hepatitis C virus (HCV is a major cause of chronic hepatitis and hepatocellular carcinoma (HCC and different HCV genotypes show characteristic variations in their pathological properties. Insulin resistance (IR occurs early in HCV infection and may synergize with viral hepatitis in HCC development. Egypt has the highest reported rates of HCV infection (predominantly genotype 4 in the world; this study investigated effects of HCV genotype-4 (HCV-4 on prevalence of insulin resistance in chronic hepatitis C (CHC and HCC in Egyptian patients. Methods Fifty CHC patients, 50 HCC patients and 20 normal subjects were studied. IR was estimated using HOMA-IR index and HCV-4 load determined using real-time polymerase chain reaction. Hepatitis B virus was excluded by enzyme-linked immunosorbent assay. Standard laboratory and histopathological investigations were undertaken to characterize liver function and for grading and staging of CHC; HCC staging was undertaken using intraoperative samples. Results HCC patients showed higher IR frequency but without significant difference from CHC (52% vs 40%, p = 0.23. Multivariate logistic regression analysis showed HOMA-IR index and International Normalization Ratio independently associated with fibrosis in CHC; in HCC, HbA1c, cholesterol and bilirubin were independently associated with fibrosis. Fasting insulin and cholesterol levels were independently associated with obesity in both CHC and HCC groups. Moderate and high viral load was associated with high HOMA-IR in CHC and HCC (p Conclusions IR is induced by HCV-4 irrespective of severity of liver disease. IR starts early in infection and facilitates progression of hepatic fibrosis and HCC development.

  17. Hepatitis C Virus: Virology and Genotypes

    KAUST Repository

    Abdelaziz, Ahmed

    2017-01-01

    Hepatitis C virus (HCV) is a major causative agent of chronic liver disease worldwide. HCV is characterized by genetic heterogeneity, with at least six genotypes identified. The geographic distribution of genotypes has shown variations in different

  18. Point -of -care testing (POCT) in molecular diagnostics: Performance evaluation of GeneXpert HCV RNA test in diagnosing and monitoring of HCV infection.

    Science.gov (United States)

    Gupta, Ekta; Agarwala, Pragya; Kumar, Guresh; Maiwall, Rakhi; Sarin, Shiv Kumar

    2017-03-01

    Molecular testing at the point-of-care may turn out to be game changer for HCV diagnosis and treatment monitoring, through increased sensitivity, reduced turnaround time, and ease of performance. One such assay GeneXpert ® has recently been released. Comparative analysis between performances of GeneXpert ® and Abbott HCV-RNA was done. 174 HCV infected patients were recruited and, one time plasma samples from 154 patients and repeated samples from 20 patients, obtained at specific treatment time-points (0, 4, 12 and 24) weeks were serially re-tested on Xpert ® . Genotype 3 was the commonest, seen in 80 (66%) of the cases, genotype 1 in 34 (28.3%), genotype 4 in 4 (3.3%) and genotypes 2 and 5 in 1 (0.8%) each. Median HCV RNA load was 4.69 log 10 (range: 0-6.98log 10 ) IU/ml. Overall a very good correlation was seen between the two assays (R 2 =0.985), concordance of the results between the assays was seen in 138 samples (89.6%). High and low positive standards were tested ten times on Xpert ® to evaluate the precision and the coefficient of variation was 0.01 for HPC and 0.07 for the LPC. Monitoring of patients on two different regimes of treatment, pegylated interferon plus ribavirin and sofosbuvir plus ribavirin was done by both the systems at baseline, 4, 12 and 24 weeks. Perfect correlation between the assays in the course of therapy at different treatment time- point in genotypes 3 and 1 was seen. The study demonstrates excellent performance of the Xpert ® HCV assay in viral load assessment and in treatment course monitoring consistency. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Resistance Patterns Associated with HCV NS5A Inhibitors Provide Limited Insight into Drug Binding

    Directory of Open Access Journals (Sweden)

    Moheshwarnath Issur

    2014-11-01

    Full Text Available Direct-acting antivirals (DAAs have significantly improved the treatment of infection with the hepatitis C virus. A promising class of novel antiviral agents targets the HCV NS5A protein. The high potency and broad genotypic coverage are favorable properties. NS5A inhibitors are currently assessed in advanced clinical trials in combination with viral polymerase inhibitors and/or viral protease inhibitors. However, the clinical use of NS5A inhibitors is also associated with new challenges. HCV variants with decreased susceptibility to these drugs can emerge and compromise therapy. In this review, we discuss resistance patterns in NS5A with focus prevalence and implications for inhibitor binding.

  20. Epidemiological manifestations of hepatitis C virus genotypes and its association with potential risk factors among Libyan patients.

    Science.gov (United States)

    Elasifer, Hana A; Agnnyia, Yossif M; Al-Alagi, Basher A; Daw, Mohamed A

    2010-11-13

    The information on hepatitis C virus genotypes and subtypes among Libyan population and its association with various risk factors is not known. The objectives of this study were to determine the epidemiological manifestations of HCV genotypes among Libyan patients and their association with certain potential risk factors. A total of 1240 of HCV infected patients registered at Tripoli Medical Centre were studied in five years period from January 2005 to October 2009. The information were reviewed and the data were collected. A sample from each patient (785 male; 455 female) was analysed for genotyping and sub-typing using specific genotyping assay. The information was correlated with the risk factors studied and the statistical data were analyzed using SPSS version 11.5. Off the total patients studied, four different genotypes were reported, including genotypes 1, 2, 3, and 4. Genotype4 was the commonest (35.7%), followed by genotype1 (32.6%). According to subtypes 28% were unclassified genotype 4, 14.6% were genotype 1b and some patients infected with more than one subtype (2.3% genotype 4c/d, 1% genotype 2a/c). Genotypes 1 was the commonest among males, while genotype 4 among females. According to the risk factors studied, Genotype1 and genotype 4 were found with most of the risk factors. Though they were particularly evident surgical intervention, dental procedures and blood transfusion while genotype 1 was only followed by genotype 3 mainly which mainly associated with certain risk groups such as intravenous drug abusers. Here in we report on a detailed description of HCV genotype among Libyans. The most common genotype was type 4 followed by genotype 1, other genotypes were also reported at a low rate. The distribution of such genotypes were also variable according to gender and age. The commonly prevalent genotypes found to be attributable to the medical -related transmission of HCV, such as blood, surgery and dental procedures when compared with other risk

  1. HBV or HCV Coinfection in HIV-1-Infected Pregnant Women in France: Prevalence and Pregnancy Outcomes.

    Science.gov (United States)

    Benhammou, Valérie; Tubiana, Roland; Matheron, Sophie; Sellier, Pierre; Mandelbrot, Laurent; Chenadec, Jérôme Le; Marel, Emmanuelle; Khoshnood, Babak; Warszawski, Josiane

    2018-04-15

    Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is frequent in HIV-infected persons but their impact on pregnant HIV-infected women is understudied. We explored whether these coinfections are associated with adverse pregnancy outcomes and lower response to antiretroviral therapy (ART). Pregnancies in HIV-1-infected women included in the ANRS French Perinatal Cohort between 2005 and 2013 were analyzed if HBV and HCV infection statuses were available. Among 4236 women, the prevalence of HBV (HBs Ag+) and HCV (RNA+) were 6.2% (95% confidence interval: 5.4 to 6.8) and 1.7% (1.3 to 2.1), respectively. HCV coinfection was strongly associated with a history of drug use; HBV coinfection was 6 times more frequent in women born in Sub-Saharan Africa than in European France. Baseline HIV viral load, CD4 count, and HIV care during pregnancy were similar in coinfected and monoinfected HIV mothers, except that 90% of HBV/HIV women were receiving tenofovir and/or lamivudine or emtricitabine. HCV coinfection was significantly associated with cholestasis [adjusted odds ratio: 4.1 (1.5-10.8), P = 0.005], preterm delivery [3.0 (1.6-5.7), P HIV-infected women, chronic HBV infection, mostly treated using targeted ART, had no major impact on the course of pregnancy. By contrast, chronic HCV infection was associated with a higher risk of obstetrical complications and a poorer immune-virological response to ART. It is yet unknown whether cure of HCV infection before conception can limit these adverse outcomes.

  2. Hepatitis C Prevalence and Responses to Pegylated Interferon + Ribavirin Treatment Among Prisoners

    Directory of Open Access Journals (Sweden)

    Hasan Selçuk ÖZGER

    2017-12-01

    Full Text Available Objective: The aim of our study was to identify the hepatitis C prevalence in prisoners and to share experiences of pegylated interferon (peg-IFN + ribavirin (RBV treatment. Materials and Methods: The study was conducted by assessing the records of prisoners between January 2014 and 2016, retrospectively. Patients in whom planned treatments were applied in a given time were determined and, virologic responses at the end of treatment and 6 months after treatment were evaluated. Chi-square test was used and a p value of less than 0.05 was considered statistically significant. Results: Among prisoners, the anti-hepatitis C virus (HCV positivity rate was 7.82% and HCV-RNA positivity rate was 5.72%. The most common genotype was genotype 3a (66 of 99 patients. End-of-treatment and 6th month sustained virologic response rates were 84.6% and 80.5%, respectively. In genotype 3a group, end-of-treatment and 6th month sustained virologic response rates were found to be higher than other genotypes but not statistically significant. Conclusion: In our study, which assessed prisoners, the rate of HCV positivity was higher than hepatitis C in the general population in Turkey. In accordance with the literature, genotype 3 was the most common genotype among prisoners. Sustained virologic response rates obtained with peg-IFN+RBV treatment suggested that peg-IFN treatment should be used with current treatment combinations in prisoners infected with HCV genotype 3.

  3. Seroprevalence, genotypic distribution and potential risk factors of hepatitis B and C virus infections among adults in Siem Reap, Cambodia.

    Science.gov (United States)

    Yamada, Hiroko; Fujimoto, Mayumi; Svay, Somana; Lim, Olline; Hok, Sirany; Goto, Noboru; Ohisa, Masayuki; Akita, Tomoyuki; Matsuo, Junko; Do, Son Huy; Katayama, Keiko; Miyakawa, Yuzo; Tanaka, Junko

    2015-04-01

    We investigated hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among adults in Siem Reap, Cambodia, to consider the prevention strategy in cooperation with the Ministry of Health in Cambodia. Serological tests for determining HBV and HCV infections and questionnaires were performed from 2010 to 2012 among the general population in the province of Siem Reap. Multivariate logistic regression analysis was conducted to clarify the factors related to HBV and HCV infections. There were 483 participants, comprising 194 men and 289 women (age range, 18-89 years). The prevalence of hepatitis B surface antigen was not very high at 4.6%, while anti-hepatitis B core (anti-HBc) was high at 38.5%. All HBV DNA samples were classified as genotype C. Anti-HBc showed the trend that the older the age, the higher the positive rate (P = 0.0002). The prevalence of HCV RNA and anti-HCV were 2.3% and 5.8%, respectively. HCV RNA was detected in 39.3% of anti-HCV positive samples and most of them were classified as genotype 6 (54.5%) and 1 (27.3%). Remarkably, in multivariate logistic regression analysis, history of operation and blood transfusion were significantly associated with the positivity for HBV infection and HCV RNA, respectively. Our results showed that operation and blood transfusion were potential risk factors for HBV and HCV infection, respectively, and supposed that horizontal HBV transmission may be frequent in adults in Cambodia. Hence, for reducing HBV and HCV infections, it is necessary to improve the safety of blood and medical treatment. © 2014 The Japan Society of Hepatology.

  4. Changes in epidemiological patterns of HCV infection and their impact on liver disease over the last 20 years in Greece.

    Science.gov (United States)

    Savvas, S P; Koskinas, J; Sinani, C; Hadziyannis, A; Spanou, F; Hadziyannis, S J

    2005-09-01

    The aim of this study was to investigate the relative frequency of hepatitis C virus (HCV) genotypes in Greek patients with chronic infection as well as possible secular changes in their distribution in relation to modes of transmission, age and time at acquisition of the infection and other variables. We evaluated 434 unselected patients, 241 males and 193 females with a median age of 46.2 years (18-75), with chronic HCV infection presenting during the period 1996-2000. HCV infection was confirmed by the detection of HCV-RNA by polymerase chain reaction (PCR), while HCV genotyping was performed by the Inno-LiPA assay. Liver biopsies were evaluated according to Ishak's scoring system. Of 434 patients, 167 had a history of blood transfusion [post-transfusion hepatitis (PTH)], 80 were i.v. drug users and in 187 the route of infection remained unknown. The overall distribution of HCV genotypes 1, 2, 3 and 4 was 47, 8.3, 27 and 15.2%, respectively. Genotype 3 was common in younger adults and i.v. drug users, whereas genotype 1 predominated in older people and PTH patients (P duration of infection (P = 0.013). Our study revealed a change of HCV genotype distribution in the last 20 years among Greek patients with chronic HCV infection as a result of epidemiological changes in HCV transmission. The presence of cirrhosis was associated only with the duration of infection. These observations have impact both on prevention and treatment.

  5. Role of ribavirin in HCV treatment response: now and in the future.

    Science.gov (United States)

    Jain, Mamta K; Zoellner, Cindy

    2010-03-01

    Ribavirin is a broad spectrum antiviral agent that is used with pegylated IFN (Peg-IFN) for HCV treatment. Ribavirin does not significantly reduce HCV viral load when used alone but increases rates of sustained virologic response (SVR) when combined with Peg-IFN. HCV genotype 1 infected patients require higher doses of ribavirin administered for a longer duration of time versus HCV genotypes 2 and 3 patients who respond effectively to Peg-IFN with lower doses of ribavirin and shorter duration of therapy. Higher serum concentrations of ribavirin are associated with higher response rates but also higher rates of hemolytic anemia which is a dose limiting side effect. Alternatives to current therapy are under clinical evaluation. Systematic literature review of ribavirin use in HCV patients from 1995 to 2009 was conducted. To review the efficacy and safety of ribavirin in current HCV treatment and in new therapies in Phase III clinical trials. Ribavirin is a drug which is essential to produce higher SVR rates both with Peg-IFN and HCV protease inhibitors currently in Phase III clinical trials. Thus, ribavirin is and will remain an important drug to achieving higher SVR rates in HCV infected persons.

  6. Hepatitis C virus Genotypes in Patients with End-Stage Renal Disease in East Azerbaijan, Iran

    Directory of Open Access Journals (Sweden)

    Somi Mohammad

    2008-01-01

    Full Text Available Information about the genotypes and associated risk factors in hepatitis C virus (HCV infected patients in Iran is limited. The aim of this study was to identify the HCV genotypes and associated risk factors in a group of HCV infected patients on dialysis therapy in Iran. The sera of 753 patients with chronic renal failure from fifteen dialysis units in East Azerbaijan Province were screened for anti-HCV antibodies as well as HCV RNA; viral RNA was extracted for the genotype specific primer approach. Patients were questioned concerning documented risk factors. Genotyping analysis was performed in 55 patients with positive anti-HCV and HCV-RNA. Genotypes 1 and 3 were found in 46 (83.7% and three (5.5% patients, respectively. The most frequent HCV subtype was 1a (76.4%, followed by 3a and 1b and 1b (5.5% each while one patient was infected with both 1a and 1b. There was no statistically significant difference between the risk factors analyzed and the acqui-sition of HCV infection. This study gives added evidence of the predominant HCV genotypes in Iran, which is different than reports from other Arab countries and similar with the pattern of genotype in both Europe and United States.

  7. Usefulness of Dried Blood Spots (DBS) to perform hepatitis C virus genotyping in drug users in Senegal.

    Science.gov (United States)

    Ndiaye, O; Gozlan, J; Diop-Ndiaye, H; Sall, A S; Chapelain, S; Leprêtre, A; Maynart, M; Gueye, M; Lo, G; Thiam, M; Ba, I; Lacombe, K; Girard, P M; Mboup, S; Kane, C T

    2017-03-01

    The aim of this pilot study was to analyze the Hepatitis C Virus (HCV) genotypes circulating in Senegal among Drug User (DUs), using Dried Blood Spots (DBS) as RNA source for molecular assays. Heroin and/or cocaine users (n = 506) were recruited in Dakar from April to July 2011, using a Respondent Driven Sampling (RDS) method. DBS preparation consisted of five drops of whole blood from finger applied to a Whatman paper card. HCV infection was screened by the detection of anti-HCV antibodies, using a rapid immune-chromatographic test. HCV RNA was quantified on anti-HCV positive DBS, using the Abbott RealTime HCV® Genotyping was performed on DBS with detectable viral load with Versant® HCV Genotype 2.0 Assay (LiPA) and Abbott RealTime HCV Genotype II assay®. Among the 506 participants, 120 were tested as positive for anti-HCV antibodies and their samples were analyzed for HCV RNA viral load and genotype. Out of the 120 DBS tested, HCV RNA was detected on 25 (20.8%). The median viral load was 15,058 IU/ml (ranging from 710 to 766,740 IU/ml). All positive DBS were suitable for the genotyping assay, that showed a predominance of genotype 1 (21/25) including 16 genotypes 1a and 5 genotypes 1b. HCV genotype 1 prevails in a DU population in Dakar. DBS could be useful for HCV RNA genotyping, but optimal storage conditions should required avoiding RNA impairment. Acknowledging this limitation, DBS could be a great interest for detecting and genotyping HCV viremic patients. J. Med. Virol. 89:484-488, 2017. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  8. Identification of drug resistance and immune-driven variations in hepatitis C virus (HCV) NS3/4A, NS5A and NS5B regions reveals a new approach toward personalized medicine.

    Science.gov (United States)

    Ikram, Aqsa; Obaid, Ayesha; Awan, Faryal Mehwish; Hanif, Rumeza; Naz, Anam; Paracha, Rehan Zafar; Ali, Amjad; Janjua, Hussnain Ahmed

    2017-01-01

    Cellular immune responses (T cell responses) during hepatitis C virus (HCV) infection are significant factors for determining the outcome of infection. HCV adapts to host immune responses by inducing mutations in its genome at specific sites that are important for HLA processing/presentation. Moreover, HCV also adapts to resist potential drugs that are used to restrict its replication, such as direct-acting antivirals (DAAs). Although DAAs have significantly reduced disease burden, resistance to these drugs is still a challenge for the treatment of HCV infection. Recently, drug resistance mutations (DRMs) observed in HCV proteins (NS3/4A, NS5A and NS5B) have heightened concern that the emergence of drug resistance may compromise the effectiveness of DAAs. Therefore, the NS3/4A, NS5A and NS5B drug resistance variations were investigated in this study, and their prevalence was examined in a large number of protein sequences from all HCV genotypes. Furthermore, potential CD4 + and CD8 + T cell epitopes were predicted and their overlap with genetic variations was explored. The findings revealed that many reported DRMs within NS3/4A, NS5A and NS5B are not drug-induced; rather, they are already present in HCV strains, as they were also detected in HCV-naïve patients. This study highlights several hot spots in which HLA and drug selective pressure overlap. Interestingly, these overlapping mutations were frequently observed among many HCV genotypes. This study implicates that knowledge of the host HLA type and HCV subtype/genotype can provide important information in defining personalized therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Anti-HCV activity of the Chinese medicinal fungus Cordyceps militaris.

    Science.gov (United States)

    Ueda, Youki; Mori, Kyoko; Satoh, Shinya; Dansako, Hiromichi; Ikeda, Masanori; Kato, Nobuyuki

    2014-05-02

    Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. Although the sustained virologic response rate in the treatment of genotype 1 using new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir) has been improved by more than 70%, several severe side effects such as skin rash/ageusia and advanced anemia have become a problem. Under these circumstances, a new type of anti-HCV oral drug with few side effects is needed. Our recently developed HCV drug assay systems, including the HuH-7 cell line-derived OR6 and AH1R, and the Li23 cell line-derived ORL8 and ORL11, allow genome-length HCV RNAs (several strains of genotype 1b) encoding renilla luciferase to replicate efficiently. Using these systems as anti-HCV candidates, we have identified numerous existing medicines that can be used against HCV with few side effects, such as statins and teprenon. To obtain additional anti-HCV candidates, we evaluated a number of oral health supplements, and found that the capsule but not the liquid form of Cordyceps militaris (CM) (Ascomycotinanorth, North Chinese caterpillar fungus), which is used as a Chinese herbal medicine, exhibited moderate anti-HCV activity. In combination with interferon-α or ribavirin, CM exhibited an additive inhibitory effect. Among the main components of CM, cordycepin, but not ergosterol, contributed to the anti-HCV activity of CM. In consideration of all these results, we suggest that CM would be useful as an oral anti-HCV agent in combination with interferon-α and/or ribavirin. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. The Association between Female Genital Cutting and Spousal HCV Infection in Egypt

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    Chris R. Kenyon

    2014-01-01

    Full Text Available Objective. To identify the risk factors for HCV infection within married couples in Egypt. Methods. In 2008 Egypt conducted its first nationally representative survey of HCV prevalence. 11126 of the 12780 individuals aged 15–59 year who were sampled agreed to participate and provided information via a questionnaire about demographic and behavioural characteristics and blood for HCV antibody and RNA analysis. We assessed the risk factors for HCV infection in a subsample of 5182 married individuals via multivariate logistic regression. Results. Overall HCV antibody prevalence in the married couples was 18.2% (95% CI, 16.8–19.6. HCV antibody prevalence was higher in the husbands (23.7% than the wives (12.1%; P<0.001. Having a spouse who was infected with HCV was an independent risk factor for HCV infection with odds ratios of 2.1 (95% CI, 1.6–2.9 and 2.2 (95% CI, 1.6–3.1 for women and men, respectively. Husbands whose wives had experienced female genital cutting (FGC had a higher prevalence of HCV and this relationship was driven by a strong association in urban areas. Amongst the women there was no association between FGC and HCV overall but in urban areas only women who had experienced FGC were HCV infected. Conclusions. This study provides additional evidence of the importance of intrafamilial transmission of HCV in Egypt.

  11. Discrepancy between Hepatitis C Virus Genotypes and NS4-Based Serotypes: Association with Their Subgenomic Sequences

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    Nan Nwe Win

    2017-01-01

    Full Text Available Determination of hepatitis C virus (HCV genotypes plays an important role in the direct-acting agent era. Discrepancies between HCV genotyping and serotyping assays are occasionally observed. Eighteen samples with discrepant results between genotyping and serotyping methods were analyzed. HCV serotyping and genotyping were based on the HCV nonstructural 4 (NS4 region and 5′-untranslated region (5′-UTR, respectively. HCV core and NS4 regions were chosen to be sequenced and were compared with the genotyping and serotyping results. Deep sequencing was also performed for the corresponding HCV NS4 regions. Seventeen out of 18 discrepant samples could be sequenced by the Sanger method. Both HCV core and NS4 sequences were concordant with that of genotyping in the 5′-UTR in all 17 samples. In cloning analysis of the HCV NS4 region, there were several amino acid variations, but each sequence was much closer to the peptide with the same genotype. Deep sequencing revealed that minor clones with different subgenotypes existed in two of the 17 samples. Genotyping by genome amplification showed high consistency, while several false reactions were detected by serotyping. The deep sequencing method also provides accurate genotyping results and may be useful for analyzing discrepant cases. HCV genotyping should be correctly determined before antiviral treatment.

  12. HCV knowledge among a sample of HCV positive Aboriginal Australians residing in New South Wales.

    Science.gov (United States)

    Wilson, Hannah; Brener, Loren; Jackson, L Clair; Saunders, Veronica; Johnson, Priscilla; Treloar, Carla

    2017-06-01

    Australian Aboriginal and Torres Strait Islanders are overrepresented in both the prevalence and incidence of the hepatitis C (HCV). HCV knowledge has been associated with a range of positive health behaviours. HCV knowledge has previously been investigated as a single construct; however examining different knowledge domains (i.e. transmission, risk of complications, testing and treatment) separately may be beneficial. This study investigated whether having greater HCV knowledge in different domains is associated with self-reported positive health behaviours. 203 Aboriginal people living with HCV completed a survey assessing HCV knowledge, testing and care, lifestyle changes since diagnosis and treatment intent. Respondents' knowledge was relatively high. Greater knowledge of risk of health complications was associated with undertaking more positive lifestyle changes since diagnosis. Respondents testing and treatment knowledge was significantly associated with incarceration, lifestyle changes since diagnosis and future treatment intentions. This study illustrates the importance of ensuring that knowledge is high across different HCV domains to optimise a range of positive health behaviours of Aboriginal people living with HCV. Future health promotion campaigns targeted at Aboriginal people living with HCV could benefit from broadening their focus from prevention to other domains such as testing and treatment.

  13. HBV, HCV, and HIV infection prevalence among prison staff in the light of occupational risk factors

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    Maria Gańczak

    2017-08-01

    Full Text Available Background: Objectives of the study: to assess the occupational risk for blood-borne infections (BBIs among prison staff (number/ circumstances of blood exposures and preventive methods used, and to estimate the prevalence of hepatitis B virus (HBV, hepatitis C virus (HCV and human immunodeficiency virus (HIV. Material and Methods: The survey, which included serological testing with the use of 3-generation enzyme-linked immunosorbent assays (ELISA was completed on active staff at a correctional facility in Goleniów, Poland, between June–July 2015. Results: Response rate was 38%, 87 participants (aged 22–64 years, median: 34 years agreed to participate. There were 88.5% males, correctional officers comprised 87.4% of the participants. Having had ≥ 1 blood exposure during professional career was reported by 28.7% respondents, 8% – sustained it in the preceding year. For correctional officers the last blood exposure was caused by a hollow-bore needle/razor blade during cell or manual searches. This was not reported by 83.3%. Participation rate in an infection control training was 85.1%. Hepatitis B virus vaccination uptake was 83.9%. Compliance with glove use was 75.9%, with protective eyewear – 28.7%. Regular use of both was reported by 9.2% of participants. The lack of their availability was the most common reason (79.7% for non-compliance. Anti-HBc (hepatitis B core antigen total/anti-HCV/anti-HIV prevalence was 2.3%, 1.1%, and 0%, respectively. Conclusions: Prison staff are at risk for occupational exposures to blood. Reporting of such incidents is poor, as well as compliance with personal protective equipment use, which place them at risk for acquiring BBIs. Anti-HCV prevalence is similar to that observed in the general population, anti-HBc total prevalence is lower, possibly due to high vaccination uptake, however, poor response rate limits precise prevalence estimates. Med Pr 2017;68(4:507–516

  14. Comprehensive Screening for Naturally Occurring Hepatitis C Virus Resistance to Direct-Acting Antivirals in the NS3, NS5A, and NS5B Genes in Worldwide Isolates of Viral Genotypes 1 to 6.

    Science.gov (United States)

    Patiño-Galindo, Juan Ángel; Salvatierra, Karina; González-Candelas, Fernando; López-Labrador, F Xavier

    2016-04-01

    There is no comprehensive study available on the natural hepatitis C virus (HCV) polymorphism in sites associated with resistance including all viral genotypes which may present variable susceptibilities to particular direct-acting antivirals (DAAs). This study aimed to analyze the frequencies, genetic barriers, and evolutionary histories of naturally occurring resistance-associated variants (RAVs) in the six main HCV genotypes. A comprehensive analysis of up to 103 RAVs was performed in 2,901, 2,216, and 1,344 HCV isolates for the NS3, NS5A, and NS5B genes, respectively. We report significant intergenotypic differences in the frequencies of natural RAVs for these three HCV genes. In addition, we found a low genetic barrier for the generation of new RAVs, irrespective of the viral genotype. Furthermore, in 1,126 HCV genomes, including sequences spanning the three genes, haplotype analysis revealed a remarkably high frequency of viruses carrying more than one natural RAV to DAAs (53% of HCV-1a, 28.5% of HCV-1b, 67.1% of HCV-6, and 100% of genotype 2, 3, 4, and 5 haplotypes). With the exception of HCV-1a, the most prevalent haplotypes showed RAVs in at least two different viral genes. Finally, evolutionary analyses revealed that, while most natural RAVs appeared recently, others have been efficiently transmitted over time and cluster in well-supported clades. In summary, and despite the observed high efficacy of DAA-based regimens, we show that naturally occurring RAVs are common in all HCV genotypes and that there is an overall low genetic barrier for the selection of resistance mutations. There is a need for natural DAA resistance profiling specific for each HCV genotype. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  15. Promiscuous prediction and conservancy analysis of CTL binding epitopes of HCV 3a viral proteome from Punjab Pakistan: an In Silico Approach

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    Idrees Muhammad

    2011-02-01

    Full Text Available Abstract Background HCV is a positive sense RNA virus affecting approximately 180 million people world wide and about 10 million Pakistani populations. HCV genotype 3a is the major cause of infection in Pakistani population. One of the major problems of HCV infection especially in the developing countries that limits the limits the antiviral therapy is the long term treatment, high dosage and side effects. Studies of antigenic epitopes of viral sequences of a specific origin can provide an effective way to overcome the mutation rate and to determine the promiscuous binders to be used for epitope based subunit vaccine design. An in silico approach was applied for the analysis of entire HCV proteome of Pakistani origin, aimed to identify the viral epitopes and their conservancy in HCV genotypes 1, 2 and 3 of diverse origin. Results Immunoinformatic tools were applied for the predictive analysis of HCV 3a antigenic epitopes of Pakistani origin. All the predicted epitopes were then subjected for their conservancy analysis in HCV genotypes 1, 2 and 3 of diverse origin (worldwide. Using freely available web servers, 150 MHC II epitopes were predicted as promiscuous binders against 51 subjected alleles. E2 protein represented the 20% of all the predicted MHC II epitopes. 75.33% of the predicted MHC II epitopes were (77-100% conserve in genotype 3; 47.33% and 40.66% in genotype 1 and 2 respectively. 69 MHC I epitopes were predicted as promiscuous binders against 47 subjected alleles. NS4b represented 26% of all the MHC I predicted epitopes. Significantly higher epitope conservancy was represented by genotype 3 i.e. 78.26% and 21.05% for genotype 1 and 2. Conclusions The study revealed comprehensive catalogue of potential HCV derived CTL epitopes from viral proteome of Pakistan origin. A considerable number of predicted epitopes were found to be conserved in different HCV genotype. However, the number of conserved epitopes in HCV genotype 3 was

  16. Epidemiological manifestations of hepatitis C virus genotypes and its association with potential risk factors among Libyan patients

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    Daw Mohamed A

    2010-11-01

    Full Text Available Abstract Background The information on hepatitis C virus genotypes and subtypes among Libyan population and its association with various risk factors is not known. The objectives of this study were to determine the epidemiological manifestations of HCV genotypes among Libyan patients and their association with certain potential risk factors. Methods A total of 1240 of HCV infected patients registered at Tripoli Medical Centre were studied in five years period from January 2005 to October 2009. The information were reviewed and the data were collected. A sample from each patient (785 male; 455 female was analysed for genotyping and sub-typing using specific genotyping assay. The information was correlated with the risk factors studied and the statistical data were analyzed using SPSS version 11.5. Results Off the total patients studied, four different genotypes were reported, including genotypes 1, 2, 3, and 4. Genotype4 was the commonest (35.7%, followed by genotype1 (32.6%. According to subtypes 28% were unclassified genotype 4, 14.6% were genotype 1b and some patients infected with more than one subtype (2.3% genotype 4c/d, 1% genotype 2a/c. Genotypes 1 was the commonest among males, while genotype 4 among females. According to the risk factors studied, Genotype1 and genotype 4 were found with most of the risk factors. Though they were particularly evident surgical intervention, dental procedures and blood transfusion while genotype 1 was only followed by genotype 3 mainly which mainly associated with certain risk groups such as intravenous drug abusers. Conclusion Here in we report on a detailed description of HCV genotype among Libyans. The most common genotype was type 4 followed by genotype 1, other genotypes were also reported at a low rate. The distribution of such genotypes were also variable according to gender and age. The commonly prevalent genotypes found to be attributable to the medical -related transmission of HCV, such as blood

  17. Role of IL-28B polymorphisms in virologic response to combined pegylated interferon and ribavirin therapy in genotype 4 chronic HCV infected patients with and without cirrhosis

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    Amira Youssef Shaala

    2015-09-01

    Conclusion: In Egypt, where chronic HCV genotype 4 and schistosoma coinfection predominate, both schistosoma infection and cirrhosis are more potent than IL28B polymorphisms as strong baseline negative predictors of hepatitis C treatment response.

  18. Clinical characteristics, healthcare costs, and resource utilization in hepatitis C vary by genotype.

    Science.gov (United States)

    Goolsby Hunter, Alyssa; Rosenblatt, Lisa; Patel, Chad; Blauer-Peterson, Cori; Anduze-Faris, Beatrice

    2017-05-01

    In the United States, approximately 3 million people are infected with hepatitis C virus (HCV). Genotypes of HCV variably affect disease progression and treatment response. However, the relationships between HCV genotypes and liver disease progression, healthcare resource utilization, and healthcare costs have not been fully explored. In this retrospective study of patients with chronic hepatitis C (CHC), healthcare claims from a large US health plan were used to collect data on patient demographic and clinical characteristics. Main outcome measures include healthcare resource utilization (HCRU) and healthcare costs. Linked laboratory data provided genotype and select measures to determine liver disease severity. The sample (mean age 50.6 years, 63.5% male) included 10,331 patients, of whom 79.1% had genotype (GT)1, 12.8% had GT2, and 8.1% had GT3. Descriptive analyses demonstrated variation by HCV genotype in liver and non-liver related comorbidities, liver disease severity, and healthcare costs. The highest percentage of patients with liver-related comorbidities and advanced liver disease was found among those with GT3. Meanwhile, patients with GT2 had lower HCRU and the lowest costs, and patients with GT1 had the highest total all-cause costs. These differences may reflect differing rates of non-liver-related comorbidities and all-cause care. Multivariable analyses showed that genotype was a significant predictor of costs and liver disease severity: compared with patients having GT1, those with GT3 were significantly more likely to have advanced liver disease. Patients with GT2 were significantly less likely to have advanced disease and more likely to have lower all-cause costs. Results may not be generalizable to patients outside the represented commercial insurance plans, and analysis of a prevalent population may underestimate HCRU and costs relative to a sample of treated patients. These results suggest that liver disease progression varies by genotype and

  19. Analysis of resistance-associated substitutions in acute hepatitis C virus infection by deep sequencing across six genotypes and three continents.

    Science.gov (United States)

    Eltahla, A A; Rodrigo, C; Betz-Stablein, B; Grebely, J; Applegate, T; Luciani, F; Schinkel, J; Dore, G J; Page, K; Bruneau, J; Morris, M D; Cox, A L; Kim, A Y; Shoukry, N H; Lauer, G M; Maher, L; Hellard, M; Prins, M; Lloyd, A R; Bull, R A

    2017-01-01

    Several direct-acting antivirals (DAAs) have been approved for the treatment of chronic hepatitis C virus (HCV) infections, opening the door to highly effective interferon-free treatment regimens. Resistance-associated substitutions (RASs) have been reported both in treatment-naïve patients and following treatment with protease (NS3), phosphoprotein (NS5A) and polymerase (NS5B) inhibitors. The prevalence of naturally occurring RASs in untreated HCV-infected individuals has mostly been analysed in those infected with genotype 1 (GT1), in the late phase of infection, and only within limited regions of the genome. Furthermore, the geographic distribution of RASs remains poorly characterized. In this study, we used next-generation sequencing to analyse full-length HCV genomes for the prevalence of RASs in acute HCV infections identified in nine international prospective cohorts. RASs were analysed in 179 participants infected with all six major HCV genotypes (GT1-GT6), and the geographic distribution of RASs was assessed in 107 GT1a and GT3a samples. While RASs were detected at varied frequencies across the three genomic regions, and between genotypes, RASs relevant to multiple DAAs in the leading IFN-free regimens were rarely detected in combination. Low-frequency RASs (<10% of the viral population) were also shown to have a GT-specific distribution. The main RASs with geographic associations were NS3 Q80K in GT1a samples and NS5B N142T in GT3a. These data provide the backdrop for prospective surveillance of RASs during DAA treatment scale-up. © 2016 John Wiley & Sons Ltd.

  20. Demographic and anthropometrical analysis and genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil

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    R. Focaccia

    Full Text Available Hepatitis C virus (HCV infection is a serious public health problem, since 80% to 85% of HCV carriers develop a persistent infection that can progress into liver cirrhosis and hepatocarcinoma. Considering that the response of hepatitis C patients to combination therapy with interferon and ribavirin depends on HCV characteristics as well as on host features, we made a retrospective analysis of demographic and anthropometrical data and HCV genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil. The medical records of 4,996 patients were reviewed, 81% from public and 19% from private institutions. Patients' median age was 46 years, and there was a higher prevalence of male (62% and white patients (80%. The analysis of HCV-infecting strains showed a predominance of genotype 1 (64% over genotypes 2 and 3. The patients' mean weight was 70.6 kg, and 65% of the patients weighed less than 77kg. Overweight and obesity were observed in 37.8% and 13.6% of the patients, respectively. Since a body weight of 75 kg or less has been considered an independent factor that significantly increases the odds of achieving a sustained virological response, the Brazilian population seems to have a more favorable body weight profile to achieve a sustained response than the American and European populations. The finding that 65% of chronic hepatitis C patients have a body weight of 77 kg or less may have a positive pharmacoeconomic impact on the treatment of genotype 1 HCV patients with weight-based doses of peginterferon.

  1. HBV-DNA in hemodialysis patients infected by HCV

    International Nuclear Information System (INIS)

    Arababadi, Mohammad Kazemi; Hassanshahi, Gholamhossein; Yousefi, Hassan

    2009-01-01

    End-stage renal disease patients on chronic hemodialysis (HD) patients are at risk for both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, and they may coexist. To determine the prevalence and clinical impact of HBV and HCV infection, we studied poly chain reaction (PCR) and reverse transcription (RT)-PCR on the blood samples of 90 HD patients in Kerman, Iran. ELISA test was used to detect anti-HBc, anti-HBs and HBs Ag. We found that 30 out of 90 (33.3%) patients were PCR-RT-PCR positive for HCV-RNA. No HBV-DNA (0%) was detected through the PCR study in both positive and negative HCV-RNA patient groups. Though none of the samples was HBsAg positive, 10 (33.3%) HCV-RNA positive patients were anti-HBc positive, and 12 (40.7%) were anti-HBs positive. We conclude that prevalence of hepatitis C infection is high in HD patients in our region, but not associated with active HBV infection. (author)

  2. Daclatasvir plus peginterferon and ribavirin is noninferior to peginterferon and ribavirin alone, and reduces the duration of treatment for HCV genotype 2 or 3 infection

    DEFF Research Database (Denmark)

    Dore, Gregory J; Lawitz, Eric; Hézode, Christophe

    2015-01-01

    BACKGROUND & AIMS: Twenty-four weeks of treatment with peginterferon and ribavirin for chronic hepatitis C virus (HCV) genotype 2 or 3 infection produces a sustained virologic response (SVR) in 70%-80% of patients. We performed a randomized, double-blind, phase 2b study to assess whether adding d...

  3. [The velocity of HCV subtype 6a transmission in southwest China].

    Science.gov (United States)

    Hong, Guo-hu; Tan, Zhao-xia; Guo, Yan; Mao, Qing

    2011-07-01

    To estimate the velocity of HCV subtype 6a transmission in Southwest China. The HCV CE1 region from 61 patients infected with HCV genotype 6 were amplificated by RT-PCR and sequenced. The subtypes were identified, and the period of HCV 6a strains originated in southwest china was estimated by using molecular clock phylogenetic analysis. The velocity of HCV subtype 6a transmission in southwest China was estimated by BEAST v1.6.1 and Tracer v1.5 software theoretically. Most of HCV 6a strains distributed in Southwest China origine around the year 1968 and at last 4 epidemic strains existed. The earlier origine strains could be isolated both in intravenous drug users (IDU) and non-IDU patients. After 1997, the HCV 6a strains transmission in southwest China accelerated and the trend intensified in 2007. HCV 6a strains spread fastly both in IDU and non-IDU patients, which might be the main HCV subtype distributed in Southwest China in the future.

  4. TRAIL receptor I (DR4) polymorphisms C626G and A683C are associated with an increased risk for hepatocellular carcinoma (HCC) in HCV-infected patients

    International Nuclear Information System (INIS)

    Körner, Christian; Nattermann, Jacob; Spengler, Ulrich; Nischalke, Hans Dieter; Riesner, Katarina; Krämer, Benjamin; Eisenhardt, Marianne; Glässner, Andreas; Wolter, Franziska; Berg, Thomas; Müller, Tobias; Sauerbruch, Tilman

    2012-01-01

    Tumour surveillance via induction of TRAIL-mediated apoptosis is a key mechanism, how the immune system prevents malignancy. To determine if gene variants in the TRAIL receptor I (DR4) gene affect the risk of hepatitis C virus (HCV)-induced liver cancer (HCC), we analysed DR4 mutations C626G (rs20575) and A683C (rs20576) in HCV-infected patients with and without HCC. Frequencies of DR4 gene polymorphisms were determined by LightSNiP assays in 159 and 234 HCV-infected patients with HCC and without HCC, respectively. 359 healthy controls served as reference population. Distribution of C626G and A683C genotypes were not significantly different between healthy controls and HCV-positive patients without HCC. DR4 variants 626C and 683A occurred at increased frequencies in patients with HCC. The risk of HCC was linked to carriage of the 626C allele and the homozygous 683AA genotype, and the simultaneous presence of the two risk variants was confirmed as independent HCC risk factor by Cox regression analysis (Odds ratio 1.975, 95% CI 1.205-3.236; p = 0.007). Furthermore HCV viral loads were significantly increased in patients who simultaneously carried both genetic risk factors (2.69 ± 0.36 × 10 6 IU/ml vs. 1.81 ± 0.23 × 10 6 IU/ml, p = 0.049). The increased prevalence of patients with a 626C allele and the homozygous 683AA genotype in HCV-infected patients with HCC suggests that these genetic variants are a risk factor for HCC in chronic hepatitis C

  5. Modelling the impact of incarceration and prison-based hepatitis C virus (HCV) treatment on HCV transmission among people who inject drugs in Scotland.

    Science.gov (United States)

    Stone, Jack; Martin, Natasha K; Hickman, Matthew; Hutchinson, Sharon J; Aspinall, Esther; Taylor, Avril; Munro, Alison; Dunleavy, Karen; Peters, Erica; Bramley, Peter; Hayes, Peter C; Goldberg, David J; Vickerman, Peter

    2017-07-01

    People who inject drugs (PWID) experience high incarceration rates, and previous incarceration is associated with elevated hepatitis C virus (HCV) transmission risk. In Scotland, national survey data indicate lower HCV incidence in prison than the community (4.3 versus 7.3 per 100 person-years), but a 2.3-fold elevated transmission risk among recently released (prison-related prevention interventions, including scaling-up direct-acting antivirals (DAAs) in prison. Dynamic mathematical modelling of incarceration and HCV transmission, using approximate Bayesian computation for model calibration. Scotland, UK. A simulated population of PWID. Population-attributable fraction (PAF) of incarceration to HCV transmission among PWID. Decrease in HCV incidence and chronic prevalence due to current levels of prison opiate substitution therapy (OST; 57% coverage) and HCV treatment, as well as scaling-up DAAs in prison and/or preventing the elevated risk associated with prison release. Incarceration contributes 27.7% [PAF; 95% credible interval (CrI) -3.1 to 51.1%] of HCV transmission among PWID in Scotland. During the next 15 years, current HCV treatment rates (10.4/6.8 per 1000 incarcerated/community PWID annually), with existing prison OST, could reduce incidence and chronic prevalence among all PWID by a relative 10.7% (95% CrI = 8.4-13.3%) and 9.7% (95% CrI = 7.7-12.1%), respectively. Conversely, without prison OST, HCV incidence and chronic prevalence would decrease by 3.1% (95% CrI = -28.5 to 18.0%) and 4.7% (95% CrI = -11.3 to 14.5%). Additionally, preventing the heightened risk among recently released PWID could reduce incidence and chronic prevalence by 45.0% (95% CrI = 19.7-57.5%) and 33.3% (95% CrI = 15.6-43.6%) or scaling-up prison HCV treatments to 80% of chronic PWID prison entrants with sufficient sentences (>16 weeks) could reduce incidence and prevalence by 45.6% (95% CrI = 38.0-51.3%) and 45.5% (95% CrI = 39.3-51.0%), respectively

  6. Geographic distribution of hepatitis C virus genotype 6 subtypes in Thailand.

    Science.gov (United States)

    Akkarathamrongsin, Srunthron; Praianantathavorn, Kesmanee; Hacharoen, Nisachol; Theamboonlers, Apiradee; Tangkijvanich, Pisit; Tanaka, Yasuhito; Mizokami, Masashi; Poovorawan, Yong

    2010-02-01

    The nucleotide sequence of hepatitis C virus (HCV) genotype 6 found mostly in south China and south-east Asia, displays profound genetic diversity. The aim of this study to determine the genetic variability of HCV genotype 6 (HCV-6) in Thailand and locate the subtype distribution of genotype 6 in various geographic areas. Four hundred nineteen anti-HCV positive serum samples were collected from patients residing in - the central part of the country. HCV RNA positive samples based on reverse transcriptase- polymerase chain reaction (RT-PCR) of the 5'UTR were amplified with primers specific for the core and NS5B regions. Nucleotide sequences of both regions were analyzed for the genotype by phylogenetic analysis. To determine geographic distribution of HCV-6 subtypes, a search of the international database on subtype distribution in the respective countries was conducted. Among 375 HCV RNA positive samples, 71 had HCV-6 based on phylogenetic analysis of partial core and NS5B regions. The subtype distribution in order of predominance was 6f (56%), 6n (22%), 6i (11%), 6j (10%), and 6e (1%). Among the 13 countries with different subtypes of HCV-6, most sequences have been reported from Vietnam. Subtype 6f was found exclusively in Thailand where five distinct HCV-6 subtypes are circulating. HCV-6, which is endemic in south China and south-east Asia, displays profound genetic diversity and may have evolved over a considerable period of time. (c) 2009 Wiley-Liss, Inc.

  7. Detection and genotyping of torque teno virus (TTV) in healthy blood donors and patients infected with HBV or HCV in Qatar.

    Science.gov (United States)

    AbuOdeh, Raed; Al-Mawlawi, Naema; Al-Qahtani, Ahmed A; Bohol, Marie Fe F; Al-Ahdal, Mohammed N; Hasan, Haydar A; AbuOdeh, Lamees; Nasrallah, Gheyath K

    2015-07-01

    Torque Teno virus (TTV) has been associated with non A-G hepatitis. The goal of this study was to estimate the infection rates and genotypic characteristics of TTV in the State of Qatar. A total of 644 blood samples representing different nationalities: (i) Qatari (118) and (ii) non-Qatari (526) nationals (mostly from Arab and South Eeast Asia countries) were tested for the presence of TTV DNA by nested PCR. The majority (573) of the blood samples belonged to healthy blood donors, whereas 54 and 53 of the blood samples belonged to patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV), respectively. The results obtained showed that the TTV infection rates in the healthy blood donors, and those infected with HBV or HCV patients were 81.4, 90.75 and 84.9%, respectively. Significant association between TTV viremia and age, or nationality was observed. Sequence analysis of PCR fragments amplified from the 5'-untranslated region (5'-UTR) of all (531) TTV positive samples showed that 65.5% (348/531) of the PCR fragment sequences were classified into main genogroup 3, followed by main genogroups 5 (24%), 2 (5.8%), and 1 (4.7%). Genogroup 4 was not detected among the our studied subjects. Phylogenetic and pairwise analyses using sequences from TTV viremic samples also showed an overall close similarity to the main genogroup 3. In conclusion, there was no significant difference in the rates of TTV detection among Qataris and non-Qataris and several genotypes, mainly genotype 3, were isolated. © 2015 Wiley Periodicals, Inc.

  8. Prevalence of pre-treatment hepatitis C virus NS5A resistance associated amino-acid substitutions in genotype 1A infected patients in Scotland.

    Science.gov (United States)

    Bradley-Stewart, Amanda; Goldstein, Emily; MacLean, Alasdair; Gunson, Rory

    2018-04-01

    Hepatitis C (HCV) NS5A resistance associated amino-acid substitutions (RAS) can exist at baseline in treatment naïve individuals and have been shown to be associated with lower rates of sustained virological response (SVR) for patients infected with HCV genotype 1A (G1A) following treatment with NS5A inhibitors. The aim of this study was to measure the prevalence of baseline NS5A resistance in Scotland. The study population consisted of 531 treatment naïve, G1A infected patients. The patient samples were collected between March and September 2017. The NS5A region was amplified and sequenced. Baseline NS5A resistance in Scotland is high (16.8%) and is comparable to rates reported by a number of previously published studies. The high rate of baseline RAS, together with the high cost of direct-acting antivirals (DAAs), supports resistance testing to guide current patient treatment. However, given the rate at which new DAAs are currently being licensed with ever broader genotype efficacy and higher SVR rates, baseline resistance testing may not be required in the near future. Baseline NS5A inhibitor resistance is high. The results of the present study support performing resistance testing at baseline for current regimens. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  9. Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections

    DEFF Research Database (Denmark)

    Dalgard, Olav; Weiland, Ola; Noraberg, Geir

    2017-01-01

    BACKGROUND AND AIMS: Chronic hepatitis C virus (HCV) genotype 3 infection with advanced liver disease has emerged as the most challenging to treat. We retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes for treatment of HCV genotype 3 infections in a real life setting...... in Scandinavia. METHODS: Consecutive patients with chronic HCV genotype 3 infection were enrolled at 16 treatment centers in Denmark, Sweden, Norway and Finland. Patients who had received a SOF containing regimen were included. The fibrosis stage was evaluated by liver biopsy or transient liver elastography...... was similar for all treatment regimens, but lower in men (p = 0.042), and in patients with decompensated liver disease (p = 0.004). CONCLUSION: We found that sofosbuvir based treatment in a real-life setting could offer SVR rates exceeding 90% in patients with HCV genotype 3 infection and advanced liver...

  10. Association of HCV with diabetes mellitus: an Egyptian case-control study

    Directory of Open Access Journals (Sweden)

    Esmat Gamal G

    2011-07-01

    Full Text Available Abstract Background The highest Hepatitis C Virus (HCV prevalence in the world occurs in Egypt. Several studies from different parts of the world have found that 13% to 33% of patients with chronic HCV have associated diabetes, mostly type II Diabetes Mellitus (DM. In Egypt the prevalence of DM is 25.4% among HCV patients. Therefore, it is important to identify the magnitude of the problem of diabetes in order to optimize the treatment of chronic hepatitis C. Methods The objective of this case-control study was to evaluate the prevalence of DM and other extrahepatic (EH manifestations among patients with different HCV morbidity stages including asymptomatic, chronic hepatic and cirrhotic patients. In this study, 289 HCV patients older than 18 were selected as cases. Also, 289 healthy controls were included. Laboratory investigations including Liver Function tests (LFT and blood glucose level were done. Also serological assays including cryoglobulin profile, rheumatoid factor, antinuclear antibody, HCV-PCR were performed. Results Out of 289 HCV cases, 40 (13.84% were diabetic. Out of 289 healthy controls, 12 (4.15% were diabetic. It was found that the diabetic HCV group mean age was [48.1 (± 9.2]. Males and urbanians represented 72.5% and 85% respectively. Lower level of education was manifested in 52.5% and 87.5% were married. In the nondiabetic HCV group mean age was [40.7 (± 10.4]. Males and urbanians represented 71.5% and 655% respectively. secondary and higher level of education was attained in 55.4% and 76.7% were married. Comparing between the diabetic HCV group and the non diabetic HCV group, age, residence and alcohol drinking were the only significant factors affecting the incidence of diabetes between the two groups. There was no significant difference regarding sonar findings although cirrhosis was more prevalent among diabetic HCV cases and the fibrosis score was higher in diabetic HCV patients than among the non diabetic HCV cases

  11. Circulating sCD14 is associated with virological response to pegylated-interferon-alpha/ribavirin treatment in HIV/HCV co-infected patients.

    Directory of Open Access Journals (Sweden)

    Giulia Marchetti

    Full Text Available Microbial translocation (MT through the gut accounts for immune activation and CD4+ loss in HIV and may influence HCV disease progression in HIV/HCV co-infection. We asked whether increased MT and immune activation may hamper anti-HCV response in HIV/HCV patients.98 HIV/HCV patients who received pegylated-alpha-interferon (peg-INF-alpha/ribavirin were retrospectively analyzed. Baseline MT (lipopolysaccharide, LPS, host response to MT (sCD14, CD38+HLA-DR+CD4+/CD8+, HCV genotype, severity of liver disease were assessed according to Early Virological Response (EVR: HCV-RNA <50 IU/mL at week 12 of therapy or ≥2 log(10 reduction from baseline after 12 weeks of therapy and Sustained Virological Response (SVR: HCV-RNA <50 IU/mL 24 weeks after end of therapy. Mann-Whitney/Chi-square test and Pearson's correlation were used. Multivariable regression was performed to determine factors associated with EVR/SVR.71 patients displayed EVR; 41 SVR. Patients with HCV genotypes 1-4 and cirrhosis presented a trend to higher sCD14, compared to patients with genotypes 2-3 (p = 0.053 and no cirrhosis (p = 0.052. EVR and SVR patients showed lower levels of circulating sCD14 (p = 0.0001, p = 0.026, respectively, but similar T-cell activation compared to Non-EVR (Null Responders, NR and Non-SVR (N-SVR subjects. sCD14 resulted the main predictive factor of EVR (0.145 for each sCD14 unit more, 95%CI 0.031-0.688, p = 0.015. SVR was associated only with HCV genotypes 2-3 (AOR 0.022 for genotypes 1-4 vs 2-3, 95%CI 0.001-0.469, p = 0.014.In HIV/HCV patients sCD14 correlates with the severity of liver disease and predicts early response to peg-INF-alpha/ribavirin, suggesting MT-driven immune activation as pathway of HIV/HCV co-infection and response to therapy.

  12. Advances in the treatment of HIV/HCV coinfection in adults.

    Science.gov (United States)

    Schlabe, Stefan; Rockstroh, Jürgen K

    2018-01-01

    Direct-acting antivirals (DAA) have revolutionized the modern treatment of chronic hepatitis C (HCV). These highly efficacious, well-tolerated, all-oral HCV regimens allow cure of HCV in over 95% of HCV-monoinfected as well as HIV/HCV-coinfected patients with short treatment durations of 8-12 weeks. Areas covered: This review will address recent developments of DAA-therapy in HIV/HCV-coinfected patients in clinical trials and real life cohorts and evaluate remaining challenges, particularly resistance, drug-drug interactions, acute HCV infection and liver transplantation focusing on HIV/HCV-coinfected patients. Expert opinion: Indeed, all available data have shown that HIV/HCV-coinfection has no impact on HCV-treatment outcome. Management, indication of therapy and follow-up of HCV-infection are now the same for both patient populations. HIV/HCV-coinfected patients however, require careful evaluation of potential drug-drug-interactions between HCV drugs and HIV antiretroviral therapy, medication for substance abuse and other comedications. The few remaining gaps in DAA-therapy in particular treatment of cirrhotic treatment-experienced genotype 3 infections, decompensated cirrhosis, chronic kidney disease and patients with prior DAA treatment failure have mostly been overcome by the development of new HCV agents recently licensed. Clearly, the biggest challenge globally remains the access to treatment and the inclusion of all patient populations affected in particular people who inject drugs (PWID).

  13. Recurrence of hepatitis C virus genotype- 4 infection following orthotopic liver transplantation: natural history and predictors of outcome

    International Nuclear Information System (INIS)

    Mudawi, Hatim; Helmy, Ahmed; Kamel, Yasser; AlSaghier, Mohammed; AlSofayan, Mohammed; AlSebayel, Mohammed; Khalaf, Hatem; AlBahili, Hamad; Alhiek, Yasser; Alawi, Khalil; Mohamed, Hazem; AlJedai, Ahmed; AlHamoudi, Waleed; Abdo, Ayman

    2007-01-01

    There are few reports on hepatitis C virus genotype 4 (HCV-4) recurrences after orthotopic liver transplantation (OLT). Therefore, we undertook a study to determine the epidemiological, clinical and virological characteristics of patients with biopsy-proven recurrent HCV infection and analyzed the factors that influence recurrent disease severity. We also compared disease recurrence and outcomes between HCV-4 and other genotypes. All patients who underwent OLT (locally or abroad) for HCV related hepatic cirrhosis from 1991 to 2006 and had recurrent HCV infection were identified. Clinical, laboratory and pathological data before and after OLT were collected and analyzed. Of 116 patients who underwent OLT for hepatitis C, 46 (39.7%) patients satisfied the criteria of recurrent hepatitis C. Twenty-nine (63%) patients were infected with HCV genotype 4. Mean (SD) for age was 54.9 (10.9) years. Nineteen of the HCV genotype 4 patients (65.5%) were males, 21 (72.4%) received deceased donor grafts, and 7 (24.1%) developed > - 1 acute rejection episodes. Pathologically, 7 (24.1%) and 4 (13.8%) patients had inflammation grade 3-4 and fibrosis stage 3-4, respectively. Follow-up biopsy in 9 (31%) HCV genotype 4 patients showed stable, worse and improved fibrosis stage in 5, 2 and 2 patients, respectively. Of the 7 patients in the recurrent HCV group who died, 6 were infected with genotype 4 and 4 of them died of HCV-related disease. This analysis suggests that HCV recurrence following OLT in HCV-4 patients is not significantly different from its recurrence for other genotypes. (author)

  14. Genotyping of Hepatitis C virus isolated from hepatitis patients in Southeast of Iran by taqman realtime PCR

    International Nuclear Information System (INIS)

    Farivar, T.N.; Johari, P.

    2011-01-01

    Objectives: To check TaqMan Realtime PCR in detecting genotypes of hepatitis C virus in Iran. Methods: From July 2007 to April 2009, HCV genotyping was done on 52 patients who were referred to Research Centre for infectious Disease and Tropical Medicine, in Bou-Ali Hospital, Zahedan University of Medical Sciences. All these patients had proven hepatitis C infection. Results: Out of 52 anti HCV positive samples, 28(53.84%) had genotype 1, 2 cases (3.88 %) had genotype 2 , 12 (23.08 %) had genotype 3 and 7 (13.4 %) had genotype 4 . Mixed infection with genotypes 1 and 3 was seen in 3 cases (5.77 %). Conclusion: TaqMan probes for detecting genotyping of HCV were successful in picking genotyping of HCV infection especially those with mixed genotypes. (author)

  15. Insulin resistance and liver steatosis in chronic hepatitis C infection genotype 3.

    Science.gov (United States)

    Abenavoli, Ludovico; Masarone, Mario; Peta, Valentina; Milic, Natasa; Kobyliak, Nazarii; Rouabhia, Samir; Persico, Marcello

    2014-11-07

    Hepatitis C virus (HCV) infection is a common chronic liver disease worldwide. Non-alcoholic fatty liver disease and insulin resistance (IR) are the major determinants of fibrosis progression and response to antiviral therapy. The pathogenetic link between IR and chronic HCV infection is complex, and is associated with HCV genotype. Liver steatosis is the most common in the patients infected with genotype 3 virus, possibly due to direct effects of genotype 3 viral proteins. To the contrary, hepatic steatosis in the patients infected with other genotypes is thought to be mostly due to the changes in host metabolism, involving IR. In HCV genotype 3, liver steatosis correlates with viral load, reverts after reaching the sustained virologic response and reoccurs in the relapsers. A therapeutic strategy to improve IR and liver steatosis and subsequently the response to antiviral treatment in these patients is warranted.

  16. Introduction and Utilization of High Priced HCV Medicines across Europe; Implications for the Future

    Science.gov (United States)

    de Bruijn, Winnie; Ibáñez, Cristina; Frisk, Pia; Bak Pedersen, Hanne; Alkan, Ali; Vella Bonanno, Patricia; Brkičić, Ljiljana S.; Bucsics, Anna; Dedet, Guillaume; Eriksen, Jaran; Fadare, Joseph O.; Fürst, Jurij; Gallego, Gisselle; Godói, Isabella P.; Guerra Júnior, Augusto A.; Gürsöz, Hakkı; Jan, Saira; Jones, Jan; Joppi, Roberta; Kerman, Saim; Laius, Ott; Madzikwa, Newman; Magnússon, Einar; Maticic, Mojca; Markovic-Pekovic, Vanda; Massele, Amos; Ogunleye, Olayinka; O'Leary, Aisling; Piessnegger, Jutta; Sermet, Catherine; Simoens, Steven; Tiroyakgosi, Celda; Truter, Ilse; Thyberg, Magnus; Tomekova, Kristina; Wladysiuk, Magdalena; Vandoros, Sotiris; Vural, Elif H.; Zara, Corinne; Godman, Brian

    2016-01-01

    Background: Infection with the Hepatitis C Virus (HCV) is a widespread transmittable disease with a diagnosed prevalence of 2.0%. Fortunately, it is now curable in most patients. Sales of medicines to treat HCV infection grew 2.7% per year between 2004 and 2011, enhanced by the launch of the protease inhibitors (PIs) boceprevir (BCV) and telaprevir (TVR) in addition to ribavirin and pegylated interferon (pegIFN). Costs will continue to rise with new treatments including sofosbuvir, which now include interferon free regimens. Objective: Assess the uptake of BCV and TVR across Europe from a health authority perspective to offer future guidance on dealing with new high cost medicines. Methods: Cross-sectional descriptive study of medicines to treat HCV (pegIFN, ribavirin, BCV and TVR) among European countries from 2008 to 2013. Utilization measured in defined daily doses (DDDs)/1000 patients/quarter (DIQs) and expenditure in Euros/DDD. Health authority activities to influence treatments categorized using the 4E methodology (Education, Engineering, Economics and Enforcement). Results: Similar uptake of BCV and TVR among European countries and regions, ranging from 0.5 DIQ in Denmark, Netherlands and Slovenia to 1.5 DIQ in Tayside and Catalonia in 2013. However, different utilization of the new PIs vs. ribavirin indicates differences in dual vs. triple therapy, which is down to factors including physician preference and genotypes. Reimbursed prices for BCV and TVR were comparable across countries. Conclusion: There was reasonable consistency in the utilization of BCV and TVR among European countries in comparison with other high priced medicines. This may reflect the social demand to limit the transmission of HCV. However, the situation is changing with new curative medicines for HCV genotype 1 (GT1) with potentially an appreciable budget impact. These concerns have resulted in different prices across countries, with their impact on budgets and patient outcomes

  17. Introduction and utilisation of high priced HCV medicines across Europe; implications for the future

    Directory of Open Access Journals (Sweden)

    Winnie de Bruijn

    2016-07-01

    Full Text Available Background: Infection with the Hepatitis C Virus (HCV is a widespread transmittable disease with a diagnosed prevalence of 2.0%. Fortunately, it is now curable in most patients. Sales of medicines to treat HCV infection grew 2.7% per year between 2004 and 2011, enhanced by the launch of the protease inhibitors (PIs boceprevir (BCV and telaprevir (TVR in addition to ribavirin and pegylated interferon (pegIFN. Costs will continue to rise with new treatments including sofosbuvir, which now include interferon free regimens. Objective: Assess the uptake of BCV and TVR across Europe from a health authority perspective to offer future guidance on dealing with new high cost medicines. Methods: Cross-sectional descriptive study of medicines to treat HCV (pegIFN, ribavirin, BCV and TVR among European countries from 2008 to 2013. Utilisation measured in defined daily doses (DDDs/ 1000 patients/ quarter (DIQs and expenditure in Euros/ DDD. Health authority activities to influence treatments categorised using the 4E methodology (Education, Engineering, Economics and Enforcement. Results: Similar uptake of BCV and TVR among European countries and regions, ranging from 0.5 DIQ in Denmark, Netherlands and Slovenia to 1.5 DIQ in Tayside and Catalonia in 2013. However, different utilisation of the new PIs versus ribavirin indicates differences in dual versus triple therapy, which is down to factors including physician preference and genotypes. Reimbursed prices for BCV and TVR were comparable across countries. Conclusion: There was reasonable consistency in the utilisation of BCV and TVR among European countries in comparison with other high priced medicines. This may reflect the social demand to limit the transmission of HCV. However, the situation is changing with new curative medicines for HCV genotype 1 (GT1 with potentially an appreciable budget impact. These concerns have resulted in different prices negotiations across countries, with their impact

  18. Genotypes of HBV and HCV among HIV-1 co-infected individuals in ...

    African Journals Online (AJOL)

    Background: Hepatitis B and Hepatitis C viruses are the major causes of liver disease worldwide. Co-infections with HBV and HCV have turned out to be increasingly very common among people living with HIV, leading to a major public health concern. Objective: To determine HBV and HCV diversity among HIV infected ...

  19. Epidemiology of hepatitis C in Croatia in the European context.

    Science.gov (United States)

    Vilibic-Cavlek, Tatjana; Kucinar, Jasmina; Kaic, Bernard; Vilibic, Maja; Pandak, Nenad; Barbic, Ljubo; Stevanovic, Vladimir; Vranes, Jasmina

    2015-08-28

    We analyzed prevalence, risk factors and hepatitis C virus (HCV) genotype distribution in different population groups in Croatia in the context of HCV epidemiology in Europe, with the aim to gather all existing information on HCV infection in Croatia which will be used to advise upon preventive measures. It is estimated that 35000-45000 of the Croatian population is chronically infected with HCV. Like in other European countries, there have been changes in the HCV epidemiology in Croatia over the past few decades. In some risk groups (polytransfused and hemodialysis patients), a significant decrease in the HCV prevalence was observed after the introduction of routine HCV screening of blood/blood products in 1992. Injecting drug users (IDUs) still represent a group with the highest risk for HCV infection with prevalence ranging from 29% to 65%. Compared to the prevalence in the Croatian general population (0.9%), higher prevalence rates were found in prison populations (8.3%-44%), human immunodeficiency virus-infected patients (15%), persons with high-risk sexual behavior (4.6%) and alcohol abusers (2.4%). Low/very low prevalence was reported in children and adolescents (0.3%) as well as in blood donors (0%-0.009%). In addition, distribution of HCV genotypes has changed due to different routes of transmission. In the general population, genotypes 1 and 3 are most widely distributed (60.4%-79.8% and 12.9%-47.9%, respectively). The similar genotype distribution is found in groups with high-risk sexual behavior. Genotype 3 is predominant in Croatian IDUs (60.5%-83.9%) while in the prison population genotypes 3 and 1 are equally distributed (52.4% and 47.6%). Data on HCV prevalence and risk factors for transmission are useful for implementation of preventive measures and HCV screening.

  20. Hepatitis C Genotypes in Libya: Correlation with Patients’ Characteristics, Level of Viremia, and Degree of Liver Fibrosis

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    Abdel-Naser Elzuoki

    2017-09-01

    Full Text Available Objectives: Our study sought to determine the distribution of hepatitis C virus (HCV-genotypes among patients attending two tertiary care hospitals in Benghazi and Tripoli, Libya, and correlate this with patient’s characteristics, viral load, and degree of fibrosis. Methods: We conducted a retrospective study of 286 HCV-RNA positive Libyan patients referred from different health care facilities in east and west Libya for specific HCV treatment. HCV genotyping was carried out by gene amplification. Liver histology was graded by Metavir score according to the stage of fibrosis. Results: HCV genotypes 1, 2, 3, and 4 were found in 24.1%, 10.8%, 3.4%, and 61.5% of the patients, respectively. Genotype 4 was detected more frequently in patients from east Libya (Benghazi compared to west Libya (Tripoli (75.9% vs. 41.6%, p = 0.245. Genotype 1 was more frequent in patients from west Libya compared to east Libya (34.1% vs. 16.8%, p = 0.657. There was a significant correlation between HCV genotype distribution and viral load. Patients with genotype 4 exhibited a higher degree of liver fibrosis (p < 0.001. Conclusions: HCV genotype 4 is the predominant genotype in Libya followed by genotype 1. However, as we go from the east to the west of the country, genotype 1 increases. Genotype 4 was associated with higher level of viremia and higher stage of liver fibrosis. It is important to note that both genotypes 1 and 4 are associated with a poor response to pegylated interferon and ribavirin combination therapy. The findings emphasize the need to develop improved strategies in Libya for the successful treatment of HCV infection with novel newly available antiviral drugs.

  1. Addressing HCV infection in Europe: reported, estimated and undiagnosed cases

    DEFF Research Database (Denmark)

    Merkinaite, Simona; Lazarus, Jeff; Gore, Charles

    2008-01-01

    . At present, it is the most common cause of chronic liver disease and liver transplantation in a number of countries, with an estimated 250,000 people dying annually from HCV-related causes. Despite the magnitude of the problem, the virus does not receive adequate attention from either the general public...... or from health policy-makers. This study assesses HCV prevalence from both estimated totals and undiagnosed cases in selected European countries. Secondary sources were assessed and experts in 17 European countries were interviewed about HCV prevalence, reporting strategies and transmission. Available...

  2. Neutralizing antibodies in patients with chronic hepatitis C, genotype 1, against a panel of genotype 1 culture viruses

    DEFF Research Database (Denmark)

    Pedersen, Jannie; Jensen, Tanja B; Carlsen, Thomas H R

    2013-01-01

    , infection treated with pegylated interferon-α and ribavirin. Thirty-nine patients with chronic hepatitis C, genotype 1a or 1b, with either sustained virologic response (n = 23) or non-sustained virologic response (n = 16) were enrolled. Samples taken prior to treatment were tested for their ability...... to neutralize 6 different HCV genotype 1 cell culture recombinants (1a: H77/JFH1, TN/JFH1, DH6/JFH1; 1b: J4/JFH1, DH1/JFH1, DH5/JFH1). The results were expressed as the highest dilution yielding 50% neutralization (NAb50-titer). We observed no genotype or subtype specific differences in NAb50-titers between......The correlation of neutralizing antibodies to treatment outcome in patients with chronic hepatitis C virus (HCV) infection has not been established. The aim of this study was to determine whether neutralizing antibodies could be used as an outcome predictor in patients with chronic HCV, genotype 1...

  3. Hepatitis C virus (HCV): ever in reliable partnerships?

    African Journals Online (AJOL)

    GRACE

    2006-06-16

    Jun 16, 2006 ... hemophiliacs, multiple changes in HCV genotypes were observed in 58 % of the subjects, .... similar sources of transmission (Crockett and Keeffe,. 2005). .... tests 1 year apart. Longitudinal evaluation is also very important for ...

  4. Does hepatitis C viremia or genotype predict the risk of mortality in individuals co-infected with HIV?

    DEFF Research Database (Denmark)

    Rockstroh, Jürgen K; Peters, Lars; Grint, Daniel

    2013-01-01

    The influence of HCV-RNA levels and genotype on HCV disease progression is not well studied. The prognostic value of these markers was investigated in HIV/HCV co-infected individuals from the EuroSIDA cohort.......The influence of HCV-RNA levels and genotype on HCV disease progression is not well studied. The prognostic value of these markers was investigated in HIV/HCV co-infected individuals from the EuroSIDA cohort....

  5. Influence of hepatitis C virus and IL28B genotypes on liver stiffness.

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    Lene Fogt Lundbo

    Full Text Available Liver fibrosis has been associated with hepatitis C virus (HCV genotype and genetic variation near the interleukin 28B (IL28B gene, but the relative contribution is unknown. We aimed to investigate the relation between HCV genotypes, IL28B and development of liver stiffness.This cross-sectional study consists of 369 patients with chronic hepatitis C (CHC. Liver stiffness was evaluated using transient elastograhy (TE. Factors associated with development of liver fibrosis were identified by logistic regression analysis.We identified 369 patients with CHC. 235 were male, 297 Caucasians, and 223 had been exposed to HCV through intravenous drug use. The overall median TE value was 7.4 kPa (interquartile range (IQR 5.7-12.1. HCV replication was enhanced in patients carrying the IL28B CC genotype compared to TT and TC (5.8 vs. 5.4 log10 IU/mL, p = 0.03. Patients infected with HCV genotype 3 had significantly higher TE values (8.2 kPa; IQR, 5.9-14.5 compared to genotype 1 (6.9 kPa; IQR, 5.4-10.9 and 2 (6.7 kPa; IQR, 4.9-8.8 (p = 0.02. Within patients with genotype 3, IL28B CC genotype had the highest TE values (p = 0.04. However, in multivariate logistic regression, using various cut-off values for fibrosis and cirrhosis, only increasing age (odds ratio (OR 1.09 (95% confidence interval (CI, 1.05-1.14 per year increment, ALT (OR 1.01 (95% CI, 1.002-1.011, per unit increment and HCV genotype 3 compared to genotype 1 (OR 2.40 (95% CI, 1.19-4.81, were consistently associated with cirrhosis (TE>17.1 kPa.Age, ALT and infection with HCV genotype 3 were associated with cirrhosis assessed by TE. However, IL28B genotype was not an independent predictor of fibrosis in our study.

  6. PREVALENCE OF THE HEPATITIS C VIRUS AMONG UNIVERSITY EMPLOYEES IN SÃO PAULO, SOUTHEASTERN BRAZIL: predictive factors and geoprocessing spatial analysis

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    Cássio Vieira de OLIVEIRA

    2015-03-01

    Full Text Available Background There are limited studies on the prevalence and risk factors associated with hepatitis C virus (HCV infection. Objective Identify the prevalence and risk factors for HCV infection in university employees of the state of São Paulo, Brazil. Methods Digital serological tests for anti-HCV have been performed in 3153 volunteers. For the application of digital testing was necessary to withdraw a drop of blood through a needlestick. The positive cases were performed for genotyping and RNA. Chi-square and Fisher’s exact test were used, with P-value 40 years, blood transfusion, injectable drugs, inhalable drugs (InDU, injectable Gluconergam®, glass syringes, tattoos, hemodialysis and sexual promiscuity. Age (P=0.01, OR 5.6, CI 1.4 to 22.8, InDU (P<0.0001, OR=96.8, CI 24.1 to 388.2, Gluconergam® (P=0.0009, OR=44.4, CI 4.7 to 412.7 and hemodialysis (P=0.0004, OR=90.1, CI 7.5 – 407.1 were independent predictors. Spatial analysis of the prevalence with socioeconomic indices, Gross Domestic Product and Human Development Index by the geoprocessing technique showed no positive correlation. Conclusions The prevalence of HCV infection was 0.7%. The independent risk factors for HCV infection were age, InDU, Gluconergan® and hemodialysis. There was no spatial correlation of HCV prevalence with local economic factors.

  7. HIV infection and hepatitis C virus genotype 1a are associated with phylogenetic clustering among people with recently acquired hepatitis C virus infection.

    Science.gov (United States)

    Bartlett, Sofia R; Jacka, Brendan; Bull, Rowena A; Luciani, Fabio; Matthews, Gail V; Lamoury, Francois M J; Hellard, Margaret E; Hajarizadeh, Behzad; Teutsch, Suzy; White, Bethany; Maher, Lisa; Dore, Gregory J; Lloyd, Andrew R; Grebely, Jason; Applegate, Tanya L

    2016-01-01

    The aim of this study was to identify factors associated with phylogenetic clustering among people with recently acquired hepatitis C virus (HCV) infection. Participants with available sample at time of HCV detection were selected from three studies; the Australian Trial in Acute Hepatitis C, the Hepatitis C Incidence and Transmission Study - Prison and Community. HCV RNA was extracted and Core to E2 region of HCV sequenced. Clusters were identified from maximum likelihood trees with 1000 bootstrap replicates using 90% bootstrap and 5% genetic distance threshold. Among 225 participants with available Core-E2 sequence (ATAHC, n=113; HITS-p, n=90; and HITS-c, n=22), HCV genotype prevalence was: G1a: 38% (n=86), G1b: 5% (n=12), G2a: 1% (n=2), G2b: 5% (n=11), G3a: 48% (n=109), G6a: 1% (n=2) and G6l 1% (n=3). Of participants included in phylogenetic trees, 22% of participants were in a pair/cluster (G1a-35%, 30/85, mean maximum genetic distance=0.031; G3a-11%, 12/106, mean maximum genetic distance=0.021; other genotypes-21%, 6/28, mean maximum genetic distance=0.023). Among HCV/HIV co-infected participants, 50% (18/36) were in a pair/cluster, compared to 16% (30/183) with HCV mono-infection (P=infection [vs. HCV mono-infection; adjusted odds ratio (AOR) 4.24; 95%CI 1.91, 9.39], and HCV G1a infection (vs. other HCV genotypes; AOR 3.33, 95%CI 0.14, 0.61).HCV treatment and prevention strategies, including enhanced antiviral therapy, should be optimised. The impact of targeting of HCV treatment as prevention to populations with higher phylogenetic clustering, such as those with HIV co-infection, could be explored through mathematical modelling. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Comparative study of patients with chronic hepatitis C virus infection due to genotypes 1 and 3 referred for treatment in southeast Brazil

    Directory of Open Access Journals (Sweden)

    Gonçales Fernando L

    2008-12-01

    Full Text Available Abstract Background The progression of liver disease in patients with chronic hepatitis C virus (HCV infection is influenced by host and viral factors. Distinct clinical outcomes in patients infected with different HCV genotypes have been described in the literatute. However, the association between specific HCV genotype and clinical outcome remains unclear. We set out to study the natural history of HCV genotype 1 and 3 infections in Campinas, São Paulo state, Brazil, focusing on epidemiological, clinical, biochemical, and histological characteristics. Methods Patients with HCV infection referred for treatment between January 2003 and December 2006 were included in this study. We collected epidemiological, clinical, and laboratorial data using standard forms. Results A total of 283 patients were included; genotype 1 was idenfied in 163 (57.6% patients, genotype 3 in 112 (39.6%, genotype 2 in 7 (2.5%, and genotype 4 in 1 (0.35%. Patients with genotype 2 and 4 were excluded from analysis. Multivariate analysis showed that intravenous energetic drug, positive cryoglobulin, and cirrhosis were independently and significantly associated with HCV genotype 3 (p Conclusion Genotype 3 currently seems to be associated with intravenous energetic drug, high frequency of cryoglobulinemia, and advanced liver disease in our region. Understanding the distribution of the different HCV genotypes can elucidate transmission of HCV and support optimal prevention strategies.

  9. HOMA-AD in Assessing Insulin Resistance in Lean Noncirrhotic HCV Outpatients.

    Science.gov (United States)

    Michalczuk, Matheus Truccolo; Kappel, Camila Rippol; Birkhan, Oscar; Bragança, Ana Carolina; Alvares-da-Silva, Mário Reis

    2012-01-01

    Introduction. There is an association between HCV and insulin resistance (IR), which is currently assessed by HOMA-IR. There is evidence that HOMA-adiponectin (HOMA-AD) is more accurate, but its role in HCV patients is unknown. The purpose of this study was to evaluate IR in an HCV sample and controls, in order to compare the accuracy of HOMA-IR and HOMA-AD. Methods. Ninety-four HCV outpatients aged IR was estimated by HOMA-IR and HOMA-AD. Results. The groups were similar regarding sex and BMI, but the HCV patients were older. The median insulin level was higher in the HCV group (8.6 mU/mL (6.5-13.7) versus 6.5 (4.3-10.7), P = 0.004), as was median HOMA-IR (1.94 (1.51 to 3.48) versus 1.40 (1.02 to 2.36), P = 0.002) and the prevalence of IR (38.3% versus 10.3% (P = 0.009)). No differences were found in adiponectin levels (P = 0.294) and HOMA-AD (P = 0.393). Conclusion. IR is highly prevalent even in low-risk HCV outpatients. Adiponectin is not influenced by the presence of HCV. HOMA-AD does not seem to be useful in assessing IR in HCV patients.

  10. Hepatitis C virus genotypes among multiply transfused hemoglobinopathy patients from Northern Iraq

    Directory of Open Access Journals (Sweden)

    Adil A Othman

    2014-01-01

    Full Text Available Background and Aim: Owing to the scarcity of data on hepatitis C virus (HCV genotypes in Iraq and due to their epidemiological as well as therapy implications, this study was initiated aiming at determining these genotypes in Northern Iraq. Materials and Methods: A total of 70 HCV antibody positive multi transfused patients with hemoglobinopathies, who had detectable HCV ribonucleic acid, were recruited for genotyping using genotype-specific nested polymerase chain reaction. Results: The most frequent genotype detected was genotype 4 (52.9% followed by 3a (17.1%, 1b (12.9% and 1a (1.4%, while mixed genotypes (4 with either 3a or 1b were detected in 7.1%. Conclusion: The predominance of genotype 4 is similar to other studies from surrounding Eastern Mediterranean Arab countries and to the only earlier study from central Iraq, however the significant high proportion of 3a and scarcity of 1a, are in contrast to the latter study and may be explainable by the differing population interactions in this part of Iraq. This study complements previous studies from Eastern Mediterranean region and demonstrates relative heterogeneity of HCV genotype distribution within Iraq and should trigger further studies in other parts of the country.

  11. Ribavirin Concentrations Do Not Predict Sustained Virological Response in HIV/HCV-Coinfected Patients Treated with Ribavirin and Pegylated Interferon in the Swiss HIV Cohort Study.

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    Helen Kovari

    Full Text Available Ribavirin (RBV is an essential component of most current hepatitis C (HCV treatment regimens and still standard of care in the combination with pegylated interferon (pegIFN to treat chronic HCV in resource limited settings. Study results in HIV/HCV-coinfected patients are contradicting as to whether RBV concentration correlates with sustained virological response (SVR.We included 262 HCV treatment naïve HIV/HCV-coinfected Swiss HIV Cohort Study (SHCS participants treated with RBV and pegIFN between 01.01.2001-01.01.2010, 134 with HCV genotype (GT 1/4, and 128 with GT 2/3 infections. RBV levels were measured retrospectively in stored plasma samples obtained between HCV treatment week 4 and end of therapy. Uni- and multivariable logistic regression analyses were used to evaluate the association between RBV concentration and SVR in GT 1/4 and GT 2/3 infections. The analyses were repeated stratified by treatment phase (week 4-12, 13-24, >24 and IL28B genotype (CC versus CT/TT.SVR rates were 35.1% in GT 1/4 and 70.3% in GT 2/3 infections. Overall, median RBV concentration was 2.0 mg/L in GT 1/4, and 1.9 mg/L in GT 2/3, and did not change significantly across treatment phases. Patients with SVR had similar RBV concentrations compared to patients without SVR in both HCV genotype groups. SVR was not associated with RBV levels ≥2.0 mg/L (GT 1/4, OR 1.19 [0.5-2.86]; GT 2/3, 1.94 [0.78-4.80] and ≥2.5 mg/L (GT 1/4, 1.56 [0.64-3.84]; GT 2/3 2.72 [0.85-8.73], regardless of treatment phase, and IL28B genotype.In HIV/HCV-coinfected patients treated with pegIFN/RBV, therapeutic drug monitoring of RBV concentrations does not enhance the chance of HCV cure, regardless of HCV genotype, treatment phase and IL28B genotype.

  12. Robust hepatitis C genotype 3a cell culture releasing adapted intergenotypic 3a/2a (S52/JFH1) viruses

    DEFF Research Database (Denmark)

    Gottwein, J.M.; Scheel, Troels Kasper Høyer; Hoegh, A.M.

    2007-01-01

    BACKGROUND & AIMS: Recently, full viral life cycle hepatitis C virus (HCV) cell culture systems were developed for strain JFH1 (genotype 2a) and an intragenotypic 2a/2a genome (J6/JFH). We aimed at exploiting the unique JFH1 replication characteristics to develop culture systems for genotype 3a......, which has a high prevalence worldwide. METHODS: Huh7.5 cells were transfected with RNA transcripts of an intergenotypic 3a/JFH1 recombinant with core, E1, E2, p7, and NS2 of the 3a reference strain S52, and released viruses were passaged. Cultures were examined for HCV core and/or NS5A expression...... (immunostaining), HCV RNA titers (real-time PCR), and infectivity titers (50% tissue culture infectious dose). The role of mutations identified by sequencing of recovered S52/JFH1 viruses was analyzed by reverse genetics studies. RESULTS: S52/JFH1 and J6/JFH viruses passaged in Huh7.5 cells showed comparable...

  13. Hepatitis C virus genotypes in Singapore and Indonesia.

    Science.gov (United States)

    Ng, W C; Guan, R; Tan, M F; Seet, B L; Lim, C A; Ngiam, C M; Sjaifoellah Noer, H M; Lesmana, L

    1995-01-01

    5' untranslated and partial core (C) region sequence of hepatitis C virus (HCV) in 21 Singaporean and 15 Indonesian isolates were amplified by reverse-transcription polymerase chain reaction and sequenced with the use of conserved primer sequences deduced from HCV genomes identified in other geographical regions. The HCV genotypes are predominantly that of Simmonds type 1 and less of type 2 and 3 with the latter genotype currently not detected in Indonesia. The 5' untranslated sequences are related to HCV-1. DK-7 (Denmark), US-11 (United States of America), HCV-J4, SA-10 (South Africa), T-3 (Taiwan), HCV-J6, HCV-J8, Eb-1 and Eb-8. When compared with the prototype HCV-1, insertions are found within the 5' untranslated region of Singaporean isolates and not in the Indonesians. There are Singaporean and Indonesian isolates that have sequences within the 5' untranslated region that differ slightly from each other. Microheterogeneity is observed in the core region of two Singaporeans and one Indonesian isolate. Finally, not all HCV isolates can be amplified with the conserved core sequence primers when compared with the ease with which these isolates can be amplified with 5' untranslated region conserved primers.

  14. Efficacy of sofosbuvir plus ribavirin with or without peginterferon-alfa in patients with hepatitis C virus genotype 3 infection and treatment-experienced patients with cirrhosis and hepatitis C virus genotype 2 infection.

    Science.gov (United States)

    Foster, Graham R; Pianko, Stephen; Brown, Ashley; Forton, Daniel; Nahass, Ronald G; George, Jacob; Barnes, Eleanor; Brainard, Diana M; Massetto, Benedetta; Lin, Ming; Han, Bin; McHutchison, John G; Subramanian, G Mani; Cooper, Curtis; Agarwal, Kosh

    2015-11-01

    We conducted an open-label, randomized, phase 3 trial to determine the efficacy and safety of sofosbuvir and ribavirin, with and without peginterferon-alfa, in treatment-experienced patients with cirrhosis and hepatitis C virus (HCV) genotype 2 infection and treatment-naïve or treatment-experienced patients with HCV genotype 3 infection. The study was conducted at 80 sites in Europe, North America, Australia, and New Zealand Patients were randomly assigned (1:1:1) to groups given sofosbuvir and ribavirin for 16 weeks (n = 196); sofosbuvir and ribavirin for 24 weeks (n = 199); or sofosbuvir, peginterferon-alfa, and ribavirin for 12 weeks (n = 197). The primary end point was the percentage of patients with HCV RNA <15 IU/mL 12 weeks after stopping therapy (sustained virologic response [SVR12]). From October 2013 until April 2014, we enrolled and treated 592 patients-48 with genotype 2 HCV and compensated cirrhosis who had not achieved SVR with previous treatments and 544 with genotype 3 HCV (279 treatment-naïve and 265 previously treated). Overall, 219 patients (37%) had compensated cirrhosis. The last post-treatment week 12 patient visit was in January 2015. Rates of SVR12 among patients with genotype 2 HCV were 87% and 100%, for those receiving 16 and 24 weeks of sofosbuvir and ribavirin, respectively, and 94% for those receiving sofosbuvir, peginterferon, and ribavirin for 12 weeks. Rates of SVR12 among patients with genotype 3 HCV were 71% and 84% in those receiving 16 and 24 weeks of sofosbuvir and ribavirin, respectively, and 93% in those receiving sofosbuvir, peginterferon, and ribavirin. On-treatment virologic failure occurred in 3 patients with HCV genotype 3a receiving sofosbuvir and ribavirin for 24 weeks. The most common adverse events were fatigue, headache, insomnia, and nausea. Overall, 1% of patients discontinued treatment due to adverse events. Among patients with genotype 3 HCV infection, including a large proportion of treatment

  15. Seroprevalence of HBV, HCV & HIV co-infection and risk factors analysis in Tripoli-Libya.

    Directory of Open Access Journals (Sweden)

    Mohamed A Daw

    Full Text Available In 1998 Libya experienced a major outbreak of multiple blood borne viral hepatitis and HIV infections. Since then, no studies have been done on the epidemic features and risk factors of HBV, HCV, HIV and co-infection among the general population.A prospective study was carried out using a multi-centre clustering method to collect samples from the general population. The participants were interviewed, and relevant information was collected, including socio-demographic, ethnic, and geographic variables. This information was correlated with the risk factors involved in the transmission of HBV, HCV and HIV. Blood samples were collected and the sera were tested for HBsAg, anti-HCV and anti-HIV using enzyme immunoassay.A total of 9,170 participants from the nine districts of Tripoli were enrolled. The average prevalence of HBsAg was 3.7%, anti-HCV 0.9%, anti-HIV 0.15% and co-infection 0.02%. The prevalence varied from one district to another. HBV was more prevalent among those aged over 50 years and was associated with family history. Anti-HCV and anti-HIV were more prevalent among those aged 20-40 years. Intravenous drug use and blood transfusion were the main risk factors for HCV and HIV infection.HBV, HCV, HIV and co-infection are relatively common in Libya. High prevalence was associated with geographic, ethnic and socioeconomic variability within the community. HCV and HIV infections among the younger age groups are becoming an alarming issue. Regulations and health care education need to be implemented and longer term follow-up should be planned.

  16. Performance characteristics of the ARCHITECT anti-HCV assay.

    Science.gov (United States)

    Jonas, Gesa; Pelzer, Claudia; Beckert, Christian; Hausmann, Michael; Kapprell, Hans-Peter

    2005-10-01

    The ARCHITECT Anti-HCV assay is a fully automated high throughput chemiluminescent microparticle immunoassay (CMIA) for the detection of antibodies to structural and nonstructural proteins of the hepatitis C virus (HCV). To further enhance the performance of this test, the assay was modified to improve the specificity for blood donor specimens. The specificity of the enhanced ARCHITECT Anti-HCV assay was evaluated by screening blood donor samples randomly collected from various German blood banks, as well as hospitalized patient samples derived from Germany and the US. Additionally, antibody sensitivity was determined on commercially available anti-HCV seroconversion panels and on a commercially available worldwide anti-HCV genotype performance panel. Apparent specificity of the modified ARCHITECT Anti-HCV assay in a blood donor population consisting of 3811 specimens was 99.92%, compared to 99.76% for the current on-market assay. Additionally, antibody sensitivity was determined on commercially available anti-HCV seroconversion panels. Seroconversion sensitivity equivalent to or better than the current on-market product was observed by testing 33 seroconversion panels. This study demonstrates that the modified version of the ARCHITECT Anti-HCV assay shows improved specificity for blood donor specimens compared to the current assay on market without compromising sensitivity. With the availability of the improved ARCHITECT Anti-HCV assay and the recent launch of the ARCHITECT HIV Ag/Ab Combo assay, the ARCHITECT system now offers a full hepatitis/retrovirus menu with excellent performance on a high throughput, random access, automated analyzer, ideally suited for blood screening and diagnostic applications.

  17. Hepatitis C Virus Genotype 1 to 6 Protease Inhibitor Escape Variants: In Vitro Selection, Fitness, and Resistance Patterns in the Context of the Infectious Viral Life Cycle.

    Science.gov (United States)

    Serre, Stéphanie B N; Jensen, Sanne B; Ghanem, Lubna; Humes, Daryl G; Ramirez, Santseharay; Li, Yi-Ping; Krarup, Henrik; Bukh, Jens; Gottwein, Judith M

    2016-06-01

    Hepatitis C virus (HCV) NS3 protease inhibitors (PIs) are important components of novel HCV therapy regimens. Studies of PI resistance initially focused on genotype 1. Therefore, knowledge about the determinants of PI resistance for the highly prevalent genotypes 2 to 6 remains limited. Using Huh7.5 cell culture-infectious HCV recombinants with genotype 1 to 6 NS3 protease, we identified protease positions 54, 155, and 156 as hot spots for the selection of resistance substitutions under treatment with the first licensed PIs, telaprevir and boceprevir. Treatment of a genotype 2 isolate with the newer PIs vaniprevir, faldaprevir, simeprevir, grazoprevir, paritaprevir, and deldeprevir identified positions 156 and 168 as hot spots for resistance; the Y56H substitution emerged for three newer PIs. Substitution selection also depended on the specific recombinant. The substitutions identified conferred cross-resistance to several PIs; however, most substitutions selected under telaprevir or boceprevir treatment conferred less resistance to certain newer PIs. In a single-cycle production assay, across genotypes, PI treatment primarily decreased viral replication, which was rescued by PI resistance substitutions. The substitutions identified resulted in differential effects on viral fitness, depending on the original recombinant and the substitution. Across genotypes, fitness impairment induced by resistance substitutions was due primarily to decreased replication. Most combinations of substitutions that were identified increased resistance or fitness. Combinations of resistance substitutions with fitness-compensating substitutions either rescued replication or compensated for decreased replication by increasing assembly. This comprehensive study provides insight into the selection patterns and effects of PI resistance substitutions for HCV genotypes 1 to 6 in the context of the infectious viral life cycle, which is of interest for clinical and virological HCV research

  18. Prevalence and genotypes of Enterocytozoon bieneusi in China.

    Science.gov (United States)

    Wang, Sha-Sha; Wang, Rong-Jun; Fan, Xian-Cheng; Liu, Ting-Li; Zhang, Long-Xian; Zhao, Guang-Hui

    2018-07-01

    Enterocytozoon bieneusi has been considered as the most frequently diagnosed microsporidian species in humans and various animal species, accounting for more than 90% of the cases of human microsporidiosis. Spores of this pathogen excreted from both symptomatic and asymptomatic hosts into environment also would be an important source of waterborne outbreak of microsporidiosis. Due to limited effective drugs available but with too much side effects to mammals (eg. toxic), accurate characterization of E. bieneusi in both humans and animals is essential to implement effective control strategies to this pathogen. In China, E. bieneusi infection was presented in humans and some animals with high prevalence. Analysis of genetic variations of the internal transcribed spacer (ITS) sequences found 361 genotypes in China, and some novel genotypes were identified in some specific hosts. Additionally, associations between infections and some risk factors were also observed. In the present article, we reviewed the current status of prevalence, genotypes, multilocus genotypes (MLGs) in humans, various animals and waters in China. These findings will provide basic information for developing effective control strategies against E. bieneusi infection in China as well as other countries. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. HCV viraemia in anti-HCV-negative haemodialysis patients: Do we need HCV RNA detection test?

    Science.gov (United States)

    Papadopoulos, Nikolaos; Griveas, Ioannis; Sveroni, Eirini; Argiana, Vasiliki; Kalliaropoulos, Antonios; Martinez-Gonzalez, Beatriz; Deutsch, Melanie

    2018-03-01

    Hepatitis C virus (HCV) infection is still common among dialysis patients, but the natural history of HCV in this group is not completely understood. The KDIGO HCV guidelines of 2009 recommend that chronic haemodialysis patients be screened for HCV antibody upon admission to the dialysis clinic and every 6 months thereafter if susceptible to HCV infection. However, previous studies have shown the presence of HCV viraemia in anti-HCV-negative haemodialysis patients as up to 22%. To evaluate the presence of HCV viraemia, using HCV RNA detection, among anti-HCV-negative haemodialysis patients from a tertiary dialysis unit in Athens. We enrolled 41 anti-HCV-negative haemodialysis patients diagnosed with third-generation enzyme immunoassay. HCV viraemia was evaluated using a sensitive (cut-off: 12 IU/mL) reverse transcriptase polymerase chain reaction (COBAS AmpliPrep/TaqMan system) for HCV RNA. None of the 41 anti-HCV-negative haemodialysis patients were shown to be viraemic. Routine HCV RNA testing appears not to be necessary in anti-HCV-negative haemodialysis patients.

  20. Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics.

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    Min Chen

    Full Text Available The human immunodeficiency virus 1 (HIV-1 epidemic in China historically stemmed from intravenous drug users (IDUs in Yunnan. Due to a shared transmission route, hepatitis C virus (HCV/HIV-1 co-infection is common. Here, we investigated HCV genetic characteristics and baseline drug resistance among HIV-infected IDUs in Yunnan.Blood samples of 432 HIV-1/HCV co-infected IDUs were collected from January to June 2014 in six prefectures of Yunnan Province. Partial E1E2 and NS5B genes were sequenced. Phylogenetic, evolutionary and genotypic drug resistance analyses were performed.Among the 293 specimens successfully genotyped, seven subtypes were identified, including subtypes 3b (37.9%, 111/293, 3a (21.8%, 64/293, 6n (14.0%, 41/293, 1b (10.6%, 31/293, 1a (8.2%, 24/293, 6a (5.1%, 15/293 and 6u (2.4%, 7/293. The distribution of HCV subtypes was mostly related to geographic location. Subtypes 3b, 3a, and 6n were detected in all six prefectures, however, the other four subtypes were detected only in parts of the six prefectures. Phylogeographic analyses indicated that 6n, 1a and 6u originated in the western prefecture (Dehong and spread eastward and showed genetic relatedness with those detected in Burmese. However, 6a originated in the southeast prefectures (Honghe and Wenshan bordering Vietnam and was transmitted westward. These subtypes exhibited different evolutionary rates (between 4.35×10-4 and 2.38×10-3 substitutions site-1 year-1 and times of most recent common ancestor (tMRCA, between 1790.3 and 1994.6, suggesting that HCV was multiply introduced into Yunnan. Naturally occurring resistance-associated mutations (C316N, A421V, C445F, I482L, V494A, and V499A to NS5B polymerase inhibitors were detected in direct-acting antivirals (DAAs-naïve IDUs.This work reveals the temporal-spatial distribution of HCV subtypes and baseline HCV drug resistance among HIV-infected IDUs in Yunnan. The findings enhance our understanding of the characteristics and

  1. HCV Transmission between serodiscordant couples through sexual route

    International Nuclear Information System (INIS)

    Khan, R.S.A.; Khalid, S.R.; Naseer, M.; Mirza, R.

    2014-01-01

    To determine the rate of transmission of HCV between n spouses through sexual route. Study Design: Descriptive study. Place and Duration of Study: This study was carried out at Military Hospital, Rawalpindi, Pakistan. It was conducted over a period of 4 years from June 2009 to June 2013. Patients and Methods: One hundred and sixty eight consecutive patients confirmed to have HCV infection by PCR for HCV RNA were enrolled in the study. Their spouses were also included in the study, and it was established through PCR for HCV RNA that the spouses were not suffering from HCV infection. All couples were inducted in the study within the first two months of starting the study. Therefore, the maximum and minimum follow-up time was 48 months and 46 months, respectively. The spouses were questioned for HCV risk factors and were tested for HCV antibodies six monthly. Once spouses were found to be anti-HCV positive, their HCV status was confirmed with PCR for HCV RNA. Results: Out of 168 patients, 90 (53.57%) were males and 78 (46.43%) were females. PCR for HCV RNA was found to be positive in 4 of 168 (2.38%) spouses. All the se 4 couples in whom HCV transmission was found had genotype 3a. Out of the 4 spouses who tested positive for HCV RNA PCR, 3 (75%) were females and 1 (25%) was male. So HCV infection was transmitted in 3 out of 90 (3.33 %) and 1 out of 78 (1.28%) female and male spouses, respectively. In PCR for HCV RNA positive and negative spouses, the duration of marriage was 202 +- 53 and 199 +- 49 weeks; and the number of total sexual intercourses was 171 +- 93 and 169 +- 89, respectively. Conclusion: HCV transmission among serodiscordant couples in our setup did occur. The overall rate of transmission was 2.38%. The rate of transmission from male to female (3.33%) was higher than female to male (1.28%). However, a large scale study conducted over a longer duration of time is needed to recommend protected sex in serodiscordant couples if either partner is suffering

  2. An autochthonous case of hepatitis C virus genotype 5a in Brazil: phylogenetic analysis

    DEFF Research Database (Denmark)

    Ribeiro, L.C.; Souto, F.J.D.; do Espirito-Santo, M.P.

    2009-01-01

    Genotype 5 of hepatitis C virus (HCV) has been rarely identified in South America. A female of African descent who never left Brazil was found to be infected by this genotype in Mato Grosso state, Central Brazil. The patient denied drug injections and revealed that she had received blood...... transfusions several years before. One of her blood donors was identified and tested negative for anti-HCV and HCV RNA, as were her husband and offspring. Phylogenetic analysis of the E1 and NS5B regions confirmed that this HCV strain belonged to genotype 5a. However, the E1 region analysis indicates that our...

  3. Drug treatment program patients' hepatitis C virus (HCV education needs and their use of available HCV education services

    Directory of Open Access Journals (Sweden)

    Osborne Andrew

    2007-03-01

    Full Text Available Abstract Background In spite of the disproportionate prevalence of hepatitis C virus (HCV infection among drug users, many remain uninformed or misinformed about the virus. Drug treatment programs are important sites of opportunity for providing HCV education to their patients, and many programs do, in fact, offer this education in a variety of formats. Little is known, however, about the level of HCV knowledge among drug treatment program patients, and the extent to which they utilize their programs' HCV education services. Methods Using data collected from patients (N = 280 in 14 U.S. drug treatment programs, we compared patients who reported that they never injected drugs (NIDUs with past or current drug injectors (IDUs concerning their knowledge about HCV, whether they used HCV education opportunities at their programs, and the facilitators and barriers to doing so. All of the programs were participating in a research project that was developing, implementing, and evaluating a staff training to provide HCV support to patients. Results Although IDUs scored higher on an HCV knowledge assessment than NIDUs, there were many gaps in HCV knowledge among both groups of patients. To address these knowledge gaps, all of the programs offered at least one form of HCV education: all offered 1:1 sessions with staff, 12 of the programs offered HCV education in a group format, and 11 of the programs offered this education through pamphlets/books. Only 60% of all of the participating patients used any of their programs' HCV education services, but those who did avail themselves of these HCV education opportunities generally assessed them positively. In all, many patients were unaware that HCV education was offered at their programs through individual sessions with staff, group meetings, and books/pamphlets, (42%, 49%, and 46% of the patients, respectively, and 22% were unaware that any HCV education opportunities existed. Conclusion Efforts especially need

  4. Are RA patients from a non-endemic HCV population screened for HCV? A cross-sectional analysis of three different settings.

    Science.gov (United States)

    Skinner-Taylor, Cassandra Michelle; Erhard-Ramírez, Alejandro; Garza-Elizondo, Mario Alberto; Esquivel-Valerio, Jorge Antonio; Abud-Mendoza, Carlos; Martínez-Martínez, Marco Ulises; Vega-Morales, David; Arana-Guajardo, Ana

    In Mexico, other risk factors are associated with hepatitis C virus (HCV): prior heroin users, living alone, widower, and northern region residence. Rheumatoid arthritis (RA) patients are considered immunosuppressed and HCV testing is recommended before treatment. The aim of the study was to describe the characteristics of HCV testing in RA patients in three different medical care settings in a non-endemic area. A retrospective observational study was performed using medical records from 960 RA patients describing the indications for HCV testing. The test was performed in 28.6% and the HCV overall frequency was 0.36%. Population characteristics were not associated with an increased risk of HCV infection; therefore, anti-HCV positivity was low. The main reason for testing was before starting biological agents. Due to the low pre-test probability, testing for HCV infection should be personalized; i.e., according to disease prevalence in a particular geographical location and the individual risk factors. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  5. Seroprevalence of HBV, HCV & HIV Co-Infection and Risk Factors Analysis in Tripoli-Libya

    Science.gov (United States)

    Daw, Mohamed A.; Shabash, Amira; El-Bouzedi, Abdallah; Dau, Aghnya A.

    2014-01-01

    Background In 1998 Libya experienced a major outbreak of multiple blood borne viral hepatitis and HIV infections. Since then, no studies have been done on the epidemic features and risk factors of HBV, HCV, HIV and co-infection among the general population. Methods A prospective study was carried out using a multi-centre clustering method to collect samples from the general population. The participants were interviewed, and relevant information was collected, including socio-demographic, ethnic, and geographic variables. This information was correlated with the risk factors involved in the transmission of HBV, HCV and HIV. Blood samples were collected and the sera were tested for HBsAg, anti-HCV and anti-HIV using enzyme immunoassay. Results A total of 9,170 participants from the nine districts of Tripoli were enrolled. The average prevalence of HBsAg was 3.7%, anti-HCV 0.9%, anti-HIV 0.15% and co-infection 0.02%. The prevalence varied from one district to another. HBV was more prevalent among those aged over 50 years and was associated with family history. Anti-HCV and anti-HIV were more prevalent among those aged 20–40 years. Intravenous drug use and blood transfusion were the main risk factors for HCV and HIV infection. Conclusion HBV, HCV, HIV and co-infection are relatively common in Libya. High prevalence was associated with geographic, ethnic and socioeconomic variability within the community. HCV and HIV infections among the younger age groups are becoming an alarming issue. Regulations and health care education need to be implemented and longer term follow-up should be planned. PMID:24936655

  6. Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II).

    Science.gov (United States)

    Zeuzem, S; Flisiak, R; Vierling, J M; Mazur, W; Mazzella, G; Thongsawat, S; Abdurakhmanov, D; Van Kính, N; Calistru, P; Heo, J; Stanciu, C; Gould, M; Makara, M; Hsu, S-J; Buggisch, P; Samuel, D; Mutimer, D; Nault, B; Merz, M; Bao, W; Griffel, L H; Brass, C; Naoumov, N V

    2015-10-01

    Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection. Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy. A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension. Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens. © 2015 John Wiley & Sons Ltd.

  7. Analysis of in vitro replicated human hepatitis C virus (HCV for the determination of genotypes and quasispecies

    Directory of Open Access Journals (Sweden)

    Chelyapov Nickolas

    2006-09-01

    Full Text Available Abstract Isolation and self-replication of infectious HCV has been a difficult task. However, this is needed for the purposes of developing rational drugs and for the analysis of the natural virus. Our recent report of an in vitro system for the isolation of human HCV from infected patients and their replication in tissue culture addresses this challenge. At California Institute of Molecular Medicine several isolates of HCV, called CIMM-HCV, were grown for over three years in cell culture. This is a report of the analysis of CIMM-HCV isolates for subtypes and quasispecies using a 269 bp segment of the 5'UTR. HCV RNA from three patients and eleven CIMM-HCV were analyzed for this purpose. All isolates were essentially identical. Isolates of HCV from one patient were serially transmitted into fresh cells up to eight times and the progeny viruses from each transmission were compared to each other and also to the primary isolates from the patient's serum. Some isolates were also transmitted to different cell types, while others were cultured continuously without retransmission for over three years. We noted minor sequence changes when HCV was cultured for extended periods of time. HCV in T-cells and non-committed lymphoid cells showed a few differences when compared to isolates obtained from immortalized B-cells. These viruses maintained close similarity despite repeated transmissions and passage of time. There were no subtypes or quasispecies noted in CIMM-HCV.

  8. Variety of genotypes of a HCV virus and outcomes of chronic hepatitis C: results 5 summer supervision in the territory of the Kirov region

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    S. V. Baramzina

    2013-01-01

    Full Text Available The analysis of the epidemiological situation in respect of chronic hepatitis C in the Russian Federation and the Kirov region for the period 1998–2012 yy. The data on the characteristics and frequency of outcomes of chronic hepatitis C, according to the 5-year observation of patients Kirov branch of viral hepatitis infectious diseases hospital. The results of genotyping HCV-virus in 730 patients with chronic hepatitis C in the dynamics from 2006–2010, and in comparison with other regions of Russia. Dominant in the region are the genotypes 1b and 3a, minor – 2 and 1a. During the analyzed period, there was a trend to a decrease in the proportion of genotypes 1b and 1a, and increase the proportion of subtype 3a and 2.

  9. [Clinical benefit of HCV core antigen assay in patients receiving interferon and ribavirin combination therapy].

    Science.gov (United States)

    Higashimoto, Makiko; Takahashi, Masahiko; Jokyu, Ritsuko; Saito, Hidetsugu

    2006-02-01

    A highly sensitive second generation HCV core antigen assay has recently been developed. We compared viral disappearance and kinetics data between commercially available core antigen assays, Lumipulse Ortho HCV Ag, and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor Test, Version 2 to estimate the predictive benefit of sustained viral response (SVR) and non-SVR in 59 patients treated with interferon and ribavirin combination therapy. We found a good correlation between HCV core Ag and HCV RNA level regardless of genotype. Although the sensitivity of the core antigen assay was lower than PCR, the dynamic range was broader than that of the PCR assay, so that we did not need to dilute the samples in 59 patients. We detected serial decline of core Ag levels in 24 hrs, 7 days and 14 days after interferon combination therapy. The decline of core antigen levels was significant in SVR patients compared to non-SVR as well as in genotype 2a, 2b patients compared to 1b. Core antigen-negative on day 1 could predict all 10 SVR patients (PPV = 100%), whereas RNA-negative could predict 22 SVR out of 25 on day 14 (PPV = 88.0%). None of the patients who had detectable serum core antigen on day 14 became SVR(NPV = 100%), although NPV was 91.2% on RNA negativity. An easy, simple, low cost new HCV core antigen detecting system seems to be useful for assessing and monitoring IFN treatment for HCV.

  10. A cross-sectional study of hepatitis C among people living with HIV in Cambodia: Prevalence, risk factors, and potential for targeted screening.

    Directory of Open Access Journals (Sweden)

    Anja De Weggheleire

    Full Text Available The epidemiology of hepatitis C in Cambodia is not well-known. We evaluated the prevalence of hepatitis C virus (HCV and risk factors in the HIV cohort of Sihanouk Hospital Center of Hope in Phnom Penh to strengthen the evidence for suitable HCV testing strategies among people living with HIV (PLWH in Cambodia. All consenting adult PLWH without a history of HCV treatment were tested for HCV between November 2014 and May 2016 according to the CDC algorithm (HCV antibody II electro-chemiluminescence immunoassay, followed by COBAS® AmpliPrep/COBAS® TaqMan® HCV PCR and INNO-LIA® HCV Score immunoblot end-testing. Genotyping was performed using the line probe assay Versant HCV genotype 2.0®. The study enrolled a total of 3045 patients (43% males, median age: 42.5 years, 55 years (11.2%. Genotype 1b (45% and 6 (41% were predominant. Coinfected patients had a higher aspartate-to-platelet ratio index, lower platelets, a lower HBsAg positivity rate and more frequent diabetes. Based on logistic regression, blood transfusion antecedents (adjusted odds ratio 2.9; 95% CI 1.7-4.9, unsafe medical injections (2.0; 1.3-3.2, and partner (3.4; 1.5-7.6 or household member (2.4; 1.3-3.2 with liver disease were independently associated with HCV in women. However, having a tattoo/scarification (1.9; 1.1-3.4 and household member (3.1; 1.3-7.3 with liver disease were associated with HCV in men. Thus, our study found intermediate endemicity of active hepatitis C in a large Cambodian HIV cohort and provides initial arguments for targeted HCV screening (>50 years, partner/household member with liver disease, diabetes, increased aspartate-to-platelet ratio index as efficient way forward.

  11. Correlation between pre-treatment quasispecies complexity and treatment outcome in chronic HCV genotype 3a.

    LENUS (Irish Health Repository)

    Moreau, Isabelle

    2012-02-03

    Pre-treatment HCV quasispecies complexity and diversity may predict response to interferon based anti-viral therapy. The objective of this study was to retrospectively (1) examine temporal changes in quasispecies prior to the start of therapy and (2) investigate extensively quasispecies evolution in a group of 10 chronically infected patients with genotype 3a, treated with pegylated alpha2a-Interferon and ribavirin. The degree of sequence heterogeneity within the hypervariable region 1 was assessed by analyzing 20-30 individual clones in serial serum samples. Genetic parameters, including amino acid Shannon entropy, Hamming distance and genetic distance were calculated for each sample. Treatment outcome was divided into (1) sustained virological responders (SVR) and (2) treatment failure (TF). Our results indicate, (1) quasispecies complexity and diversity are lower in the SVR group, (2) quasispecies vary temporally and (3) genetic heterogeneity at baseline can be use to predict treatment outcome. We discuss the results from the perspective of replicative homeostasis.

  12. Flunarizine Prevents Hepatitis C Virus Membrane Fusion in a Genotype-dependent Manner by Targeting the Potential Fusion Peptide within E1

    Science.gov (United States)

    Perin, Paula M.; Haid, Sibylle; Brown, Richard J. P.; Doerrbecker, Juliane; Schulze, Kai; Zeilinger, Carsten; von Schaewen, Markus; Heller, Brigitte; Vercauteren, Koen; Luxenburger, Eva; Baktash, Yasmine M.; Vondran, Florian W. R.; Speerstra, Sietkse; Awadh, Abdullah; Mukhtarov, Furkat; Schang, Luis M; Kirschning, Andreas; Müller, Rolf; Guzman, Carlos A.; Kaderali, Lars; Randall, Glenn; Meuleman, Philip; Ploss, Alexander; Pietschmann, Thomas

    2015-01-01

    To explore mechanisms of hepatitis C virus (HCV) replication we screened a compound library including licensed drugs. Flunarizine, a diphenylmethylpiperazine used to treat migraine, inhibited HCV cell entry in vitro and in vivo in a genotype-dependent fashion. Analysis of mosaic viruses between susceptible and resistant strains revealed that E1 and E2 glycoproteins confer susceptibility to flunarizine. Time of addition experiments and single particle tracking of HCV demonstrated that flunarizine specifically prevents membrane fusion. Related phenothiazines and pimozide also inhibited HCV infection and preferentially targeted HCV genotype 2 viruses. However, phenothiazines and pimozide exhibited improved genotype coverage including the difficult to treat genotype 3. Flunarizine-resistant HCV carried mutations within the alleged fusion peptide and displayed cross-resistance to these compounds, indicating that these drugs have a common mode of action. Conclusion: These observations reveal novel details about HCV membrane fusion. Moreover, flunarizine and related compounds represent first-in-class HCV fusion inhibitors that merit consideration for repurposing as cost-effective component of HCV combination therapies. PMID:26248546

  13. Anti-soluble liver antigen (SLA) antibodies in chronic HCV infection.

    Science.gov (United States)

    Vitozzi, Susana; Lapierre, Pascal; Djilali-Saiah, Idriss; Marceau, Gabriel; Beland, Kathie; Alvarez, Fernando

    2004-05-01

    Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.

  14. NS3 protease polymorphisms and genetic barrier to drug resistance of distinct hepatitis C virus genotypes from worldwide treatment-naïve subjects.

    Science.gov (United States)

    Vidal, L L; Soares, M A; Santos, A F

    2016-11-01

    Hepatitis C virus (HCV) NS3 protease inhibitors have been primarily designed against genotype 1, the one with the lowest response to dual therapy. However, less evidence of their efficacy on non-1 genotypes is available, and any such information is mostly concentrated on genotypes 2-4. This study evaluated HCV protease resistance profiles in the major six HCV genotypes and identified genetic barrier (GB) profiles to each available protease inhibitor across HCV strains from different locations worldwide. We obtained 15 099 HCV sequences from treatment-naïve subjects retrieved at the Los Alamos HCV Sequence Database. The wild-type codons of different HCV genotypes were used to analyse the smallest number of nucleotide substitution steps required for changing that codon to the closest one associated with drug resistance. The 36L and 175L RAVs were found as genetic signatures of genotypes 2-5, while the 80K RAV was found in all genotype 5 sequences. Genotypes 4 and 6 showed a higher GB to RAV mutations conferring resistance to telaprevir, while genotypes 2-5 presented baseline resistance to that drug, carrying the 36L mutation. Genotype 4 had a higher GB to simeprevir resistance, requiring three substitutions to acquire the 155K mutation. Subtype 1b showed a higher GB than subtype 1a to resistance for most PIs, with RAVs at codons 36 and 155. Geographic disparities were also found in frequencies of certain RAVs in genotypes 2 and 3. Under a scenario of unprecedented evolution of anti-HCV direct-acting agents, the genetic composition of the circulating HCV sequences should be evaluated worldwide to choose the most appropriate/feasible therapeutic schemes with the highest genetic barriers to resistance. © 2016 John Wiley & Sons Ltd.

  15. An overview on hepatitis C virus genotypes and its control | Nouroz ...

    African Journals Online (AJOL)

    Hepatitis C virus (HCV) is a blood borne, circular and positive single stranded virus with high spread rates. With the passage of time the frequency of HCV is increasing in different parts of the world. HCV is a major cause, which may end in liver cirrhosis and hepatocellular carcinoma. HCV has six main genotypes with many ...

  16. An NS5A single optimized method to determine genotype, subtype and resistance profiles of Hepatitis C strains.

    Directory of Open Access Journals (Sweden)

    Elisabeth Andre-Garnier

    Full Text Available The objective was to develop a method of HCV genome sequencing that allowed simultaneous genotyping and NS5A inhibitor resistance profiling. In order to validate the use of a unique RT-PCR for genotypes 1-5, 142 plasma samples from patients infected with HCV were analysed. The NS4B-NS5A partial region was successfully amplified and sequenced in all samples. In parallel, partial NS3 sequences were analyzed obtained for genotyping. Phylogenetic analysis showed concordance of genotypes and subtypes with a bootstrap >95% for each type cluster. NS5A resistance mutations were analyzed using the Geno2pheno [hcv] v0.92 tool and compared to the list of known Resistant Associated Substitutions recently published. In conclusion, this tool allows determination of HCV genotypes, subtypes and identification of NS5A resistance mutations. This single method can be used to detect pre-existing resistance mutations in NS5A before treatment and to check the emergence of resistant viruses while undergoing treatment in major HCV genotypes (G1-5 in the EU and the US.

  17. Human Leukocyte Antigen Class II Alleles (DQB1 and DRB1 as Predictors for Response to Interferon Therapy in HCV Genotype 4

    Directory of Open Access Journals (Sweden)

    Olfat Shaker

    2013-01-01

    Full Text Available Human leukocyte antigens class II play an important role in immune response against HCV. We investigated whether HLA class II alleles influence susceptibility to HCV infection and response to interferon therapy. HLA-DRB1 and -DQB1 loci were genotyped using PCR-SSO Luminex technology. According to our regimen, 41 (66% of patients achieved sustained virological response to combined treatment of IFN and ribavirin. Frequencies of DQB1*0313 allele and DRB1*04-DRB1*11, DQB1*0204-DQB1*0313, DQB1*0309-DQB1*0313, and DQB1*0313-DQB1*0319 haplotypes were significantly more frequent in nonresponders than in responders. In contrast, DQB1*02, DQB1*06, DRB1*13, and DRB1*15 alleles were significantly more frequent in responders than in nonresponders. Similarly, DRB1*1301, DRB1*1361, and DRB1*1369 alleles and DRB1*1301-DRB1*1328, DRB1*1301-DRB1*1361, DRB1*1301-DRB1*1369, DRB1*1328-DRB1*1361, and DRB1*1328-DRB1*1369 haplotypes were significantly found only in responders. Some alleles and linkages showed significantly different distributions between patient and healthy groups. These alleles may be used as predictors for response to treatment or to susceptibility to HCV infection in the Egyptian population.

  18. The treatment of HCV in patients with haemoglobinopathy in Kurdistan Region, Iraq: a single centre experience.

    Science.gov (United States)

    Hussein, N R; Tunjel, I; Basharat, Z; Taha, A; Irving, W

    2016-06-01

    Various variables that might influence the rapid and sustained virological response to recombinant PEG-IFN-α-2a were explored in Iraqi HCV-infected patients with haemoglobinopathy. Forty-three patients were evaluated for the relationship between rapid virological response (RVR), IL-28B polymorphism, viral load, liver enzyme levels, blood group, ultrasound findings, or HCV genotype and the sustained virological response (SVR) achievement. The overall RVR was 55·81% while the overall SVR was 53·49%. SVR in patients that achieved RVR was 82·61% (P = 0·0004). A significant association was found between initial alanine transaminase levels and viral load with SVR achievement (P = 0·025) and (P = 0·004), respectively. Thirty-two (74%) out of 43 of our samples were host genotyped at the IL-28B locus as CC, a significant association was found between CC group and SVR achievement (P = 0·04). Of our samples, 23/43 (53%) were typed as HCV genotype 4, 10/43 (23%) as genotype 1, 9/43 (20·9%) as genotype 3 and 1/43 (2·3%) as genotype 2. A significant association was found between genotype 3 and SVR achievement (P = 0·006). Multivariate analysis showed that only RVR achievement independently associated with SVR in the Iraqi population (P = 0·00). These results can be used to classify the patients requiring the more expensive new direct-acting antiviral drugs.

  19. Hepatitis C virus infection among pregnant women in Slovenia: study on 31,849 samples obtained in four screening rounds during 1999, 2003, 2009 and 2013.

    Science.gov (United States)

    Kopilović, B; Poljak, M; Seme, K; Klavs, I

    2015-06-04

    The majority of people infected with hepatitis C virus (HCV) are unaware of their infection. Assessment of the prevalence of HCV infection in the general population and in key populations at increased risk is needed for evidence-based testing policies. Our objectives were to estimate the prevalence of antibodies to HCV (anti-HCV), the prevalence of HCV viraemia (HCV RNA), and to describe HCV genotype distribution among pregnant women in Slovenia. Unlinked anonymous testing was performed on residual sera obtained from 31,849 pregnant women for routine syphilis screening during 1999, 2003, 2009, and 2013. Anti-HCV reactive specimens were tested for HCV RNA and HCV genotypes were determined. Annual prevalence of anti-HCV ranged between 0.09% (95% confidence interval (CI): 0.03–0.18) in 2009 and 0.21% (95% CI: 0.12–0.34) in 2003 and HCV RNA positivity between 0.06% (95% CI: 0.02–0.14) in 2009 and 0.14% (95% CI: 0.07–0.25) in 2003. We observed no statistically significant differences in anti-HCV or HCV RNA prevalence between age groups (Slovenia could not be recommended.

  20. IL-10 and IL-28B gene variants as predictors of sustained response to peginterferon and ribavirin therapy in chronic HCV infection.

    Science.gov (United States)

    Sghaier, Ikram; Mouelhi, Leila; Rabia, Noor A; Ghazoueni, Ezzedine; Almawi, Wassim Y; Loueslati, Besma Yacoubi

    2017-04-05

    Interleukin-10 (IL-10) plays an important role in the immunity to hepatitis C virus (HCV). Insofar as IL-10 variants are associated with altered levels of IL-10, previous studies that examined the association of IL-10 polymorphisms with the susceptibility to and progression of chronic HCV, and response to anti-viral treatment were inconsistent. We investigated the association between common IL-10 variants in the intron and the promotor region with HCV and associated features. Study subjects comprised 120 patients infected with HCV-1b, and treated with Peg-IFN/RBV. Genotyping of six IL-10 promoter variants in the intron region (rs1878672, rs1554286, rs1518111) and promotor region (rs1800872, rs1800871, rs1800896) were done by real-time PCR. Compared to G/G, carriage of IL-10 rs1800896 (-1082A/G) A/A genotype was more frequent in patients with sustained virological response (SVR). The decline in viral load over the first 12weeks of treatment was more pronounced in rs1800896 A/A genotype carriers, compared to G/G genotype carriers, and was irrespective of the treatment dosage. Carriage of rs1800896 A/A genotype was positively associated with improvement in viral load decline, which was simultaneous, with and without carriage of the common favourable IL-28B variant. Carriage of both IL-10 rs1800896 G/G and IL-28B non-favourable genotype was associated with twice the risk of getting slow decline of viral load during treatment. Haploview analysis identified ACGCTA and CCGCTG haplotypes to be linked with excellent PegIFN/RBV cure rate, and complete HCV eradication. On the other hand, ACGCTG and CCGCTA haplotypes were associated with resistance to PegIFN/RBV treatment. IL-10 rs1800896 variant markedly influences the clinical outcome of HCV infection, and is a determinant of the response to HCV treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Influence of hepatitis C virus and IL28B genotypes on liver stiffness

    DEFF Research Database (Denmark)

    Lundbo, Lene Fogt; Clausen, Louise Nygaard; Weis, Nina

    2014-01-01

    OBJECTIVE: Liver fibrosis has been associated with hepatitis C virus (HCV) genotype and genetic variation near the interleukin 28B (IL28B) gene, but the relative contribution is unknown. We aimed to investigate the relation between HCV genotypes, IL28B and development of liver stiffness. PATIENTS...

  2. Transfusion Related Hepatitis C Virus (HCV) Infection in Sickle Cell ...

    African Journals Online (AJOL)

    Rev Olaleye

    ABSTRACT: This study aimed to determine retrospectively, the prevalence of hepatitis C virus infection in relation to a background history of blood transfusion; through anti HCV antibody screening test, amongst adult sickle cell disease patients. Anti HCV antibody was tested for in the serum of 92 consecutively selected ...

  3. Indeterminate RIBA results were associated with the absence of hepatitis C virus RNA (HCV-RNA) in blood donors.

    Science.gov (United States)

    Pereira, Felicidade Mota; Zarife, Maria Alice Sant'ana; Reis, Eliana Almeida Gomes; G Reis, Mitermayer

    2014-01-01

    Hepatitis C virus (HCV) infection is diagnosed by the presence of antibodies and is supplemented by confirmatory testing methods, such as recombinant immunoblot assay (RIBA) and HCV-RNA detection. This study aimed to evaluate the efficacy of RIBA testing to diagnose HCV infection in blood donors positive for anti-HCV antibodies. A total of 102 subjects positive for anti-HCV determined by enzyme-linked immunosorbent assay (ELISA) at the Hematology and Hemotherapy Foundation of Bahia (HEMOBA) were later assessed with new samples using the Abbott Architect anti-HCV test (Abbott Diagnostics, Wiesbaden, Germany), the RIBA III test (Chiron RIBA HCV 3.0 SIA, Chiron Corp., Emeryville, CA, USA), the polymerase chain reaction (PCR; COBAS® AMPLICOR HCV Roche Diagnostics Corp., Indianapolis, IN, USA) and line probe assay (LiPA - Siemens, Tarrytown, NY, USA) genotyping for HCV diagnosis. Of these new samples, 38.2% (39/102) were positive, 57.8% (59/102) were negative and 3.9% (4/102) were indeterminate for anti-HCV; HCV-RNA was detected in 22.5% (23/102) of the samples. RIBA results were positive in 58.1% (25/43), negative in 9.3% (4/43) and indeterminate in 32.6% (14/43) of the samples. The prevailing genotypes were 1 (78.3%, 18/23), 3 (17.4%, 4/23) and 2 (4.3%, 1/23). All 14 samples with indeterminate RIBA results had undetectable viral loads (detection limit ≤50 IU/mL). Of these samples, 71.4% (10/14) were reevaluated six months later. Eighty percent (8/10) of these samples remained indeterminate by RIBA, and 20% (2/10) were negative. In this study, individuals with indeterminate RIBA results had no detectable HCV-RNA.

  4. [Distribution of hepatitis C virus genotypes among patients with chronic hepatitis C infection in Akdeniz University Hospital, Antalya, Turkey: a five-year evaluation].

    Science.gov (United States)

    Sağlik, İmran; Mutlu, Derya; Öngut, Gözde; İnan, Dilara; Öğünç, Dilara; Can Sarinoğlu, Rabia; Özhak Baysan, Betil; Gültekin, Meral; Çolak, Dilek

    2014-07-01

    Hepatitis C virus (HCV) is one of the major causes of chronic hepatitis. It is important to know the genotypes of HCV in the decision of the HCV related chronic hepatitis therapy. The aim of this study was to evaluate the HCV genotypes determined at the Microbiology Laboratory of Akdeniz University Hospital, and to evaluate the changes in the distribution of the genotypes within the last five years. A total of 422 blood samples from HCV-RNA positive chronic hepatitis C patients (219 male, 203 female; age range: 8-79 yrs, mean age 46.3 ± 15.5 yrs) which were sent to our laboratory for genotyping between 2009-2013 period, were analyzed retrospectively. HCV-RNA extractions were performed in an automated system (EZ1 Virus Mini Kit v2.0, Qiagen, Germany), and a commercial reverse hybridization line probe-based assay (LIPA; GEN-C RT-PCR, Italy) was carried out for genotyping, For viral load determinations, a real-time PCR method (Cobas TaqMan HCV, Roche Diagnostics, Germany) was used. Demographic data of the patients were obtained from the hospital information systems and electronic patients' files. Out of the 422 patients, genotype 1b was detected in 63.3% (n= 267), genotype 1a in 14.7% (n= 62), genotype 3a in 11.1% (n= 47), genotype 2b in 0.9% (n= 4), genotype 4e in 0.2% (n= 1). The subtypes couldn't be determined for 5.4% (n= 23), 2.6% (n= 11) and 1.4% (n= 6) of the patients infected with genotype 1, 2 and 4, respectively. One (0.2%) patient, was coinfected with genotype 1 and 4. Of the patients, 40 were foreign-born (16 cases from Russia; 4 of each from Ukraine and Georgia; 3 of each from Turkmenistan, Kyrgyzstan, and Germany; one of each from Tajikistan, Azerbaijan, Uzbekistan, Chechnya, Moldova, Switzerland and Romania) and among these patients genotype 3a (19/40; 47.5%) was the most common genotype followed by genotype 1b (17/40; 42.5%). Median values of HCV viral load were 668.500 IU/ml (range: 2.000-9.630.000) in the whole group; while it was 732.000 IU

  5. Prevalence of α-thalassaemia genotypes in pregnant women in northern Thailand

    Science.gov (United States)

    Pharephan, Somphon; Sirivatanapa, Pannee; Makonkawkeyoon, Sanit; Tuntiwechapikul, Wirote; Makonkawkeyoon, Luksana

    2016-01-01

    Background & objectives: Alpha-thalassaemias are genetic disorders with high prevalence in northern Thailand. However, common genotypes and current data on the prevalence of α-thalassaemias have not been reported in this region. Therefore, the objective of the present study was to determine the prevalence of α-thalassaemia genotypes in pregnant women in northern Thailand. Methods: Genomic DNA was extracted from blood samples of pregnant women who came to Maharaj Nakorn Chiang Mai University Hospital during July 2009 to 2010. The common deletion and point mutation genotypes of α-thalassaemia were evaluated by gap- polymerase chain reaction (PCR) and PCR with restriction fragment length polymorphism (RFLP). Results: Genotypes of 638 pregnant women were: 409 samples (64.11%) being normal subjects (αα/αα) and 229 samples (35.89%) with α-thalassaemias. These 229 samples could be classified into deletional HbH disease (--SEA/-α3.7) for 18 samples (2.82%); heterozygous α0-thalassaemia --SEA type (--SEA/αα)) for 78 (12.23%); heterozygous α+-thalassaemia - α3.7 type (-α3.7/αα) for 99 (15.52%); homozygous α+-thalassaemia - α3.7 type (-α3.7/- α3.7) for five (0.78%); heterozygous α+-thalassaemia - α4.2 type (-α4.2/αα) for two (0.31%); and heterozygous HbCS (αCSα/αα) for 27 (4.23%) cases. Interpretation & conclusions: The prevalence of α-thalassaemias in pregnant women in northern Thailand was high. This finding supports the implementation of the prevention and control of this common genetic disorder by screening for α-thalassaemia genotypes. PMID:27241645

  6. Cervical HPV prevalence and genotype distribution in immunosuppressed Danish women

    DEFF Research Database (Denmark)

    Roensbo, Mette T; Blaakær, Jan; Skov, Karin

    2018-01-01

    INTRODUCTION: Women receiving immunosuppressive treatment due to organ transplantation are at increased risk of Human papilloma virus (HPV)-related diseases, including cervical neoplasia. This pilot study aimed to describe the cervical HPV prevalence and genotype distribution in immunosuppressed...... in 2014 had three cervical cytologies performed; one before and two after transplantation. The samples were examined for cytological abnormalities and tested for HPV using Cobas(®) HPV Test and CLART(®) HPV2 Test. RESULTS: Of 94 eligible cases we included 60 RTR and BMTR. The overall prevalence of high......-risk HPV was 15.0 (95% CI; 7.1-26.6) and the prevalence was higher among BMTR (29.4, CI; 10.3-56.0) than in RTR (9.3%, CI; 2.6-22.1) although this was not statistically significant (p=0.10). The distribution of high-risk HPV was broad with HPV 45 as the most common genotype (3.3%). The prevalences of high...

  7. Neutralizing antibodies in patients with chronic hepatitis C, genotype 1, against a panel of genotype 1 culture viruses: lack of correlation to treatment outcome.

    Directory of Open Access Journals (Sweden)

    Jannie Pedersen

    Full Text Available The correlation of neutralizing antibodies to treatment outcome in patients with chronic hepatitis C virus (HCV infection has not been established. The aim of this study was to determine whether neutralizing antibodies could be used as an outcome predictor in patients with chronic HCV, genotype 1, infection treated with pegylated interferon-α and ribavirin. Thirty-nine patients with chronic hepatitis C, genotype 1a or 1b, with either sustained virologic response (n = 23 or non-sustained virologic response (n = 16 were enrolled. Samples taken prior to treatment were tested for their ability to neutralize 6 different HCV genotype 1 cell culture recombinants (1a: H77/JFH1, TN/JFH1, DH6/JFH1; 1b: J4/JFH1, DH1/JFH1, DH5/JFH1. The results were expressed as the highest dilution yielding 50% neutralization (NAb50-titer. We observed no genotype or subtype specific differences in NAb50-titers between patients with chronic HCV infection with and without sustained virologic response when tested against any of the included culture viruses. However, NAb50-titers varied significantly with a mean reciprocal NAb50-titer of 800 (range: 100-6400 against DH6/JFH1 compared to a mean NAb50-titer of 50 (range: <50-400 against all other included isolates. Subsequent studies demonstrated that the efficient neutralization of DH6/JFH1 could be linked to engineered adaptive mutations in the envelope-2 protein. In analysis of envelope 1 and 2 sequences of HCV, recovered from a subset of patients, we observed no apparent link between relatedness of patient sequences with culture viruses used and the corresponding neutralization results. In conclusion, pre-treatment levels of neutralizing antibodies against HCV genotype 1 isolates could not predict treatment outcome in patients with chronic HCV infection. High neutralization susceptibility of DH6/JFH1 could be correlated with adaptive envelope mutations previously highlighted as important for neutralization. Our

  8. Indeterminate RIBA results were associated with the absence of hepatitis C virus RNA (HCV-RNA in blood donors

    Directory of Open Access Journals (Sweden)

    Felicidade Mota Pereira

    2014-01-01

    Full Text Available Introduction: Hepatitis C virus (HCV infection is diagnosed by the presence of antibodies and is supplemented by confirmatory testing methods, such as recombinant immunoblot assay (RIBA and HCV-RNA detection. This study aimed to evaluate the efficacy of RIBA testing to diagnose HCV infection in blood donors positive for anti-HCV antibodies. Methods: A total of 102 subjects positive for anti-HCV determined by enzyme-linked immunosorbent assay (ELISA at the Hematology and Hemotherapy Foundation of Bahia (HEMOBA were later assessed with new samples using the Abbott Architect anti-HCV test (Abbott Diagnostics, Wiesbaden, Germany, the RIBA III test (Chiron RIBA HCV 3.0 SIA, Chiron Corp., Emeryville, CA, USA, the polymerase chain reaction (PCR; COBAS® AMPLICOR HCV Roche Diagnostics Corp., Indianapolis, IN, USA and line probe assay (LiPA - Siemens, Tarrytown, NY, USA genotyping for HCV diagnosis. Results: Of these new samples, 38.2% (39/102 were positive, 57.8% (59/102 were negative and 3.9% (4/102 were indeterminate for anti-HCV; HCV-RNA was detected in 22.5% (23/102 of the samples. RIBA results were positive in 58.1% (25/43, negative in 9.3% (4/43 and indeterminate in 32.6% (14/43 of the samples. The prevailing genotypes were 1 (78.3%, 18/23, 3 (17.4%, 4/23 and 2 (4.3%, 1/23. All 14 samples with indeterminate RIBA results had undetectable viral loads (detection limit ≤50 IU/mL. Of these samples, 71.4% (10/14 were reevaluated six months later. Eighty percent (8/10 of these samples remained indeterminate by RIBA, and 20% (2/10 were negative. Conclusions: In this study, individuals with indeterminate RIBA results had no detectable HCV-RNA.

  9. New preclinical antimalarial drugs potently inhibit hepatitis C virus genotype 1b RNA replication.

    Directory of Open Access Journals (Sweden)

    Youki Ueda

    Full Text Available BACKGROUND: Persistent hepatitis C virus (HCV infection causes chronic liver diseases and is a global health problem. Although new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir has recently been started and is expected to achieve a sustained virologic response of more than 70% in HCV genotype 1 patients, there are several problems to be resolved, including skin rash/ageusia and advanced anemia. Thus a new type of anti-HCV drug is still needed. METHODOLOGY/PRINCIPAL FINDINGS: Recently developed HCV drug assay systems using HCV-RNA-replicating cells (e.g., HuH-7-derived OR6 and Li23-derived ORL8 were used to evaluate the anti-HCV activity of drug candidates. During the course of the evaluation of anti-HCV candidates, we unexpectedly found that two preclinical antimalarial drugs (N-89 and its derivative N-251 showed potent anti-HCV activities at tens of nanomolar concentrations irrespective of the cell lines and HCV strains of genotype 1b. We confirmed that replication of authentic HCV-RNA was inhibited by these drugs. Interestingly, however, this anti-HCV activity did not work for JFH-1 strain of genotype 2a. We demonstrated that HCV-RNA-replicating cells were cured by treatment with only N-89. A comparative time course assay using N-89 and interferon-α demonstrated that N-89-treated ORL8 cells had more rapid anti-HCV kinetics than did interferon-α-treated cells. This anti-HCV activity was largely canceled by vitamin E. In combination with interferon-α and/or ribavirin, N-89 or N-251 exhibited a synergistic inhibitory effect. CONCLUSIONS/SIGNIFICANCE: We found that the preclinical antimalarial drugs N-89 and N-251 exhibited very fast and potent anti-HCV activities using cell-based HCV-RNA-replication assay systems. N-89 and N-251 may be useful as a new type of anti-HCV reagents when used singly or in combination with interferon and/or ribavirin.

  10. The impact of HCV therapy in a high HIV-HCV prevalence population: A modeling study on people who inject drugs in Ho Chi Minh City, Vietnam.

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    Ruthie B Birger

    Full Text Available Human Immunodeficiency Virus (HIV and Hepatitis C Virus (HCV coinfection is a major global health problem especially among people who inject drugs (PWID, with significant clinical implications. Mathematical models have been used to great effect to shape HIV care, but few have been proposed for HIV/HCV.We constructed a deterministic compartmental ODE model that incorporated layers for HIV disease progression, HCV disease progression and PWID demography. Antiretroviral therapy (ART and Methadone Maintenance Therapy (MMT scale-ups were modeled as from 2016 and projected forward 10 years. HCV treatment roll-out was modeled beginning in 2026, after a variety of MMT scale-up scenarios, and projected forward 10 years.Our results indicate that scale-up of ART has a major impact on HIV though not on HCV burden. MMT scale-up has an impact on incidence of both infections. HCV treatment roll-out has a measurable impact on reductions of deaths, increasing multifold the mortality reductions afforded by just ART/MMT scale-ups.HCV treatment roll-out can have major and long-lasting effects on averting PWID deaths on top of those averted by ART/MMT scale-up. Efficient intervention scale-up of HCV alongside HIV interventions is critical in Vietnam.

  11. Evolution of simeprevir-resistant variants over time by ultra-deep sequencing in HCV genotype 1b.

    Science.gov (United States)

    Akuta, Norio; Suzuki, Fumitaka; Sezaki, Hitomi; Suzuki, Yoshiyuki; Hosaka, Tetsuya; Kobayashi, Masahiro; Kobayashi, Mariko; Saitoh, Satoshi; Ikeda, Kenji; Kumada, Hiromitsu

    2014-08-01

    Using ultra-deep sequencing technology, the present study was designed to investigate the evolution of simeprevir-resistant variants (amino acid substitutions of aa80, aa155, aa156, and aa168 positions in HCV NS3 region) over time. In Toranomon Hospital, 18 Japanese patients infected with HCV genotype 1b, received triple therapy of simeprevir/PEG-IFN/ribavirin (DRAGON or CONCERT study). Sustained virological response rate was 67%, and that was significantly higher in patients with IL28B rs8099917 TT than in those with non-TT. Six patients, who did not achieve sustained virological response, were tested for resistant variants by ultra-deep sequencing, at the baseline, at the time of re-elevation of viral loads, and at 96 weeks after the completion of treatment. Twelve of 18 resistant variants, detected at re-elevation of viral load, were de novo resistant variants. Ten of 12 de novo resistant variants become undetectable over time, and that five of seven resistant variants, detected at baseline, persisted over time. In one patient, variants of Q80R at baseline (0.3%) increased at 96-week after the cessation of treatment (10.2%), and de novo resistant variants of D168E (0.3%) also increased at 96-week after the cessation of treatment (9.7%). In conclusion, the present study indicates that the emergence of simeprevir-resistant variants after the start of treatment could not be predicted at baseline, and the majority of de novo resistant variants become undetectable over time. Further large-scale prospective studies should be performed to investigate the clinical utility in detecting simeprevir-resistant variants. © 2014 Wiley Periodicals, Inc.

  12. Prevalence of hepatitis C virus and human immunodeficiency virus in a group of patients newly diagnosed with active tuberculosis in Porto Alegre, Southern Brazil

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    Cintia Costi

    Full Text Available BACKGROUND Porto Alegre is the Brazilian state capital with second highest incidence of tuberculosis (TB and the highest proportion of people infected with human immunodeficiency virus (HIV among patients with TB. Hepatitis C virus (HCV infection increases the risk of anti-TB drug-induced hepatotoxicity, which may result in discontinuation of the therapy. OBJECTIVES The aim of this study was (i to estimate prevalence of HCV and HIV in a group of patients newly diagnosed with active TB in a public reference hospital in Porto Alegre and (ii to compare demographic, behavioural, and clinical characteristics of patients in relation to their HCV infection status. METHODS One hundred and thirty-eight patients with TB were tested for anti-HCV antibody, HCV RNA, and anti-HIV1/2 antibody markers. HCV RNA from real-time polymerase chain reaction (PCR-positive samples was submitted to reverse transcription and PCR amplification. The 5′ non-coding region of the HCV genome was sequenced, and genotypes of HCV isolates were determined. FINDINGS Anti-HCV antibody, HCV RNA, and anti-HIV antibodies were detected in 27 [20%; 95% confidence interval (CI, 13-26%], 17 (12%; 95% CI, 7-18%, and 34 (25%; 95% CI, 17-32% patients, respectively. HCV isolates belonged to genotypes 1 (n = 12 and 3 (n = 4. Some characteristics were significantly more frequent in patients infected with HCV. Among them, non-white individuals, alcoholics, users of illicit drugs, imprisoned individuals, and those with history of previous TB episode were more commonly infected with HCV (p < 0.05. MAIN CONCLUSIONS HCV screening, including detection of anti-HCV antibody and HCV RNA, will be important to improving the management of co-infected patients, given their increased risk of developing TB treatment-related hepatotoxicity.

  13. Prevalence of hepatitis C virus and human immunodeficiency virus in a group of patients newly diagnosed with active tuberculosis in Porto Alegre, Southern Brazil.

    Science.gov (United States)

    Costi, Cintia; Grandi, Tarciana; Halon, Maria Laura; Silva, Márcia Susana Nunes; Silva, Cláudia Maria Dornelles da; Gregianini, Tatiana Schäffer; Possuelo, Lia Gonçalves; Jarczewski, Carla Adriane; Niel, Christian; Rossetti, Maria Lucia Rosa

    2017-04-01

    Porto Alegre is the Brazilian state capital with second highest incidence of tuberculosis (TB) and the highest proportion of people infected with human immunodeficiency virus (HIV) among patients with TB. Hepatitis C virus (HCV) infection increases the risk of anti-TB drug-induced hepatotoxicity, which may result in discontinuation of the therapy. The aim of this study was (i) to estimate prevalence of HCV and HIV in a group of patients newly diagnosed with active TB in a public reference hospital in Porto Alegre and (ii) to compare demographic, behavioural, and clinical characteristics of patients in relation to their HCV infection status. One hundred and thirty-eight patients with TB were tested for anti-HCV antibody, HCV RNA, and anti-HIV1/2 antibody markers. HCV RNA from real-time polymerase chain reaction (PCR)-positive samples was submitted to reverse transcription and PCR amplification. The 5' non-coding region of the HCV genome was sequenced, and genotypes of HCV isolates were determined. Anti-HCV antibody, HCV RNA, and anti-HIV antibodies were detected in 27 [20%; 95% confidence interval (CI), 13-26%], 17 (12%; 95% CI, 7-18%), and 34 (25%; 95% CI, 17-32%) patients, respectively. HCV isolates belonged to genotypes 1 (n = 12) and 3 (n = 4). Some characteristics were significantly more frequent in patients infected with HCV. Among them, non-white individuals, alcoholics, users of illicit drugs, imprisoned individuals, and those with history of previous TB episode were more commonly infected with HCV (p < 0.05). HCV screening, including detection of anti-HCV antibody and HCV RNA, will be important to improving the management of co-infected patients, given their increased risk of developing TB treatment-related hepatotoxicity.

  14. Genetic Diversity and Selective Pressure in Hepatitis C Virus Genotypes 1-6: Significance for Direct-Acting Antiviral Treatment and Drug Resistance.

    Science.gov (United States)

    Cuypers, Lize; Li, Guangdi; Libin, Pieter; Piampongsant, Supinya; Vandamme, Anne-Mieke; Theys, Kristof

    2015-09-16

    Treatment with pan-genotypic direct-acting antivirals, targeting different viral proteins, is the best option for clearing hepatitis C virus (HCV) infection in chronically infected patients. However, the diversity of the HCV genome is a major obstacle for the development of antiviral drugs, vaccines, and genotyping assays. In this large-scale analysis, genome-wide diversity and selective pressure was mapped, focusing on positions important for treatment, drug resistance, and resistance testing. A dataset of 1415 full-genome sequences, including genotypes 1-6 from the Los Alamos database, was analyzed. In 44% of all full-genome positions, the consensus amino acid was different for at least one genotype. Focusing on positions sharing the same consensus amino acid in all genotypes revealed that only 15% was defined as pan-genotypic highly conserved (≥99% amino acid identity) and an additional 24% as pan-genotypic conserved (≥95%). Despite its large genetic diversity, across all genotypes, codon positions were rarely identified to be positively selected (0.23%-0.46%) and predominantly found to be under negative selective pressure, suggesting mainly neutral evolution. For NS3, NS5A, and NS5B, respectively, 40% (6/15), 33% (3/9), and 14% (2/14) of the resistance-related positions harbored as consensus the amino acid variant related to resistance, potentially impeding treatment. For example, the NS3 variant 80K, conferring resistance to simeprevir used for treatment of HCV1 infected patients, was present in 39.3% of the HCV1a strains and 0.25% of HCV1b strains. Both NS5A variants 28M and 30S, known to be associated with resistance to the pan-genotypic drug daclatasvir, were found in a significant proportion of HCV4 strains (10.7%). NS5B variant 556G, known to confer resistance to non-nucleoside inhibitor dasabuvir, was observed in 8.4% of the HCV1b strains. Given the large HCV genetic diversity, sequencing efforts for resistance testing purposes may need to be

  15. Prevalence of anti HCV infection in patients with beta-thalassemia in Isfahan-Iran

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    Behrooz Ataei

    2012-01-01

    Conclusions: Our findings revealed that blood transfusion was the main risk factors for HCV infection among beta-thalassemic patients. Therefore, more blood donor screening programs and effective screening techniques are needed to prevent transmission of HCV infection among beta-thalassemic patients.

  16. Comparative characteristics of immune answers indicators depending on the replicative activity and genotype of hepatitis c virus

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    Олеся Василівна Гололобова

    2015-08-01

    Full Text Available Aim. To analyze the character of changes and disorders of immune system with the help of complex study of indicators of cellular and humor section of immunity, cytokine status in patients with HCV-infection taking into account the replicative activity, genotype of virus and to formulate the possible causes of chronization.Methods. There were examined 155 patients with HCV-infection. An acute hepatitis C AHC was fixed in 23,9 %, chronic hepatitis C (CHC– in 76,1 %, 18–70 years old. Among examined patients with AHC and CHC prevailed men (67,6 and 72 % respectively. Diagnosis was set on the base of clinic and amnestic, epidemiologic, laboratory and instrumental data. Epidemiologic verification of diagnosis was realized by detection the specific serologic markers of HC (anti-HCV (sum, anti-HCV IgM and Ig G, anti-HCV core and anti-HCV NS-3, NS-4, NS-5 in blood serum using ELISA method. Molecular and genetic studies that included definition of replicative activity of HCV evaluated on the base of detection of RNA HCV in blood serum using the qualitative PCR method were carried out in 126 patients (31 with AHC and 95 with CHC. At the same time RNA of HCV was detected in peripheral blood in all (31 patients with AHC and in 74 (77,89 % patients with CHC. Using the method of restriction analysis we carried out the genetic typing of HCV in 90 patients with AHC and 60 with CHC. We carried out the comparative characteristics of the content of immunologic indicators in 45 (75 % patients with CHC with positive and 15 (25 % patients with negative results of PCR-study (polymerase chain reaction of HCV RNA in blood. For detection of regularities of changes of immune status depending on virus genotype there was carried out the comparative assessment of the content of immunologic indicators in patients with AHC and CHC with the most widespread genotypes of HVC– 1b and 3a. Immunologic studies included the definitions of the main subpopulations of lymphocytes

  17. Prevalence and Genotype Distribution of Pneumocystis jirovecii in Cuban Infants and Toddlers with Whooping Cough

    Science.gov (United States)

    Monroy-Vaca, Ernesto X.; de Armas, Yaxsier; Illnait-Zaragozí, María T.; Toraño, Gilda; Diaz, Raúl; Vega, Dania; Alvarez-Lam, Ileana; Calderón, Enrique J.

    2014-01-01

    This study describes the prevalence and genotype distribution of Pneumocystis jirovecii obtained from nasopharyngeal (NP) swabs from immunocompetent Cuban infants and toddlers with whooping cough (WC). A total of 163 NP swabs from 163 young Cuban children with WC who were admitted to the respiratory care units at two pediatric centers were studied. The prevalence of the organism was determined by a quantitative PCR (qPCR) assay targeting the P. jirovecii mitochondrial large subunit (mtLSU) rRNA gene. Genotypes were identified by direct sequencing of mtLSU ribosomal DNA (rDNA) and restriction fragment length polymorphism (RFLP) analysis of the dihydropteroate synthase (DHPS) gene amplicons. qPCR detected P. jirovecii DNA in 48/163 (29.4%) samples. mtLSU rDNA sequence analysis revealed the presence of three different genotypes in the population. Genotype 2 was most common (48%), followed in prevalence by genotypes 1 (23%) and 3 (19%); mixed-genotype infections were seen in 10% of the cases. RFLP analysis of DHPS PCR products revealed four genotypes, 18% of which were associated with resistance to sulfa drugs. Only contact with coughers (prevalence ratio [PR], 3.51 [95% confidence interval {CI}, 1.79 to 6.87]; P = 0.000) and exposure to tobacco smoke (PR, 1.82 [95% CI, 1.14 to 2.92]; P = 0.009) were statistically associated with being colonized by P. jirovecii. The prevalence of P. jirovecii in infants and toddlers with WC and the genotyping results provide evidence that this population represents a potential reservoir and transmission source of P. jirovecii. PMID:24131683

  18. Hepatitis C virus genotypes: A plausible association with viral loads

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    Salma Ghulam Nabi

    2013-01-01

    Full Text Available Background and Aim: The basic aim of this study was to find out the association of genotypes with host age, gender and viral load. Material and Methods: The present study was conducted at Social Security Hospital, Pakistan. This study included 320 patients with chronic hepatitis C virus (HCV infection who were referred to the hospital between November 2011 and July 2012. HCV viral detection and genotyping was performed and the association was seen between genotypes and host age, gender and viral load. Results : The analysis revealed the presence of genotypes 1 and 3 with further subtypes 1a, 1b, 3a, 3b and mixed genotypes 1b + 3a, 1b + 3b and 3a + 3b. Viral load quantification was carried out in all 151 HCV ribonucleic acid (RNA positive patients. The genotype 3a was observed in 124 (82.12% patients, 3b was found in 21 (13.91%, 1a was seen in 2 (1.32%, 1b in 1 (0.66%, mixed infection with 1b + 3a in 1 (0.66%, 1b + 3b in 1 (0.66% and 3a + 3b was also found in 1 (0.66% patient. Viral load quantification was carried out in all 151 HCV RNA positive patients and was compared between the various genotypes. The mean viral load in patients infected with genotype 1a was 2.75 × 10 6 , 1b 3.9 × 10 6 , 3a 2.65 × 10 6 , 3b 2.51 × 10 6 , 1b + 3a 3.4 × 106, 1b + 3b 2.7 × 106 and 3a + 3b 3.5 × 10 6 . An association between different types of genotypes and viral load was observed. Conclusion : Further studies should be carried out to determine the association of viral load with different genotypes so that sufficient data is available and can be used to determine the type and duration of therapy needed and predict disease outcome.

  19. An OPTIMIZE study retrospective analysis for management of telaprevir-treated hepatitis C virus (HCV)-infected patients by use of the Abbott RealTime HCV RNA assay.

    Science.gov (United States)

    Sarrazin, Christoph; Dierynck, Inge; Cloherty, Gavin; Ghys, Anne; Janssen, Katrien; Luo, Donghan; Witek, James; Buti, Maria; Picchio, Gaston; De Meyer, Sandra

    2015-04-01

    Protease inhibitor (PI)-based response-guided triple therapies for hepatitis C virus (HCV) infection are still widely used. Noncirrhotic treatment-naive and prior relapser patients receiving telaprevir-based treatment are eligible for shorter, 24-week total therapy if HCV RNA is undetectable at both weeks 4 and 12. In this study, the concordance in HCV RNA assessments between the Roche High Pure System/Cobas TaqMan and Abbott RealTime HCV RNA assays and the impacts of different HCV RNA cutoffs on treatment outcome were evaluated. A total of 2,629 samples from 663 HCV genotype 1 patients receiving telaprevir/pegylated interferon/ribavirin in OPTIMIZE were analyzed using the High Pure System and reanalyzed using Abbott RealTime (limits of detection, 15.1 IU/ml versus 8.3 IU/ml; limits of quantification, 25 IU/ml versus 12 IU/ml, respectively). Overall, good concordance was observed between the assays. Using undetectable HCV RNA at week 4, 34% of the patients would be eligible for shorter treatment duration with Abbott RealTime versus 72% with the High Pure System. However, using Abbott RealTime, a similar proportion (74%) would be eligible. Of the patients receiving 24-week total therapy, 87% achieved a sustained virologic response with undetectable HCV RNA by the High Pure System or Abbott RealTime; however, 92% of the patients with undetectable HCV RNA by Abbott RealTime achieved a sustained virologic response. Using undetectable HCV RNA as the cutoff, the more sensitive Abbott RealTime assay would identify fewer patients eligible for shorter treatment than the High Pure System. Our data confirm the Abbott RealTime assay, to determine eligibility for shortened PI-based HCV treatment. (The study was registered with ClinicalTrials.gov under registration no. NCT01241760.). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. Implementing and scaling up HCV treatment services for people who inject drugs and other high risk groups in Ukraine: An evaluation of programmatic and treatment outcomes.

    Science.gov (United States)

    Mazhnaya, Alyona; Meteliuk, Anna; Barnard, Tetiana; Zelenev, Alexei; Filippovych, Sergii; Altice, Frederick L

    2017-09-01

    HCV prevalence estimates among people who inject drugs (PWID) in Ukraine is high (60-90%), yet barriers to HCV treatment and care remain substantial including limited access to direct acting antiviral (DAA) medications. A feasibility scale-up project implemented HCV treatment in community-based settings to improve access to DAA treatment for key populations in this context. Using program-level data and verified medical records, we describe the development, implementation processes and outcomes for HCV treatment for PWID and other risks groups. Most participants (76%) received a combination of sofosbuvir, pegylated interferon, and ribavirin for 12 weeks. Treatment enrollment started in June 2015; the first two waves are reported. Data on demographics, HIV characteristics, HCV genotype and RNA levels, including sustained virologic response (SVR) were obtained from verified medical records. We used logistic regression to examine the independent correlates of achieving a SVR. The project was implemented in 19 healthcare institutions from 16 regions of Ukraine, mainly within AIDS specialty centers. Our analytical sample included 1126 participants who were mostly men (73%) and the majority were HIV co-infected (79%). Treatment retention was 97.7%; the proportions of participants who achieved SVR for the overall sample and for those with complete data (N=1029) were 86.2% (95% CI 84.08-88.19%) and 94.3% (95% CI 92.8-95.7%) respectively. The analysis of data restricted to only those with SVR data available showed that PWID who were currently injecting had comparable SVR rates (89.2%, 95% CI 81.5-94.5%) to PWID not injecting (94.4%, 95% CI 92.4-96.1), PWID on methadone (94.4%, 95%CI 92.4-96.1), and 'other' risk groups (95.2%, 95% CI 91.3-97.7). Independent factors associated with achieving a SVR were female sex (AOR: 3.44, 95% CI 1.45-8.14), HCV genotype 3 (AOR: 4.57, 95% CI 1.97-10.59) compared to genotype 1. SVR rates in PWID actively injecting did not differ significantly

  1. Ethnic and geographic variations in HPV prevalence and genotype distribution in north-western Yunnan, China.

    Science.gov (United States)

    Baloch, Zulqarnain; Yuan, Tao; Wang, Binghui; Tai, Wenlin; Feng, Yue; Liu, Yanqing; Li, Xiao; Feng, Yue; Liu, Li; Zhang, A-mei; Wu, Xiaomei; Xia, Xueshan

    2016-03-01

    The prevalence and genotype distribution of human papillomavirus (HPV) vary throughout the world. To assess the prevalence and genotype distribution of HPV among three ethnic groups in two geographic locations in north-western Yunnan, we recruited 522 women in Shangri-le (n = 255) and Lijiang (n = 267). PCR amplification of HPV DNA was performed on cervical cells from these women using two consensus primer systems (MY09/11 and GP5/6). Amplified-HPV DNA was genotyped using the HPV GenoArray test. Geographically, the HPV prevalence was significantly higher (P = 0.002) among Shangri-le women than among Lijiang women. Infections with high-risk (HR)-HPV and with multiple HPV genotypes were also significantly more common (P = 0.001) among women in Shangri-le than women in Lijiang. Additionally, the prevalence of overall, HR-HPV, and single genotype HPV infections was significantly higher (P = 0.001) among Tibetan women than among Naxi and Han women. HPV-16 and HPV-33 were significantly more frequent in Shangri-le women compared with Lijiang (P = 0.006) women. In addition, HPV-16 (9.81%) and HPV-33 (5.88%) were significantly more prevalent in Tibetan women than in Naxi and Han women. Here, for the first time, we highlight the significant variation in the prevalence and genotype distribution of HPV in various populations in the north-western region of Yunnan Province. © 2015 Wiley Periodicals, Inc.

  2. Human papilloma virus (HPV) genotypes prevalence in a region of South Italy (Apulia).

    Science.gov (United States)

    Coscia, Maria Franca; Monno, Rosa; Ballini, Andrea; Mirgaldi, Rosanna; Dipalma, Gianna; Pettini, Francesco; Cristallo, Vincenzo; Inchingolo, Francesco; Foti, Caterina; de Vito, Danila

    2015-01-01

    Since human papillomavirus (HPV) is the central casual factor in cervical cancer, understanding the epidemiology and geographical area distribution of the most prevalent HPV genotypes constitutes an important step towards development of strategies of prevention. The aim of this study was to investigate the prevalence of HPV infection and to determine HPV types distribution among 822 HPV positive women and some sexual male partners in Apulia (Italy). HPV DNA detection and genotyping was performed by nested-PCR for the L1 region and reverse line blot hybridization allowing the specific detection of 24 HPV genotyping both high risk (HR) and low risk (LR). The most prevalent HPV genotypes were HPV 16 (35%), HPV 31 (16%) HPV 6 (9%), HPV 58 and 66 (7%), followed by HPV 33 (6%), HPV 18 and 56 (4%), HPV 70 and 45 (3%), HPV 53 and 11 (2%). Currently 1.5% of tested specimens remained unclassified. Multiple infections with at last two different high- risk HPV genotypes were observed in 10% of specimens. This finding adds knowledge to HPV epidemiological investigation, and addresses further studies aimed to consider public health for identifying groups at risk for cervical cancer.

  3. Highly efficient full-length hepatitis C virus genotype 1 (strain TN) infectious culture system

    DEFF Research Database (Denmark)

    Li, Yi-Ping; Ramirez, Santseharay; Jensen, Sanne B

    2012-01-01

    Chronic infection with hepatitis C virus (HCV) is an important cause of end stage liver disease worldwide. In the United States, most HCV-related disease is associated with genotype 1 infection, which remains difficult to treat. Drug and vaccine development was hampered by inability to culture...... full-length TN infection dose-dependently. Given the unique importance of genotype 1 for pathogenesis, this infectious 1a culture system represents an important advance in HCV research. The approach used and the mutations identified might permit culture development for other HCV isolates, thus......) culture systems in Huh7.5 cells. Here, we developed a highly efficient genotype 1a (strain TN) full-length culture system. We initially found that the LSG substitutions conferred viability to an intergenotypic recombinant composed of TN 5' untranslated region (5'UTR)-NS5A and JFH1 NS5B-3'UTR; recovered...

  4. Prevalence of relevant NS5A resistance-associated substitutions to elbasvir in genotype 1a hepatitis C virus patients in Spain.

    Science.gov (United States)

    Palladino, Claudia; Esteban-Cartelle, Beatriz; Mate-Cano, Irene; Sánchez-Carrillo, Marta; Resino, Salvador; Briz, Verónica

    2018-05-01

    Resistance-associated substitutions (RASs) to the new HCV NS5A inhibitor elbasvir may limit its efficacy and lead to virological failure in HCV-GT1a-infected patients. There are no data outside clinical trials evaluating their prevalence and impact in grazoprevir/elbasvir in GT1a-infected patients in Spain. A multicentre cross-sectional study of 632 initial patients was conducted. In 13 of these patients, the sample could not be amplified or a consensus sequence by Sanger sequencing could not be performed. Ultimately, 617 HCV-G1a-infected individuals treated at 84 Spanish hospitals from the 17 autonomous communities plus the 2 autonomous cities of Spain were analysed. HCV population sequencing was used to identify RAS to elbasvir and the mutational pattern and drug sensitivity were confirmed by geno2pheno[HCV]. Viruses bearing RASs to elbasvir were present in 6.2% of HCV-G1a infected patients. The most common RASs were the Y93C/H/N and Q30E/H/R (2.4% and 2.3%, respectively). Only 3.4% of the identified RASs to elbasvir conferred reduced susceptibility to elbasvir by geno2pheno[HCV], which exclusively identified the positions Q30H/R (n=7) and Y93C/H/N (n=8) as single mutations and Q30H+Y93H (n=4) and Q30R+Y93H (n=2) as double mutations as the major RASs to elbasvir. A lower prevalence of RASs to elbasvir was observed in our HCV-G1a Spanish cohort than reported previously in clinical trials evaluating patients from the USA. This information may be essential to guide the implementation of grazoprevir/elbasvir in Spain and to manage G1a-infected patients. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  5. Low prevalence of hepatitis B and C among tuberculosis patients in Duhok Province, Kurdistan: Are HBsAg and anti-HCV prerequisite screening parameters in tuberculosis control program?

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    Muayad A Merza

    2016-01-01

    Full Text Available Objective/background: Viral hepatitis, particularly hepatitis B virus (HBV and hepatitis C virus (HCV, infections and tuberculosis (TB are a global public health concern. Co-infection with HBV or HCV among TB patients may potentiate the risk of hepatotoxicity induced by anti-TB drugs. Hence, the aim of this study was to identify the prevalence of HBV and HCV among TB patients included in the Duhok National Tuberculosis Program (NTP. Methods: The Duhok NTP Center is a specialized institution in Duhok City, Iraq, concerned with management and follow-up of TB patients. A cross-sectional study was conducted at the center between June 2015 and May 2016. All documented TB patients were analyzed on the basis of socio-demographic and other characteristics. Thereafter, all patients underwent screening for hepatitis B surface antigen (HBsAg, anti-HCV, and anti-HIV using enzyme-linked immunosorbent assay (ELISA. The results obtained were analyzed by entering the data in binary format into a Microsoft Excel spreadsheet. A p value of <.05 was considered to be statistically significant. Results: Two-hundred fourteen documented TB patients were recruited in this study, with 127 (59.3% males and 87 (40.7% females. The mean age of the patients was 40.34 years (±20.29. Of the total number of patients, four cases (1.8% were HBsAg-positive and one case (0.9% was positive for anti-HCV. The variables significantly associated with HBV were history of surgical dental procedure [odds ratio (OR, 0.04; 95% confidence interval (CI, −0.01 to 0.04; p = .03], and nationality (OR, 13.67; 95% CI, 0.46–210.85; p = .007. Conclusion: The prevalence of HBV and HCV co-infection among TB patients in this study was low. This may be explained by the low rate of blood transfusion among the patients, the very low prevalence of HIV infections in Kurdistan, the negative history of injection drug use, and adherence to universal infection-control measures, including vaccination for HBV

  6. Soroprevalência e genótipos do vírus da hepatite C em pacientes com lúpus eritematoso sistêmico (LES em Goiânia, Brasil Hepatitis C virus seroprevalence and genotypes in patients with systemic lupus erythematosus (SLE in Goiânia, Brazil

    Directory of Open Access Journals (Sweden)

    Vitalina de Souza Barbosa

    2005-08-01

    (HCV infection is a source of concern in rheumatology because of its extrahepatic manifestations. Many studies have reported association between HCV infection and rheumatological manifestations such as: musculoskeletal pain, essential mixed cryoglobulinemia, rheumatoid arthritis, Sjögren's syndrome, vasculitis, glomerulonephritis, Raynaud's phenomenon, polyarteritis nodosa, myositis, autoantibody and other connective tissue diseases. In previous studies developed in our region, prevalences of 0.9%, 1.4%, 1.8% and 2.0% were detected among pregnant women, blood donors, leprosy patients and health professionals, respectively. OBJECTIVE: to investigate the prevalence of hepatitis C virus infection among patients with systemic lupus erythematosus (SLE in Goiânia, Brazil. METHODS: 175 patients were interviewed and had blood samples tested for HCV antibodies (anti-HCV by a third generation enzyme linked immunosorbant assay (ELISA. RNA-HCV was detected by polymerase chain reaction (PCR with primers complementary the 5' non-coding region of the HCV genoma, in all anti-HCV positive serum samples and genotyped by a line probe assay. RESULTS: an overall HCV infection prevalence of 2.3% (4/175 was found. Genotyping of RNA-HCV positive samples revealed HCV type 1 in 3 (75% and type 3 in 1 (25% patient. Clinical course was favorable in all HCV positive patients, except one, who died due to renal insuficiency related to lupus nephritis. CONCLUSIONS: anti-HCV prevalence among patients with SLE was slitghly higher than the prevanlence observed in pregnant women, healthy blood donors and leprosy patients, and similar to health professionals.

  7. Infection of hepatitis C virus genotypes in hepatocellular carcinoma ...

    African Journals Online (AJOL)

    The aim of this retrospective study was to investigate the infection of hepatitis C virus (HCV) genotypes in hepatocellular carcinoma (HCC) patients from rural areas of Faisalabad region. Among 179 HCC subjects, men and women were 51 and 49%, respectively. All samples positive for HCV RNA by qualitative PCR were ...

  8. New hepatitis C virus genotype 1 subtype naturally harbouring resistance-associated mutations to NS5A inhibitors.

    Science.gov (United States)

    Ordeig, Laura; Garcia-Cehic, Damir; Gregori, Josep; Soria, Maria Eugenia; Nieto-Aponte, Leonardo; Perales, Celia; Llorens, Meritxell; Chen, Qian; Riveiro-Barciela, Mar; Buti, Maria; Esteban, Rafael; Esteban, Juan Ignacio; Rodriguez-Frias, Francisco; Quer, Josep

    2018-01-01

    Hepatitis C virus (HCV) is a highly divergent virus currently classified into seven major genotypes and 86 subtypes (ICTV, June 2017), which can have differing responses to therapy. Accurate genotyping/subtyping using high-resolution HCV subtyping enables confident subtype identification, identifies mixed infections and allows detection of new subtypes. During routine genotyping/subtyping, one sample from an Equatorial Guinea patient could not be classified into any of the subtypes. The complete genomic sequence was compared to reference sequences by phylogenetic and sliding window analysis. Resistance-associated substitutions (RASs) were assessed by deep sequencing. The unclassified HCV genome did not belong to any of the existing genotype 1 (G1) subtypes. Sliding window analysis along the complete genome ruled out recombination phenomena suggesting that it belongs to a new HCV G1 subtype. Two NS5A RASs (L31V+Y93H) were found to be naturally combined in the genome which could limit treatment possibilities in patients infected with this subtype.

  9. Human papilloma virus (HPV genotypes prevalence in a region of South Italy (Apulia

    Directory of Open Access Journals (Sweden)

    Maria Franca Coscia

    2015-09-01

    Full Text Available INTRODUCTION. Since human papillomavirus (HPV is the central casual factor in cervical cancer, understanding the epidemiology and geographical area distribution of the most prevalent HPV genotypes constitutes an important step towards development of strategies of prevention. AIM. The aim of this study was to investigate the prevalence of HPV infection and to determine HPV types distribution among 822 HPV positive women and some sexual male partners in Apulia (Italy. METHODS. HPV DNA detection and genotyping was performed by nested-PCR for the L1 region and reverse line blot hybridization allowing the specific detection of 24 HPV genotyping both high risk (HR and low risk (LR. RESULTS. The most prevalent HPV genotypes were HPV 16 (35%, HPV 31 (16% HPV 6 (9%, HPV 58 and 66 (7%, followed by HPV 33 (6%, HPV 18 and 56 (4%, HPV 70 and 45 (3%, HPV 53 and 11 (2%. Currently 1.5% of tested specimens remained unclassified. Multiple infections with at last two different high-risk HPV genotypes were observed in 10% of specimens. CONCLUSIONS. This finding adds knowledge to HPV epidemiological investigation, and addresses further studies aimed to consider public health for identifying groups at risk for cervical cancer.

  10. Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection

    Directory of Open Access Journals (Sweden)

    Pécheur Eve-Isabelle

    2006-07-01

    Full Text Available Abstract Arbidol (ARB is an antiviral compound that was originally proven effective for treatment of influenza and several other respiratory viral infections. The broad spectrum of ARB anti-viral activity led us to evaluate its effect on hepatitis C virus (HCV infection and replication in cell culture. Long-term ARB treatment of Huh7 cells chronically replicating a genomic length genotype 1b replicon resulted in sustained reduction of viral RNA and protein expression, and eventually cured HCV infected cells. Pre-treatment of human hepatoma Huh7.5.1 cells with 15 μM ARB for 24 to 48 hours inhibited acute infection with JFH-1 virus by up to 1000-fold. The inhibitory effect of ARB on HCV was not due to generalized cytotoxicity, nor to augmentation of IFN antiviral signaling pathways, but involved impaired virus-mediated membrane fusion. ARB's affinity for membranes may inhibit several aspects of the HCV lifecycle that are membrane-dependent.

  11. Frequency of anti-HCV antibodies in patients with lichen planus

    International Nuclear Information System (INIS)

    Mahboob, A.; Haroon, T.S.; Iqbal, Z.; Butt, A.K.

    2003-01-01

    Objective: To determine the frequency of anti-HCV antibodies, identify risk factors associated with HCV infection and to screen asymptomatic carries in patients with lichen planus. Subjects and Methods: A total of 184 clinically diagnosed cased of lichen (LP) were selected for the study. Blood samples of all the patients were tested for anti hepatitis C virus antibodies (anti-HCV-Ab). Polymerase chain reaction for hepatitis C virus was done in patients with positive anti-HCV-Ab. Trancutaneous liver biopsy was performed in 7 patients with positive HCV-RNA. The histopathological results were evaluated using validated Metavir and Knodell scoring systems. Results: Out of 184 LP patients, 43 (23.4%) were anti-HCV antibodies positive. Females were predominantly affected and male to female ratio was 1:5.1. Maximum positively for anti-HCV was observed in age group 31-40 years (39.53%) followed by 41-50 years (25.58%). Eighty-one percent patients had history of dental treatment and 63% had received multiple injections for various ailments. Forty percent patients had family history of jaundice while 26% had jaundice in the past. Ten out of 16 anti-HCV antibody positive patients, checked for HCV-RNA, had high levels of virus in blood. Transcutaneous liver biopsy done in 7 patients revealed underlying liver disease at various stages. Four patients treated with alpha-interferon and ribazole therapy for liver disease, showed marked improvement in their skin disease. Conclusion: A high prevalence of HCV infection was detected in patients with lichen planus. Patients with lichen planus should be screened for HCV carrier state. (author)

  12. Immune biomarker differences and changes comparing HCV mono-infected, HIV/HCV co-infected, and HCV spontaneously cleared patients.

    Directory of Open Access Journals (Sweden)

    Lauren E Kushner

    Full Text Available Immune biomarkers are implicated in HCV treatment response, fibrosis, and accelerated pathogenesis of comorbidities, though only D-dimer and C-reactive protein have been consistently studied. Few studies have evaluated HIV/HCV co-infection, and little longitudinal data exists describing a broader antiviral cytokine response.Fifty immune biomarkers were analyzed at baseline (BL and HCV end of treatment follow-up(FU time point using the Luminex 50-plex assay in plasma samples from 15 HCV-cleared, 24 HCV mono- and 49 HIV/HCV co-infected patients receiving antiretroviral treatment, who either did or did not receive pegylated-interferon/ribavirin HCV treatment. Biomarker levels were compared among spontaneous clearance patients, mono- and co-infected, untreated and HCV-treated, and sustained virologic responders (SVR and non-responders (NR at BL and FU using nonparametric analyses. A Bonferroni correction, adjusting for tests of 50 biomarkers, was used to reduce Type I error.Compared to HCV patients at BL, HIV/HCV patients had 22 significantly higher and 4 significantly lower biomarker levels, following correction for multiple testing. There were no significantly different BL levels when comparing SVR and NR in mono- or co-infected patients; however, FU levels changed considerably in co-infected patients, with seven becoming significantly higher and eight becoming significantly lower in SVR patients. Longitudinally between BL and FU, 13 markers significantly changed in co-infected SVR patients, while none significantly changed in co-infected NR patients. There were also no significant changes in longitudinal analyses of mono-infected patients achieving SVR or mono-infected and co-infected groups deferring treatment.Clear differences exist in pattern and quantity of plasma immune biomarkers among HCV mono-infected, HIV/HCV co-infected, and HCV-cleared patients; and with SVR in co-infected patients treated for HCV. Though >90% of patients were male and

  13. Impact of Immunogenetic IL28B Polymorphism on Natural Outcome of HCV Infection

    Directory of Open Access Journals (Sweden)

    Valli De Re

    2014-01-01

    Full Text Available With the aim of investigating whether interleukin 28B gene (IL28B rs1297860 polymorphism is associated with different hepatitis C (HCV infection statuses, we compared IL28B allelic distribution in an Italian case series of 1050 patients with chronic infection and different outcomes, 47 individuals who spontaneously cleared HCV, and 178 blood donors. Furthermore, we compared IL28B variants among 3882 Caucasian patients with chronic infection, 397 with spontaneous clearance, and 1366 blood donors reported in PubMed. Overall data confirmed a relation between IL28B C allele and HCV spontaneous clearance. Furthermore, we found that IL28B T allele had a weak relation with chronic HCV progression to hepatocellular carcinoma. Study findings are in accordance with the hepatocellular carcinogenic model where IL28B TT genotype, by promoting a persistent chronic hepatitis which leads to both hepatocyte injury and chronic inflammation, could facilitate HCC development. Conversely, patients with lymphoproliferative disorders had not any significantly different IL28B rs1297860 allelic distribution than those with chronic HCV, but, like all chronic HCV-related diseases, they showed a lower CC frequency than patients who spontaneously cleared HCV. Study results confirmed the model of persistent HCV infection as a risk factor for the pathogenesis of both liver and lymphoproliferative disorders.

  14. Current and future disease progression of the chronic HCV population in the United States.

    Science.gov (United States)

    Zalesak, Martin; Francis, Kevin; Gedeon, Alex; Gillis, John; Hvidsten, Kyle; Kidder, Phyllis; Li, Hong; Martyn, Derek; Orne, Leslie; Smith, Amanda; Kwong, Ann

    2013-01-01

    Chronic hepatitis C virus (HCV) infection can lead to advanced liver disease (AdvLD), including cirrhosis, decompensated cirrhosis, and liver cancer. The aim of this study was to determine recent historical rates of HCV patient progression to AdvLD and to project AdvLD prevalence through 2015. We first determined total 2008 US chronic HCV prevalence from the National Health and Nutrition Evaluation Surveys. Next, we examined disease progression and associated non-pharmacological costs of diagnosed chronic HCV-infected patients between 2007-2009 in the IMS LifeLink and CMS Medicare claims databases. A projection model was developed to estimate AdvLD population growth through 2015 in patients diagnosed and undiagnosed as of 2008, using the 2007-2009 progression rates to generate a "worst case" projection of the HCV-related AdvLD population (i.e., scenario where HCV treatment is the same in the forecasted period as it was before 2009). We found that the total diagnosed chronic HCV population grew from 983,000 to 1.19 million in 2007-2009, with patients born from 1945-1964 accounting for 75.0% of all patients, 83.7% of AdvLD patients, and 79.2% of costs in 2009, indicating that HCV is primarily a disease of the "baby boomer" population. Non-pharmacological costs grew from $7.22 billion to $8.63 billion, with the majority of growth derived from the 60,000 new patients that developed AdvLD in 2007-2009, 91.5% of whom were born between 1945 and 1964. The projection model estimated the total AdvLD population would grow from 195,000 in 2008 to 601,000 in 2015, with 73.5% of new AdvLD cases from patients undiagnosed as of 2008. AdvLD prevalence in patients diagnosed as of 2008 was projected to grow 6.5% annually to 303,000 patients in 2015. These findings suggest that strategies to diagnose and treat HCV-infected patients are urgently needed to increase the likelihood that progression is interrupted, particularly for patients born from 1945-1964.

  15. frequency and risk factors for chronic HCV infection: a community based study

    International Nuclear Information System (INIS)

    Tahir, M.; Mustafa, G.; Khan, M.B.

    2011-01-01

    It was a community based, cross-sectional study undertaken to assess the frequency of HCV infection and to find out the risk factors associated with its spread. Methods: Study was carried out from Oct 2004 to Mar 2005. One hundred and twenty five apparently healthy consecutive subjects not known to be infected with HBV or HCV, between the ages 13 and 60 years with equal sex distribution were selected from the population of the Village Mera Kalan near Rawalpindi. They were screened for Anti HCV antibodies using ELISA and interviewed in detail. Subjects found positive for Anti HCV Ab were tested for ALT (Alanine aminotransferase) levels and HCV RNA by PCR. Results: The frequency of HCV was found to be 53.6%. The most important risk factor associated with the transmission of HCV infection was unsafe injection therapy with contaminated equipment. Other risk factors include ear and nose piercing by unsterilized means in females and sharing of razors in males. Conclusion: The prevalence of HCV infection in our population is significantly higher than in the developed world. Public awareness programs should target the identified risk factors to prevent HCV transmission. (author)

  16. Prevalence of American Foulbrood and Paenibacillus Larvae Genotypes in Bulgaria

    OpenAIRE

    RUSENOVA, Nikolina; PARVANOV, Parvan

    2016-01-01

    This study aimed to analyse the prevalence of American foulbrood and Paenibacillus larvae genotypes in Bulgaria. For this purpose, data concerning American foulbrood outbreaks were used. Also, available data on the number of destroyed bee families covering a twenty-five-year period (1989 - 2013) was collected from the register of Bulgarian Food Safety Agency. In addition, Paenibacillus larvae genotypes in 15 apiaries were established by rep - PCR with BOXA1R and MBOREP1 primers. Results showe...

  17. The association of complex liver disorders with HBV genotypes prevalent in Pakistan

    Directory of Open Access Journals (Sweden)

    Qureshi Huma

    2007-11-01

    Full Text Available Abstract Background Genotyping of HBV is generally used for determining the epidemiological relationship between various virus strains and origin of infection mostly in research studies. The utility of genotyping for clinical applications is only beginning to gain importance. Whether HBV genotyping will constitute part of the clinical evaluation of Hepatitis B patients depends largely on the availability of the relevance of the evidence based information. Since Pakistan has a HBV genotype distribution which has been considered less virulent as investigated by earlier studies from south East Asian countries, a study on correlation between HBV genotypes and risk of progression to further complex hepatic infection was much needed Methods A total of 295 patients with HBsAg positive were selected from the Pakistan Medical Research Council's (PMRC out patient clinics. Two hundred and twenty six (77% were males, sixty nine (23% were females (M to F ratio 3.3:1. Results Out of 295 patients, 156 (53.2% had Acute(CAH, 71 (24.2% were HBV Carriers, 54 (18.4% had Chronic liver disease (CLD Hepatitis. 14 (4.7% were Cirrhosis and HCC patients. Genotype D was the most prevalent genotype in all categories of HBV patients, Acute (108, Chronic (39, and Carrier (53. Cirrhosis/HCC (7 were HBV/D positive. Genotype A was the second most prevalent with 28 (13% in acute cases, 12 (22.2% in chronics, 14 (19.7% in carriers and 5 (41.7 in Cirrhosis/HCC patients. Mixed genotype (A/D was found in 20 (12.8% of Acute patients, 3 (5.6% of Chronic and 4 (5.6% of carriers, none in case of severe liver conditions. Conclusion Mixed HBV genotypes A, D and A/D combination were present in all categories of patients except that no A/D combination was detected in severe conditions. Genotype D was the dominant genotype. However, genotype A was found to be more strongly associated with severe liver disease. Mixed genotype (A/D did not significantly appear to influence the clinical outcome.

  18. Retention in buprenorphine treatment is associated with improved HCV care outcomes.

    Science.gov (United States)

    Norton, B L; Beitin, A; Glenn, M; DeLuca, J; Litwin, A H; Cunningham, C O

    2017-04-01

    Persons who inject drugs, most of whom are opioid dependent, comprise the majority of the HCV infected in the United States. As the national opioid epidemic unfolds, increasing numbers of people are entering the medical system to access treatment for opioid use disorder, specifically with buprenorphine. Yet little is known about HCV care in patients accessing buprenorphine-based opioid treatment. We sought to determine the HCV prevalence, cascade of care, and the association between patient characteristics and completion of HCV cascade of care milestones for patients initiating buprenorphine treatment. We reviewed electronic health records of all patients who initiated buprenorphine treatment at a primary-care clinic in the Bronx, NY between January 2009 and January 2014. Of the 390 patients who initiated buprenorphine treatment, 123 were confirmed to have chronic HCV infection. The only patient characteristic associated with achieving HCV care milestones was retention in opioid treatment. Patients retained (vs. not retained) in buprenorphine treatment were more likely to be referred for HCV specialty care (63.1% vs. 34.0%, p<0.01), achieve an HCV-specific evaluation (40.8% vs. 21.3%, p<0.05), be offered HCV treatment (22.4% vs. 8.5%, p<0.05), and initiate HCV treatment (9.2% vs. 6.4%, p=0.6). Given the current opioid epidemic in the US and the growing number of people receiving buprenorphine treatment, there is an unprecedented opportunity to access and treat persons with HCV, reducing HCV transmission, morbidity and mortality. Retention in opioid treatment may improve linkage and retention in HCV care; innovative models of care that integrate opioid drug treatment with HCV treatment are essential. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. [Prevalence of positive markers for hepatitis B (HBV Ags) and hepatitis C (Anti-HCV) in health personnel at the Social Security Institute of Mexico State and Municipalities].

    Science.gov (United States)

    González-Huezo, M S; Sánchez-Hernández, E; Camacho, M C; Mejia-López, M D; Rebollo-Vargas, J

    2010-01-01

    The prevalence of serum markers of viral hepatitis in health-care workers seems to be similar to that described in the general population, even though this group would appear at increased risk because exposure to potentially infectious material. There is scarce information available in Mexico in this regard. To define the prevalence of serum markers for hepatitis C (anti-HCV antibodies) and hepatitis B (hepatitis B surface antigen, HBsAg) in health-care workers at the Instituto de Seguridad Social del Estado de Mexico y Municipios (ISSEMYM) and to establish the presence of viremia in subjects with positive serum markers. Health-care workers from ISSEMyM with unknown hepatitis serologic status participated voluntarily in this trial. They completed a written questionnaire detailing potential risk factors for viral hepatitis and provided a blood sample. A total of 374 health-care workers were included. Seven subjects (1.8%) were positive, 5 for anti-HCV antibodies (1.3%) and 2 for HBsAg (0.5%). None of these subjects had detectable serum HCV RNA or HBV DNA on further testing. The frequency of positive serum markers for viral hepatitis in this group of healthcare workers is similar to the estimated prevalence among the general population in Mexico. No case of active infection defined by positive viremia was encountered in this group of subjects.

  20. A Review of Hepatitis C Virus (HCV) and the Current Management ...

    African Journals Online (AJOL)

    Background: Chronic Hepatitis C virus (HCV) is the primary cause of cirrhosis, hepatocellular carcinoma (HCC), and end- stage liver disease. The addition of protease inhibitor with peginterferon alfa and ribavirin (triple therapy) for genotype 1 infected patients, are the current standard of care. Method: Data was sourced ...

  1. The epidiemiologic profile of HCV infected Hispanic patients from the southern area of Puerto Rico since 2005.

    Science.gov (United States)

    Colón-Ruiz, David; Rosado Carrión, Bárbara; Bredy, Rafael

    2012-01-01

    Seroprevalence studies in adults done in San Juan and Puerto Rico have showed 6.3% and 2.2% of the population respectively, are positive for antibodies to Hepatitis C Virus (anti-HCV). It is been suggested that Hispanics have a lower sustained virological response to current therapy. The epidemiologic profile, the response to treatment and the risk factors to the poor response to treatment of HCV patients have not been studied in the southern area of Puerto Rico. This is a cross-sectional analysis of data from 46 medical records from January 2005 to March 2011. We search for sociodemographic variables, comorbidities, the HCV genotype, the human immunodeficiency virus profile, history of alcoholism and the patients who were treated with peginterferon alpha 2b and ribavirin, and their response to treatment. Our HCV infected population is male predominant (63%), and the most common route of transmission were intravenous drug abuse (37%) and blood transfusions (33%). Only 37% reported alcoholism. The most common comorbidities found in our population were hypertension (35%), diabetes mellitus (20%), hypothyroidism (7%) and dyslipidemia (7%). Most common genotype found in our population was type 1 (61%). From the 46 patients, 10 patients were treated, being genotype 1 the most common. Overall, our population showed an epidemiological profile similar to other Hispanic groups in the literature, which should motivate us to continue exploring these associations, in an effort to improve the management of these patients.

  2. Prevalence of HIV, syphilis, HCV and their high risk behaviors among migrant workers in eastern China.

    Directory of Open Access Journals (Sweden)

    Xiaohong Pan

    Full Text Available OBJECTIVE: The goal of this study was to understand the knowledge about AIDS, identify the correlates and determine the prevalence of HIV infection, syphilis, HCV among migrant workers in Zhejiang, China. METHODS: A cross-sectional study using face-to-face anonymous questionnaire interviews was conducted and blood samples were collected for HIV, syphilis and Hepatitis C infection screening. RESULTS: 17,377 (92.8% of 18,730 migrant workers approached were interviewed. Among 17,377 participants, the HIV/AIDS knowledge rate was 66.2%. A total of 12,694 (73% of the participants reported having ever had sexual intercourse, with 30.1% of single participants reporting having had sexual intercourse. Among those respondents with sexual experiences, 7.5% admitted they had two or more sexual partners and 4.9% reported having had sex with casual (unpaid partners in the previous 12 months, whilst 3.7% had paid for sex. More than half of those who had paid for sex (59.4% had not used a condom every time in their sexual acts with the sex workers. Multiple logistic regression analysis indicated that high risk sexual behavior (defined as sex with a casual or commercial sex partner without using a condom consistently was associated with being divorced or widowed (P<0.05 for single; male gender; shorter duration of stay in Zhejiang; working in factory, market or domestic service (P<0.05 for odd job; having a province of origin inside Zhejiang; and drug use. The prevalence of HIV and HCV infections were 0.02% (95% CI: 0.01%-0.06% and 0.40% (95%CI: 0.31%-0.51%, respectively. The prevalence of syphilis among those who were sexually active was 0.55% (95% CI: 0.43%-0.70%. Risk factors for syphilis included shorter duration of stay in Zhejiang, ethnic minority status, being divorced or widowed and having had multiple sex partners. CONCLUSIONS: Much greater efforts are needed to promote safer sex, and programs for the control of syphilis need to be tailored for migrant

  3. Naturally occurring mutations associated with resistance to HCV NS5B polymerase and NS3 protease inhibitors in treatment-naïve patients with chronic hepatitis C.

    Science.gov (United States)

    Costantino, Angela; Spada, Enea; Equestre, Michele; Bruni, Roberto; Tritarelli, Elena; Coppola, Nicola; Sagnelli, Caterina; Sagnelli, Evangelista; Ciccaglione, Anna Rita

    2015-11-14

    The detection of baseline resistance mutations to new direct-acting antivirals (DAAs) in HCV chronically infected treatment-naïve patients could be important for their management and outcome prevision. In this study, we investigated the presence of mutations, which have been previously reported to be associated with resistance to DAAs in HCV polymerase (NS5B) and HCV protease (NS3) regions, in sera of treatment-naïve patients. HCV RNA from 152 naïve patients (84 % Italian and 16 % immigrants from various countries) infected with different HCV genotypes (21,1a; 21, 1b; 2, 2a; 60, 2c; 22, 3a; 25, 4d and 1, 4k) was evaluated for sequence analysis. Amplification and sequencing of fragments in the NS5B (nt 8256-8640) and NS3 (nt 3420-3960) regions of HCV genome were carried out for 152 and 28 patients, respectively. The polymorphism C316N/H in NS5B region, associated with resistance to sofosbuvir, was detected in 9 of the 21 (43 %) analysed sequences from genotype 1b-infected patients. Naturally occurring mutations V36L, and M175L in the NS3 protease region were observed in 100 % of patients infected with subtype 2c and 4. A relevant proportion of treatment naïve genotype 1b infected patients evaluated in this study harboured N316 polymorphism and might poorly respond to sofosbuvir treatment. As sofosbuvir has been approved for treatment of HCV chronic infection in USA and Europe including Italy, pre-treatment testing for N316 polymorphism on genotype 1b naïve patients should be considered for this drug.

  4. Vaccine-induced cross-genotype reactive neutralizing antibodies against hepatitis C virus

    DEFF Research Database (Denmark)

    Meunier, Jean-Christophe; Gottwein, Judith M; Houghton, Michael

    2011-01-01

    We detected cross-reactive neutralizing antibodies (NtAb) against hepatitis C virus (HCV) in chimpanzees vaccinated with HCV-1 (genotype 1a) recombinant E1/E2 envelope glycoproteins. Five vaccinated chimpanzees, protected following HCV-1 challenge, were initially studied using the heterologous H77......a, with limited reactivity against 2a and 3a. Our study provides encouragement for the development of a recombinant envelope-based vaccine against hepatitis C....

  5. Cyclophilin B stimulates RNA synthesis by the HCV RNA dependent RNA polymerase.

    Science.gov (United States)

    Heck, Julie A; Meng, Xiao; Frick, David N

    2009-04-01

    Cyclophilins are cellular peptidyl isomerases that have been implicated in regulating hepatitis C virus (HCV) replication. Cyclophilin B (CypB) is a target of cyclosporin A (CsA), an immunosuppressive drug recently shown to suppress HCV replication in cell culture. Watashi et al. recently demonstrated that CypB is important for efficient HCV replication, and proposed that it mediates the anti-HCV effects of CsA through an interaction with NS5B [Watashi K, Ishii N, Hijikata M, Inoue D, Murata T, Miyanari Y, et al. Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase. Mol Cell 2005;19:111-22]. We examined the effects of purified CypB proteins on the enzymatic activity of NS5B. Recombinant CypB purified from insect cells directly stimulated NS5B-catalyzed RNA synthesis. CypB increased RNA synthesis by NS5B derived from genotype 1a, 1b, and 2a HCV strains. Stimulation appears to arise from an increase in productive RNA binding. NS5B residue Pro540, a previously proposed target of CypB peptidyl-prolyl isomerase activity, is not required for stimulation of RNA synthesis.

  6. Hepatitis C Virus Antibodies in Dialysis Patients in Tunisia: A Single Center Study

    Directory of Open Access Journals (Sweden)

    Sassi F

    2000-01-01

    Full Text Available Fifty-eight patients on maintenance hemodialysis in a dialysis unit at Tunis, Tunisia were tested for anti-hepatitis C virus (anti-HCV antibodies by second generation ELISA test, and for HCV-RNA by nested reverse transcriptase polymerase chain reaction (RT-PCR of 5′ non-coding region. Specificity of the antibodies was confirmed by immunoblot test. HCV genotype was defined using INNO-LIPA test. Twenty-seven out of 58 patients (46.5% were reactive by ELISA. Transaminase levels were assessed over a six-month period and showed normal average values. Fourteen of the 27 anti-HCV positive patients (51% were positive by RT-PCR. Type 1b HCV genotype was the most prevalent, seen in all the dialysis patients and one patient in addition, was co-infected with genotype 4. There was a significant correlation between the duration on dialysis (over five years and the prevalence of anti-HCV-positive patients (P< 0.005 while no correlation existed between the number of blood transfusions and the presence of anti-HCV antibodies. The present study illustrates the high prevalence of HCV infection among Tunisian dialysis patients (51% and indicates that the spread may be nosocomial rather than transfusion-related.

  7. Structure-based drug design of novel peptidomimetic cellulose derivatives as HCV-NS3 protease inhibitors.

    Science.gov (United States)

    Saleh, Noha A; Elshemey, Wael M

    2017-10-15

    Hepatitis C Virus (HCV) represents a global health threat not only due to the large number of reported worldwide HCV infections, but also due to the absence of a reliable vaccine for its prevention. HCV NS3 protease is one of the most important targets for drug design aiming at the deactivation of HCV. In the present work, molecular docking simulations are carried out for suggested novel NS3 protease inhibitors applied to the Egyptian genotype 4. These inhibitors are modifications of dimer cellulose by adding a hexa-peptide to the cellulose at one of the positions 2, 3, 6, 2', 3' or 6'. Results show that the inhibitor compound with the hexa-peptide at position 6 shows significantly higher simulation docking score with HCV NS3 protease active site. This is supported by low total energy value of docking system, formation of two H-bonds with HCV NS3 protease active site residues, high binding affinity and increased stability in the interaction system. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. High prevalence of Human Parechovirus (HPeV) genotypes in the Amsterdam region and the identification of specific HPeV variants by direct genotyping of stool samples

    NARCIS (Netherlands)

    Benschop, K.; Thomas, X.; Serpenti, C.; Molenkamp, R.; Wolthers, K.

    2008-01-01

    Human Parechoviruses (HPeV) are widespread pathogens belonging to the Picornavirus family. Six genotypes are known which have predominantly been isolated from children. Data on prevalence of HPeV genotypes are generally based on cell culture, which may underestimate the prevalence of certain HPeV

  9. Identification of halosalicylamide derivatives as a novel class of allosteric inhibitors of HCV NS5B polymerase.

    Science.gov (United States)

    Liu, Yaya; Donner, Pamela L; Pratt, John K; Jiang, Wen W; Ng, Teresa; Gracias, Vijaya; Baumeister, Steve; Wiedeman, Paul E; Traphagen, Linda; Warrior, Usha; Maring, Clarence; Kati, Warren M; Djuric, Stevan W; Molla, Akhteruzzaman

    2008-06-01

    Halosalicylamide derivatives were identified from high-throughput screening as potent inhibitors of HCV NS5B polymerase. The subsequent structure and activity relationship revealed the absolute requirement of the salicylamide moiety for optimum activity. Methylation of either the hydroxyl group or the amide group of the salicylamide moiety abolished the activity while the substitutions on both phenyl rings are acceptable. The halosalicylamide derivatives were shown to be non-competitive with respect to elongation nucleotide and demonstrated broad genotype activity against genotype 1-3 HCV NS5B polymerases. Inhibitor competition studies indicated an additive binding mode to the initiation pocket that is occupied by the thiadiazine class of compounds and an additive binding mode to the elongation pocket that is occupied by diketoacids, but a mutually exclusive binding mode with respect to the allosteric thumb pocket that is occupied by the benzimidazole class of inhibitors. Therefore, halosalicylamides represent a novel class of allosteric inhibitors of HCV NS5B polymerase.

  10. Molecular beacon probes-base multiplex NASBA Real-time for detection of HIV-1 and HCV.

    Science.gov (United States)

    Mohammadi-Yeganeh, S; Paryan, M; Mirab Samiee, S; Kia, V; Rezvan, H

    2012-06-01

    Developed in 1991, nucleic acid sequence-based amplification (NASBA) has been introduced as a rapid molecular diagnostic technique, where it has been shown to give quicker results than PCR, and it can also be more sensitive. This paper describes the development of a molecular beacon-based multiplex NASBA assay for simultaneous detection of HIV-1 and HCV in plasma samples. A well-conserved region in the HIV-1 pol gene and 5'-NCR of HCV genome were used for primers and molecular beacon design. The performance features of HCV/HIV-1 multiplex NASBA assay including analytical sensitivity and specificity, clinical sensitivity and clinical specificity were evaluated. The analysis of scalar concentrations of the samples indicated that the limit of quantification of the assay was beacon probes detected all HCV genotypes and all major variants of HIV-1. This method may represent a relatively inexpensive isothermal method for detection of HIV-1/HCV co-infection in monitoring of patients.

  11. Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity.

    Directory of Open Access Journals (Sweden)

    Katja Pfafferott

    2011-02-01

    Full Text Available Cellular immune responses during acute Hepatitis C virus (HCV and HIV infection are a known correlate of infection outcome. Viral adaptation to these responses via mutation(s within CD8+ T-cell epitopes allows these viruses to subvert host immune control. This study examined HCV evolution in 21 HCV genotype 1-infected subjects to characterise the level of viral adaptation during acute and early HCV infection. Of the total mutations observed 25% were within described CD8+ T-cell epitopes or at viral adaptation sites. Most mutations were maintained into the chronic phase of HCV infection (75%. The lack of reversion of adaptations and high proportion of silent substitutions suggests that HCV has structural and functional limitations that constrain evolution. These results were compared to the pattern of viral evolution observed in 98 subjects during a similar phase in HIV infection from a previous study. In contrast to HCV, evolution during acute HIV infection is marked by high levels of amino acid change relative to silent substitutions, including a higher proportion of adaptations, likely reflecting strong and continued CD8+ T-cell pressure combined with greater plasticity of the virus. Understanding viral escape dynamics for these two viruses is important for effective T cell vaccine design.

  12. Is the use of IL28B genotype justified in the era of interferon-free treatments for hepatitis C?

    Science.gov (United States)

    Kanda, Tatsuo; Nakamoto, Shingo; Yokosuka, Osamu

    2015-01-01

    In 2009, several groups reported that interleukin-28B (IL28B) genotypes are associated with the response to peginterferon plus ribavirin therapy for chronic hepatitis C virus (HCV) infection in a genome-wide association study, although the mechanism of this association is not yet well understood. However, in recent years, tremendous progress has been made in the treatment of HCV infection. In Japan, some patients infected with HCV have the IL28B major genotype, which may indicate a favorable response to interferon-including regimens; however, certain patients within this group are also interferon-intolerant or ineligible. In Japan, interferon-free 24-wk regimens of asunaprevir and daclatasvir are now available for HCV genotype 1b-infected patients who are interferon-intolerant or ineligible or previous treatment null-responders. The treatment response to interferon-free regimens appears better, regardless of IL28B genotype. Maybe other interferon-free regimens will widely be available soon. In conclusion, although some HCV-infected individuals have IL28B favorable alleles, importance of IL28B will be reduced with availability of oral interferon free regimen. PMID:26279979

  13. Prevalence, risk factors and genotypes of hepatitis B infection among HIV-infected patients in the State of MS, Central Brazil

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    Solange Zacalusni Freitas

    2014-09-01

    Conclusion: This study demonstrates the low prevalence of HIV-HBV infection and also highlights the need for early vaccination against HBV as well as testing for HBV, HCV and HDV in all HIV-infected individuals.

  14. The management of HCV-infected pregnant women.

    Science.gov (United States)

    Valladares, Guillermo; Chacaltana, Alfonso; Sjogren, Maria H

    2010-01-01

    Hepatitis C is, at present, a worldwide health problem and is the most common cause of liver transplantation. Its prevalence in pregnant women is similar to that of the general population. In the absence of cirrhosis and portal hypertension, most HCV-infected pregnant women do not have obstetric complications. Screening of pregnant women that are asymptomatic and do not have risk factors is not cost effective. A high hepatitis C viral load reportedly increases vertical transmission and is higher in women who are coinfected with HIV or who are intravenous drug users. Prolonged rupture of the membrane for more than 6 h, amniocentesis, and perineal lacerations increase the potential risk of perinatal transmission. Although the hepatitis C virus can be transmitted intrapartum, prevention by caesarean delivery is not generally indicated. The HCV virus can be found in maternal milk; however, breast feeding is not contraindicated. In conclusion, there are no antiviral treatment recommendations for HCV-infected women during pregnancy, or guidelines for the prevention of vertical transmission.

  15. Therapeutic effectiveness of biosimilar standard interferon versus pegylated interferon for chronic hepatitis C genotypes 2 or 3

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    Aline Gonzalez Vigani

    Full Text Available BACKGROUND: Pegylated interferon (Peg-IFN and standard interferon (IFN play a significant role in the treatment of hepatitis C virus (HCV infection. Biosimilar standard IFN is widely available in Brazil for the treatment of HCV infection genotypes 2 or 3, but its efficacy compared to Peg-IFN is unknown. OBJECTIVE: To compare the sustained virological response (SVR rates following treatment with biosimilar standard IFN plus ribavirin (RBV versus Peg-IFN plus RBV in patients with HCV genotypes 2 or 3 infection. METHODS: A retrospective cohort study was conducted in patients with HCV genotypes 2 or 3 infection treated with biosimilar standard IFN plus RBV or with Peg-IFN plus RBV. SVR rates of the two treatments were compared. RESULTS: From January 2005 to December 2010, 172 patients with a mean age of 44 +/- 9.3 years were included. There were eight (4.7% patients with HCV genotype 2 infections. One hundred fourteen (66.3% were treated with biosimilar standard IFN plus RBV, whist 58 (33.7% patients were treated with Peg-IFN plus RBV. Between the two groups, there were no significant differences regarding age, gender, glucose level, platelet count, hepatic necroinflammatory grade, and hepatic fibrosis stage. Overall, 59.3% (102/172 patients had SVR. In patients treated with Peg-IFN plus RBV, 79.3% (46/58 had SVR compared to 49.1% (56/114 among those treated with biosimilar standard IFN plus RBV (p = 0.0001. CONCLUSION: In patients with HCV genotypes 2 or 3 infection, a higher SVR was observed in patients receiving Peg-IFN plus RBV related to patients treated with biosimilar standard IFN plus RBV.

  16. Report: Study is about the prevalence of the HCV disease and survival of HCV patients with associated factors in the population of district Multan.

    Science.gov (United States)

    Tabassum, Hina; Amin, Muhammad; Amanullah, Muhammad; Tabassum, Sana

    2015-09-01

    To find out the significant factors associated with HCV disease and evaluate the impact of these factors on the survival pattern of HCV patients in district Multan. The study was conducted in Nishter Hospital of Multan district from 1st January 2011 to 1st October 2012. To see a significant difference between the survival rates of patients with associated factors, non-parametric Cox- proportional hazard model with their graphical results were used. All the patients above 11 years old of both sexes were included in the study. All those who were surviving with HCV disease were studied with their associated factors such as age, family history (FH) barber/parlor services, blood group (BG) types weight loss (WL), Gender and drug use were collected from Nishter Hospital Multan. Results indicated that age, blood group types and gender are the most significant factors in the patients who are surviving with HCV disease. It was also observed that survival rate of female patients is high as compare to male patients.

  17. Prevalence of occult hepatitis C virus infection in the Iranian patients with human immunodeficiency virus infection.

    Science.gov (United States)

    Bokharaei-Salim, Farah; Keyvani, Hossein; Esghaei, Maryam; Zare-Karizi, Shohreh; Dermenaki-Farahani, Sahar-Sadat; Hesami-Zadeh, Khashayar; Fakhim, Shahin

    2016-11-01

    Occult hepatitis C virus (HCV) infection is a new form of chronic HCV infection described by the presence of the genomic HCV-RNA in liver biopsy and/or peripheral blood mononuclear cell (PBMC) samples, and undetectable levels or absence of HCV-RNA and in the absence or presence of anti HCV antibodies in the plasma specimens. The aim of the present study was to evaluate the occurrence of occult HCV infection (OCI) among Iranian subjects infected with human immunodeficiency virus (HIV) using RT-nested PCR. From March 2014 until April 2015, 109 Iranian patients with established HIV infection were enrolled in this cross-sectional study. After extraction of viral RNA from the plasma and PBMC samples, HCV-RNA status was examined by RT-nested PCR using primers from the 5'-NTR. HCV genotyping was conducted using RFLP analysis. For the confirmation of HCV genotyping by RFLP method, the PCR products were sequenced. Of the 109 patients, 50 were positive for antibodies against HCV. The HCV-RNA was detected in PBMC specimens in 6 (10.2%) out of the total 59 patients negative for anti-HCV Abs and undetectable plasma HCV-RNA and also from 4 (8.0%) out of the total 50 patients positive for anti-HCV Abs and undetectable plasma HCV-RNA. HCV genotyping analysis showed that 6 (60.0%) patients were infected with HCV subtype 3a, 3 (30.0%) were infected with HCV subtype 1a and 1 (10.0%) patient was infected with HCV subtype 1b. This study revealed the incidence of OCI (9.2%) in HIV-infected Iranian patients. Hence, designing prospective studies focusing on the detection of OCI in these patients would provide more information. J. Med. Virol. 88:1960-1966, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. HBV, HCV and HIV seroprevalence among blood donors in Istanbul, Turkey: how effective are the changes in the national blood transfusion policies?

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    Ali Acar

    Full Text Available The national blood transfusion policies have been changed significantly in recent years in Turkey. The purpose of this study was to determine the prevalence of HBV, HCV, and HIV in blood donors at the Red Crescent Center in Istanbul and to evaluate the effect of changes in the national blood transfusion policies on the prevalence of these infections. The screening results of 72695 blood donations at the Red Crescent Center in Istanbul between January and December 2007 were evaluated retrospectively. HBsAg, anti-HCV, and anti-HIV-1/2 were screened by microparticle enzyme immunoassay (MEIA method. Samples found to be positive for anti-HIV 1/2 and anti-HCV were confirmed by Inno-Lia HCV Ab III and Inno-Lia HIV I/II Score, respectively. The seropositivity rates for HBsAg, anti-HCV, and anti-HIV-1/2 were determined as 1.76%, 0.07%, and 0.008%, respectively. Compared to the previously published data from Red Crescent Centers in Turkey, it was found that HBV and HCV seroprevalances decreased and HIV seroprevalance increased in recent years. In conclusion, we believe that the drop in HBV and HCV prevalence rates are likely multifactorial and may have resulted from more diligent donor questioning upon screening, a higher level of public awareness on viral hepatitis as well as the expansion of HBV vaccination coverage in Turkey. Another factor to contribute to the decreased prevalence of HCV stems from the use of more sensitive confirmation testing on all reactive results, thereby eliminating a fair amount of false positive cases. Despite similar transmission routes, the increase in HIV prevalence in contrast to HBV and HCV may be linked to the increase in AIDS cases in Turkey in recent years.

  19. Rapid virological response of telaprevir and boceprevir in a Brazilian cohort of HCV genotype 1 patients: a multicenter longitudinal study

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    Borba HHL

    2017-01-01

    Full Text Available Helena HL Borba,1 Astrid Wiens,1 Laiza M Steimbach,1 Fernanda S Tonin,1 Maria LA Pedroso,2 Cláudia AP Ivantes,3 Fernando Fernandez-Llimos,4 Roberto Pontarolo1 1Pharmaceutical Sciences Postgraduate Research Program, Department of Pharmacy, 2Gastroenterology Service, Hospital de Clínicas, Federal University of Paraná, 3Guidance and Counseling Center, Curitiba City Hall, Curitiba, Paraná, Brazil; 4Department of Social Pharmacy, Faculty of Pharmacy, Research Institute for Medicines, University of Lisboa, Lisbon, Portugal Background: Chronic hepatitis C is a major public health issue, but there is a gap in the literature regarding the effectiveness and safety of direct-acting antiviral agents in the Brazilian population. The main aim of this study was to describe the effectiveness of boceprevir and telaprevir in patients treated at public health care institutions in Brazil.Materials and methods: A prospective longitudinal and multicenter study was conducted in five centers in the State of Paraná between September 2014 and June 2016. Data regarding effectiveness and safety were collected from medical records of patients treated with boceprevir or telaprevir. The effectiveness outcome comprised the rapid virological response (RVR. Multivariate analysis was performed to verify the influence of independent variables (ie, age, gender, baseline viral load on RVR achievement.Results: Data were collected from 117 patients with chronic hepatitis C virus (HCV genotype 1 infection. Fifteen patients received treatment with boceprevir and 102 received telaprevir. The mean age was 51.6 years, 64.1% were male, 44.4% were infected with HCV subtype 1a, 62.4% had a high baseline viral load (≥800,000 IU/mL and 33% were cirrhotic. Furthermore, 79.5% of patients achieved RVR (26.7% in the boceprevir group and 87.3% in the telaprevir group. Multivariate analysis demonstrated that the type of protease inhibitor (boceprevir or telaprevir and the baseline viral load

  20. Hepatitis C virus NS3 protease genotyping and drug concentration determination during triple therapy with telaprevir or boceprevir for chronic infection with genotype 1 viruses, southeastern France.

    Science.gov (United States)

    Aherfi, Sarah; Solas, Caroline; Motte, Anne; Moreau, Jacques; Borentain, Patrick; Mokhtari, Saadia; Botta-Fridlund, Danielle; Dhiver, Catherine; Portal, Isabelle; Ruiz, Jean-Marie; Ravaux, Isabelle; Bregigeon, Sylvie; Poizot-Martin, Isabelle; Stein, Andreas; Gérolami, René; Brouqui, Philippe; Tamalet, Catherine; Colson, Philippe

    2014-11-01

    Telaprevir and boceprevir, the two first hepatitis C virus (HCV) NS3 protease inhibitors (PIs), considerably increase rates of sustained virologic response in association with pegylated interferon and ribavirin in chronic HCV genotype 1 infections. The 30 first patients treated by telaprevir or boceprevir including anti-HCV therapies since 2011 in Marseille University hospitals, France, were monitored. HCV loads and plasmatic concentrations of telaprevir and boceprevir were determined on sequential blood samples. HCV NS3 protease gene population sequencing was performed at baseline of treatment and in case of treatment failure. Fifteen patients (including 7 co-infected with HIV) received telaprevir and the other 15 patients (including 4 co-infected with HIV) received boceprevir. At baseline, HCV NS3 protease from six patients harbored amino acid substitutions associated with PI-resistance. Treatment failure occurred at week 12 for 7 patients. Amino acid substitutions associated with PI-resistance were observed in six of these cases. HCV NS3 R155K and T54A/S mutants, all of genotype 1a, were found from four patients. Median (interquartile range) plasma concentrations were 3,092 ng/ml (2,320-3,525) for telaprevir and 486 ng/ml (265-619) for boceprevir. For HIV-HCV co-infected patients, median concentrations were 3,162 ng/ml (2,270-4,232) for telaprevir and 374 ng/ml (229-519) for boceprevir. Plasma drug concentration monitoring revealed undetectable concentrations for two patients at week 4, and probable non-adherence to therapy for another patient. These findings indicate that routine HCV NS3 protease sequencing and plasma PI concentration monitoring might be helpful to characterize cases of therapy failure, at a cost dramatically low compared to that of anti-HCV therapy. © 2014 Wiley Periodicals, Inc.

  1. Development of a New Structural Class of Broadly Acting HCV Non-Nucleoside Inhibitors Leading to the Discovery of MK-8876

    Energy Technology Data Exchange (ETDEWEB)

    McComas, Casey C.; Palani, Anandan; Chang, Wei; Holloway, M. Katharine; Lesburg, Charles A.; Li, Peng; Liverton, Nigel; Meinke, Peter T.; Olsen, David B.; Peng, Xuanjia; Soll, Richard M.; Ummat, Ajay; Wu, Jie; Wu, Jin; Zorn, Nicolas; Ludmerer, Steven W. (Merck); (WuXi App Tec)

    2017-07-25

    Studies directed at developing a broadly acting non-nucleoside inhibitor of HCV NS5B led to the discovery of a novel structural class of 5-aryl benzofurans that simultaneously interact with both the palm I and palm II binding regions. An initial candidate was potent in vitro against HCV GT1a and GT1b replicons, and induced multi-log reductions in HCV viral load when orally dosed to chronic GT1 infected chimpanzees. However, in vitro potency losses against clinically relevant GT1a variants prompted a further effort to develop compounds with sustained potency across a broader array of HCV genotypes and mutants. Ultimately, a biology and medicinal chemistry collaboration led to the discovery of the development candidate MK-8876. MK-8876 demonstrated a pan-genotypic potency profile and maintained potency against clinically relevant mutants. It demonstrated moderate bioavailability in rats and dogs, but showed low plasma clearance characteristics consistent with once-daily dosing. Herein we describe the efforts which led to the discovery of MK-8876, which advanced into Phase 1 monotherapy studies for evaluation and characterization as a component of an all-oral direct-acting drug regimen for the treatment of chronic HCV infection.

  2. HIV-, HCV-, and co-infections and associated risk factors among drug users in southwestern China: a township-level ecological study incorporating spatial regression.

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    Yi-Biao Zhou

    Full Text Available BACKGROUND: The human immunodeficiency virus (HIV and hepatitis C virus (HCV are major public health problems. Many studies have been performed to investigate the association between demographic and behavioral factors and HIV or HCV infection. However, some of the results of these studies have been in conflict. METHODOLOGY/PRINCIPAL FINDINGS: The data of all entrants in the 11 national methadone clinics in the Yi Autonomous Prefecture from March 2004 to December 2012 were collected from the national database. Several spatial regression models were used to analyze specific community characteristics associated with the prevalence of HIV and HCV infection at the township level. The study enrolled 6,417 adult patients. The prevalence of HIV infection, HCV infection and co-infection was 25.4%, 30.9%, and 11.0%, respectively. Prevalence exhibited stark geographical variations in the area studied. The four regression models showed Yi ethnicity to be associated with both the prevalence of HIV and of HIV/HCV co-infection. The male drug users in some northwestern counties had greater odds of being infected with HIV than female drug users, but the opposite was observed in some eastern counties. The 'being in drug rehabilitation variable was found to be positively associated with prevalence of HCV infection in some southern townships, however, it was found to be negatively associated with it in some northern townships. CONCLUSIONS/SIGNIFICANCE: The spatial modeling creates better representations of data such that public health interventions must focus on areas with high frequency of HIV/HCV to prevent further transmission of both HIV and HCV.

  3. High seroprevalence of HBV and HCV infection in HIV-infected adults in Kigali, Rwanda

    NARCIS (Netherlands)

    Rusine, John; Ondoa, Pascale; Asiimwe-Kateera, Brenda; Boer, Kimberly R.; Uwimana, Jean Marie; Mukabayire, Odette; Zaaijer, Hans; Mugabekazi, Julie; Reiss, Peter; van de Wijgert, Janneke H.

    2013-01-01

    Data on prevalence and incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in Rwanda are scarce. HBV status was assessed at baseline and Month 12, and anti-HCV antibodies at baseline, in a prospective cohort study of HIV-infected patients in Kigali, Rwanda: 104 men and 114

  4. Genetic variants in IL-6 and IL-10 genes and susceptibility to hepatocellular carcinoma in HCV infected patients.

    Science.gov (United States)

    Sghaier, Ikram; Mouelhi, Leila; Rabia, Noor A; Alsaleh, Bano R; Ghazoueni, Ezzedine; Almawi, Wassim Y; Loueslati, Besma Yacoubi

    2017-01-01

    Hepatitis C virus (HCV) infection is the major cause of hepatocellular carcinoma (HCC), a common primary liver malignancy, and the third leading cause of cancer-related death. The HCC risk increases with the severity of liver inflammation, and the clinical course of HCV infection depends on a balance between pro- and anti-inflammatory cytokines. The former includes interleukin (IL)-6, while the latter includes IL-10. However, the exact pathogenic mechanisms underlying IL-6 and IL-10 effects remain unclear. The present study evaluated 174 chronic HCV Tunisian patients. Polymorphisms of IL-6 (rs1880242, rs1474847, rs2069840, rs1800797, rs1800796, rs2069845, rs2069827, rs1474348, rs1800795), and IL-10 (rs1800896, rs1800871, rs1800872, rs1554286, rs1878672, rs1518111) were determined by real-time PCR. Notable differences between chronic HCV-infected patients and HCC patients were observed for the three IL-10 SNPs; rs1800871 (-819T/C), rs1800872 (-592A/C), and rs1878672. Carriage of IL-6 rs1800796 G/G genotype, IL-6 rs1474358 C-allele, and IL-6 rs1800797 A-allele was more frequent in chronic HCV-infected patients than in HCC patients. On the other hand, IL-6 rs1474358 GG genotype had a favourable factor for HCC establishment. IL-10 and IL-6 SNPs markedly influence the clinical outcomes of HCV infection. These SNPs could be used as biomarkers for early detection and molecular therapy for preventing HCC, and prognostic factors for predicting the clinical outcomes of HCC. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Hepatitis C genotypes /subtypes among chronic hepatitis patients in Saudi Arabia

    International Nuclear Information System (INIS)

    Shobokshi, Ossama A.; Serebour, Frank E.; Skakni, Leila L.

    2003-01-01

    To determine the molecular epidemiology of Hepatitis C virus (HCV) in K.S.A. 492 histological proven chronic HCV patients recruited from all regions of KSA,between November 1999 and March 2002 were genotyped and subtyped using amplified products of specific primers from the 5-UTR region in a reverse transcription polymerase chain reaction followed by a hybridization technique. 62% of Saudis were found to be genotype4. Other genotypes were 1(24.1%); 2(7.4%); 3(5.9%); 5(0.3%) add 10(0.3%).All regions showed similar distribution except except the Eastern region where subtype 2a/c emerged. 86% of Saudi chronic hepatitis C cases are due to genotypes 1 and 4.Since these are considered difficult to treat an aggressive approach to management using combination therapy of pegylated interferon plus ribavirin for 48 weeks should be considered for all cases of chronic hepatitis C until genotyping proves otherwise. (author)

  6. HCV Specific IL-21 Producing T Cells but Not IL-17A Producing T Cells Are Associated with HCV Viral Control in HIV/HCV Coinfection.

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    Sonya A MacParland

    Full Text Available Decreased hepatitis C virus (HCV clearance, faster cirrhosis progression and higher HCV RNA levels are associated with Human Immunodeficiency virus (HIV coinfection. The CD4+ T helper cytokines interleukin (IL-21 and IL-17A are associated with virus control and inflammation, respectively, both important in HCV and HIV disease progression. Here, we examined how antigen-specific production of these cytokines during HCV mono and HIV/HCV coinfection was associated with HCV virus control.We measured HCV-specific IL-21 and IL-17A production by transwell cytokine secretion assay in PBMCs from monoinfected and coinfected individuals. Viral control was determined by plasma HCV RNA levels.In acutely infected individuals, those able to establish transient/complete HCV viral control tended to have stronger HCV-specific IL-21-production than non-controllers. HCV-specific IL-21 production also correlated with HCV viral decline in acute infection. Significantly stronger HCV-specific IL-21 production was detected in HAART-treated coinfected individuals. HCV-specific IL-17A production was not associated with lower plasma HCV RNA levels in acute or chronic HCV infection and responses were stronger in HIV coinfection. HCV-specific IL-21/ IL-17A responses did not correlate with microbial translocation or fibrosis. Exogenous IL-21 treatment of HCV-specific CD8+ T cells from monoinfected individuals enhanced their function although CD8+ T cells from coinfected individuals were somewhat refractory to the effects of IL-21.These data show that HCV-specific IL-21 and IL-17A-producing T cells are induced in HIV/HCV coinfection. In early HIV/HCV coinfection, IL-21 may contribute to viral control, and may represent a novel tool to enhance acute HCV clearance in HIV/HCV coinfected individuals.

  7. Circulating Interferon-λ3, Responsiveness to HBV Vaccination, and HBV/HCV Infections in Haemodialysis Patients

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    Alicja E. Grzegorzewska

    2017-01-01

    Full Text Available The IFN-λ3 gene (IFNL3 plays a role in HCV clearance. We investigated circulating IFN-λ3 and IFNL3 SNPs in haemodialysis patients who differed in their response to HBV vaccination and their HBV/HCV infection status. In 201 patients, plasma IFN-λ3 was determined using ELISA. IFNL3 SNPs (rs12979860, rs8099917 were genotyped using HRM analysis. Differences in IFN-λ3 levels were shown between responders and nonresponders to HBV vaccination and between HBsAg-positive patients and those who developed anti-HBs after infection and became HBsAg negative. HBV vaccine responders without HCV resolution revealed lower IFN-λ3 than noninfected responders. HBsAg/HCV RNA-positive subjects showed lower IFN-λ3 than patients positive only for HCV RNA or subjects who resolved both infections. Circulating IFN-λ3 correlated positively with anti-HBs and negatively with positive HCV RNA testing in the adjusted regression analyses. HBV vaccine nonresponders, HBsAg-positive patients, and subjects with replicating HCV composed a group with unfavourable outcomes. Responders to HBV vaccination, subjects who became HBsAg negative, and those who cleared HCV were analysed as having favourable outcomes. The latter showed higher IFN-λ3 but did not differ in distribution of IFNL3 SNPs compared with subjects with unfavourable outcomes. Higher IFN-λ3 concentrations are associated with response to HBV vaccination, self-limited HBV infection, and HCV resolution.

  8. Prevalence of hepatitis C virus-resistant association substitutions to direct-acting antiviral agents in treatment-naïve hepatitis C genotype 1b-infected patients in western China

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    Li Z

    2017-10-01

    Full Text Available Zhao Li,* Zhi-wei Chen,* Hu Li, Hong Ren, Peng Hu Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China *These authors contributed equally to this work. Background: Direct-acting antivirals (DAAs against hepatitis C virus (HCV are potent and highly efficacious. However, resistance-associated substitutions (RASs relevant to DAAs can impair treatment effectiveness even at baseline. Moreover, the prevalence of baseline RASs in HCV genotype 1b-infected patients in western China is still unclear. Materials and methods: Direct sequencing of the HCV NS3, NS5A, and NS5B regions was performed in baseline serum samples of 70 DAAs treatment-naïve HCV 1b-infected patients in western China. The sequences were analyzed with MEGA version 5.05 software. Evolutionary patterns of RASs and amino-acid covariance patterns in the NS3, NS5A, and NS5B genes were analyzed by MEGA and Cytoscape (version 3.2.1, respectively.Results: The presence of at least one RAS in the NS3 region (C16S, T54S, Q80R/L, A87T, R117H, S122G, V132I, V170I was observed in 85.48% (53 of 62 of patients, RASs in the NS5A region (L28M, R30Q, Q54H, P58S/T, Q62H/R, Y93H were observed in 42.42% (28 of 66 of patients, and RASs in the NS5B region (N142S, A300T, C316N, A338V, S365A, L392I, M414L, I424V, A442T, V499A, S556G were observed in 100% (44 of 44 of patients. Evolutionary patterns of RASs and amino-acid covariance patterns for the NS3, NS5A, and NS5B genes are reported.Conclusion: The prevalence of RASs relevant to DAAs detected in the NS3, NS5A, and NS5B regions of HCV 1b from DAA treatment-naïve patients is high. Therefore, more attention should be paid to RASs associated with DAAs in the upcoming DAA-treatment era in China. Keywords: hepatitis C virus, unstructured proteins, resistance

  9. Nationwide prevalence of human papillomavirus infection and viral genotype distribution in 37 cities in China.

    Science.gov (United States)

    Wang, Rong; Guo, Xiao-Lei; Wisman, G Bea A; Schuuring, Ed; Wang, Wen-Feng; Zeng, Zheng-Yu; Zhu, Hong; Wu, Shang-Wei

    2015-07-04

    Type-specific high-risk HPV (hrHPV) infection is related to cervical carcinogenesis. The prevalence of hrHPV infection varies geographically, which might reflect the epidemiological characteristics of cervical cancer among different populations. To establish a foundation for HPV-based screening and vaccination programs in China, we investigated the most recent HPV prevalence and genotypic distributions in different female age groups and geographical regions in China. In 2012, a total of 120,772 liquid-based cytological samples from women enrolled for population- or employee-based cervical screening in 37 Chinese cities were obtained by the Laboratory of Molecular Infectious Diseases of Guangzhou KingMed. A total of 111,131 samples were tested by Hybrid Capture II and the other 9,641 were genotyped using the Tellgenplex™ HPV DNA Assay. The total positive rate for hrHPV was 21.07 %, which ranged from 18.42 % (Nanchang) to 31.94 % (Haikou) and varied by region. The regions of Nanchang, Changsha, Hangzhou, Chengdu, Fuzhou, Guangdong, and Guiyang could be considered the low prevalence regions. Age-specific prevalence showed a "two-peak" pattern, with the youngest age group (15-19 years) presenting the highest hrHPV infection rate (30.55 %), followed by a second peak for the 50-60-year-old group. Overall, the most prevalent genotypes were HPV16 (4.82 %) and HPV52 (4.52 %), followed by HPV58 (2.74 %). Two genotypes HPV6 (4.01 %) and HPV11 (2.29 %) were predominant in the low-risk HPV (lrHPV) type, while the mixed genotypes HPV16 + 52 and HPV52 + 58 were most common in women with multiple infections. This study shows that HPV infection in China has increased to the level of an "HPV-heavy-burden" zone in certain regions, with prevalence varying significantly among different ages and regions. Data from this study represent the most current survey of the nationwide prevalence of HPV infection in China, and can serve as valuable reference to guide nationwide cervical cancer

  10. Distinct Escape Pathway by Hepatitis C Virus Genotype 1a from a Dominant CD8+ T Cell Response by Selection of Altered Epitope Processing.

    Science.gov (United States)

    Walker, Andreas; Skibbe, Kathrin; Steinmann, Eike; Pfaender, Stephanie; Kuntzen, Thomas; Megger, Dominik A; Groten, Svenja; Sitek, Barbara; Lauer, Georg M; Kim, Arthur Y; Pietschmann, Thomas; Allen, Todd M; Timm, Joerg

    2016-01-01

    Antiviral CD8(+) T cells are a key component of the adaptive immune response against HCV, but their impact on viral control is influenced by preexisting viral variants in important target epitopes and the development of viral escape mutations. Immunodominant epitopes highly conserved across genotypes therefore are attractive for T cell based prophylactic vaccines. Here, we characterized the CD8(+) T cell response against the highly conserved HLA-B*51-restricted epitope IPFYGKAI1373-1380 located in the helicase domain of NS3 in people who inject drugs (PWID) exposed predominantly to HCV genotypes 1a and 3a. Despite this epitope being conserved in both genotypes, the corresponding CD8(+) T cell response was detected only in PWID infected with genotype 3a and HCV-RNA negative PWID, but not in PWID infected with genotype 1a. In genotype 3a, the detection of strong CD8(+) T cell responses was associated with epitope variants in the autologous virus consistent with immune escape. Analysis of viral sequences from multiple cohorts confirmed HLA-B*51-associated escape mutations inside the epitope in genotype 3a, but not in genotype 1a. Here, a distinct substitution in the N-terminal flanking region located 5 residues upstream of the epitope (S1368P; P = 0.00002) was selected in HLA-B*51-positive individuals. Functional assays revealed that the S1368P substitution impaired recognition of target cells presenting the endogenously processed epitope. The results highlight that, despite an epitope being highly conserved between two genotypes, there are major differences in the selected viral escape pathways and the corresponding T cell responses. HCV is able to evolutionary adapt to CD8(+) T cell immune pressure in multiple ways. Beyond selection of mutations inside targeted epitopes, this study demonstrates that HCV inhibits epitope processing by modification of the epitope flanking region under T cell immune pressure. Selection of a substitution five amino acids upstream of the

  11. Liver disease in adult transfusion-dependent beta-thalassaemic patients: investigating the role of iron overload and chronic HCV infection.

    Science.gov (United States)

    Kountouras, Dimitrios; Tsagarakis, Nikolaos J; Fatourou, Evangelia; Dalagiorgos, Efthimios; Chrysanthos, Nikolaos; Berdoussi, Helen; Vgontza, Niki; Karagiorga, Markissia; Lagiandreou, Athanasios; Kaligeros, Konstantinos; Voskaridou, Ersi; Roussou, Paraskevi; Diamanti-Kandarakis, Evanthia; Koskinas, John

    2013-03-01

    Iron overload and hepatitis-C virus (HCV) infection, have been implicated in the evolution of liver disease, in patients with transfusion-dependent beta-thalassaemia major (BTM). However, the impact of these factors in late stages of liver disease in adults with BTM, has not been extensively studied. To investigate serum indices of iron overload, HCV infection and liver disease, in a cohort of 211 adult Greek patients with BTM, in relation with the findings from liver biopsies. In this cross-sectional study, 211 patients with BTM were enrolled and studied, in relation with HCV infection, ferritin, transaminases, chelation treatment and antiviral treatment. Based on 109 patients biopsied, we correlated liver fibrosis, haemosiderosis and inflammation, with serum indices and HCV status Among all patients, 74.4% were anti-HCV positive (HCV+). Ferritin was positively correlated with transaminases and negatively correlated with age, while it was not significantly different among HCV+ and HCV- patients. Among the HCV+ patients, 55.4% reported antiviral treatment, while genotype 1 predominated. In a subfraction of 109 patients, in which liver biopsy was performed, 89% were HCV+ and 11% HCV-. Fibrosis was significantly correlated with age (P = 0.046), AST (P = 0.004), ALT (P = 0.044) and inflammation (P overload may be the critical determinant, since fibrosis is related to the minimal haemosiderosis, independently of HCV history. © 2012 John Wiley & Sons A/S.

  12. HCV Virus and Lymphoid Neoplasms

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    Yutaka Tsutsumi

    2011-01-01

    Full Text Available Hepatitis C virus (HCV is one of the viruses known to cause hepatic cancer. HCV is also believed to be involved in malignant lymphoma. In this paper, we investigated characteristics of malignant lymphoma cases that were anti-HCV antibody (HCV-Ab positive. We were able to perform pathological examinations on 13 out of 14 HCV-positive cases. Of these, lymphoid tissues of 10 stained positive for HCV-Ab. There was no significant correlation between the degree of HCV staining and the rate of recurrence or resistance to treatment. However, there did appear to be a consistent decrease in the amount of HCV-RNA between pre- and posttreatment among HCV-Ab-positive cases; that is, treatment-resistant cases that exhibited resistance from the first treatment and recurrent cases more frequently had a higher HCV level at treatment termination compared to the pretreatment level. This suggests that the HCV virus either accelerates oncogenesis by direct interaction with B cells or indirectly affects lymphoma prognosis.

  13. High false-negative rate of anti-HCV among Egyptian patients on regular hemodialysis.

    Science.gov (United States)

    El-Sherif, Assem; Elbahrawy, Ashraf; Aboelfotoh, Atef; Abdelkarim, Magdy; Saied Mohammad, Abdel-Gawad; Abdallah, Abdallah Mahmoud; Mostafa, Sadek; Elmestikawy, Amr; Elwassief, Ahmed; Salah, Mohamed; Abdelbaseer, Mohamed Ali; Abdelwahab, Kouka Saadeldin

    2012-07-01

    Routine serological testing for hepatitis C virus (HCV) infection among hemodialysis (HD) patients is currently recommended. A dilemma existed on the value of serology because some investigators reported a high rate of false-negative serologic testing. In this study, we aimed to detect the false-negative rate of anti-HCV among Egyptian HD patients. Seventy-eight HD patients, negative for anti-HCV, anti-HIV, and hepatitis B surface antigen, were tested for HCV RNA by reverse transcriptase polymerase chain reaction (RT-PCR). In the next step, the viral load was quantified by real-time PCR in RT-PCR-positive patients. Risk factors for HCV infection, as well as clinical and biochemical indicators of liver disease, were compared between false-negative and true-negative anti-HCV HD patients. The frequency of false-negative anti-HCV was 17.9%. Frequency of blood transfusion, duration of HD, dialysis at multiple centers, and diabetes mellitus were not identified as risk factors for HCV infection. The frequency of false-negative results had a linear relation to the prevalence of HCV infection in the HD units. Timely identification of HCV within dialysis units is needed in order to lower the risk of HCV spread within the HD units. The high false-negative rate of anti-HCV among HD patients in our study justifies testing of a large scale of patients for precious assessment of effectiveness of nucleic acid amplification technology testing in screening HD patient. © 2012 The Authors. Hemodialysis International © 2012 International Society for Hemodialysis.

  14. A new subtype of hepatitis C virus genotype 1: complete genome and phylogenetic relationships of an Equatorial Guinea isolate.

    Science.gov (United States)

    Bracho, Maria Alma; Carrillo-Cruz, Francy Yolima; Ortega, Enrique; Moya, Andrés; González-Candelas, Fernando

    2006-06-01

    Hepatitis C virus (HCV) is the leading cause of chronic liver disease and is associated with hepatocellular carcinoma. However, there have been few studies on the distribution and genetic diversity of HCV isolates in non-developed countries. Here, the complete genome sequence of an HCV genotype 1 isolate from Equatorial Guinea is reported, the first complete HCV-1 genome of African origin. Phylogenetic analysis revealed that this sequence always grouped with sequences of genotype 1, but did not group clearly with any subtype described so far. An analysis of partial NS5B gene sequences with additional sequences of African origin also failed to find close similarities between the new sequence and any previously known isolate. Genetic divergence of the coding region of this new sequence with respect to the recognized subtypes of HCV-1 ranged from 20 to 22%. It is proposed that this isolate is a representative of a new, distinct variant of HCV subtype 1.

  15. Four weeks of paritaprevir/ritonavir/ombitasvir plus dasabuvir encountering dengue fever resulted in sustained virological response in an HCV patient: A case report.

    Science.gov (United States)

    Huang, Chung-Feng; Jang, Tyng-Yuan; Lu, Po-Liang; Yu, Ming-Lung

    2016-11-01

    Direct antiviral agent (DAA) has been the standard of care for patients with hepatitis C virus (HCV) infection. Twelve weeks of paritaprevir/ritonavir/ombitasvir plus dasabuvir (PROD) with or without ribavirin has shown to have a sustained virological response at post-treatment 12 weeks (SVR12) rate of >90% in HCV genotype 1 (HCV-1) patients. We report a HCV-1b patient who received only 25 days of PROD treatment. The patient early terminated treatment due to dengue fever but eventually achieved SVR12. It may attribute to low baseline viral loads and extraordinarily rapid suppression of HCV after treatment day1. The finding may shed light for possible response-guided-therapy for so-called ultra-super-responders in the DAA era. Whether the dengue virus, the Flaviviridae family as with HCV, enhanced the HCV clearance remains unclear and needs further exploration.

  16. Prevalence and genotyping of HPV, by cervical brushing, in Irpinia area of Campania region

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    Pia Carmen Melillo

    2012-03-01

    Full Text Available Cervical cancer is due to persistent genital infection with Human Papillomavirus (HPV.The purpose of this study was to evaluate prevalence of HPV in Irpinia (Campania region, Italy, distribution of different viral genotypes, correlating cytological results and virological investigations. In the period 2006-2011, were made 1080 cervical samples of women aged 18-65 years for HPV identification and genotyping. Detection of the virus was performed by Multiplex-PCR System (Seegene,Arrow and typing with INNO-LiPA HPV Genotyping Extra test (Innogenetics. Out of the 1080 tested samples, 330 (30.6% samples were positive for HPV DNA. The most frequently occurring High Risk (HR-HPV genotype in single infections was HPV16 (16.6%, followed by HPV51 (10.7%, in multiple infections HPV16 (15.7% and 31 (14.6%. The prevalence of infection, correlated with age of patients studied, is greater in the group aged 26-30 years (42.5%. HR-HPV were detected in different percent in patients with Pap test scores: 22.5% in normal Pap smear (20% HPV16, 14.5% ASCUS (47.6% HPV16, 24% LSIL (20% HPV16, 79.3% HSIL (72.7% HPV16; 9.1% HPV18 detected only in this type of cellular alteration. The high prevalence of HR-HPV in patients with ASCUS or normal Pap test, suggesting the real advantage of HPV screening test, more sensitive in selecting the actual population at risk. Based on the findings of our epidemiological study, HR-HPV screening and HPV genotyping test should be strongly advised also to the vaccinated population for the high incidence of genotypes which are not included in vaccines (67%.

  17. Profile of paritaprevir/ritonavir/ombitasvir plus dasabuvir in the treatment of chronic hepatitis C virus genotype 1 infection

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    Smith MA

    2015-11-01

    Full Text Available Michael A Smith, Alice LimDepartment of Pharmacy Practice and Pharmacy Administration, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, USAAbstract: Over the last several years, many advances have been made in the treatment of chronic hepatitis C virus (HCV infection with the development of direct-acting antivirals. Paritaprevir/ritonavir/ombitasvir with dasabuvir (PrOD is a novel combination of a nonstructural (NS 3/4A protein inhibitor boosted by ritonavir, an NS5A protein inhibitor, and an NS5B nonnucleoside polymerase inhibitor. This review aims to discuss the pharmacology, efficacy, safety, drug interactions, and viral drug resistance of PrOD in the treatment of HCV genotype 1 infections. Phase I, II, and III human and animal studies that describe the pharmacology, pharmacokinetics, efficacy, and safety of PrOD for HCV were identified and included. Studies that evaluated patients without cirrhosis (n=2,249 and with cirrhosis (n=422 demonstrated that PrOD for 12 or 24 weeks was effective at achieving sustained virologic response rates (>90% in patients with genotype 1a or 1b HCV infection. Although indicated for the treatment of HCV genotype 1 infection, PrOD is also recommended for the treatment of HCV in patients coinfected with HIV. Additionally, promising data exist for the use of PrOD in liver-transplant recipients. The most common adverse drug events associated with PrOD included nausea, pruritus, insomnia, diarrhea, asthenia, dry skin, vomiting, and anemia. The high efficacy rates seen coupled with a favorable side effect profile seen with PrOD with or without ribavirin have led to its addition as a recommended treatment regimen for HCV genotype 1 infection.Keywords: direct-acting antiviral, interferon-free, ribavirin-free

  18. GB Virus C (GBV-C Infection in Hepatitis C Virus (HCV Seropositive Women with or at Risk for HIV Infection.

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    Jason T Blackard

    Full Text Available GB virus C (GBV-C may have a beneficial impact on HIV disease progression; however, the epidemiologic characteristics of this virus are not well characterized. Behavioral factors and gender may lead to differential rates of GBV-C infection; yet, studies have rarely addressed GBV-C infections in women or racial/ethnic minorities. Therefore, we evaluated GBV-C RNA prevalence and genotype distribution in a large prospective study of high-risk women in the US.438 hepatitis C virus (HCV seropositive women, including 306 HIV-infected and 132 HIV-uninfected women, from the HIV Epidemiologic Research Study were evaluated for GBV-C RNA. 347 (79.2% women were GBV-C RNA negative, while 91 (20.8% were GBV-C RNA positive. GBV-C positive women were younger than GBV-C negative women. Among 306 HIV-infected women, 70 (22.9% women were HIV/GBV-C co-infected. Among HIV-infected women, the only significant difference between GBV-negative and GBV-positive women was age (mean 38.4 vs. 35.1 years; p<0.001. Median baseline CD4 cell counts and plasma HIV RNA levels were similar. The GBV-C genotypes were 1 (n = 31; 44.3%, 2 (n = 36; 51.4%, and 3 (n = 3; 4.3%. The distribution of GBV-C genotypes in co-infected women differed significantly by race/ethnicity. However, median CD4 cell counts and log10 HIV RNA levels did not differ by GBV-C genotype. GBV-C incidence was 2.7% over a median follow-up of 2.9 (IQR: 1.5, 4.9 years, while GBV-C clearance was 35.7% over a median follow-up of 2.44 (1.4, 3.5 years. 4 women switched genotypes.Age, injection drug use, a history of sex for money or drugs, and number of recent male sex partners were associated with GBV-C infection among all women in this analysis. However, CD4 cell count and HIV viral load of HIV/HCV/GBV-C co-infected women were not different although race was associated with GBV-C genotype.

  19. EVALUATION OF EFFECTIVENESS OF ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C, CAUSED BY HCV GENOTYPE 6

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    D. A. Lioznov

    2017-01-01

    Full Text Available Objectives: Evaluating the effectiveness of 2 therapeutic schemes for chronic hepatitis C (genotype 6 which combined sofosbuvir and ribavirin, one of them also included pegylated interferon. Materials and methods: The study included 110 patients with chronic hepatitis C (genotype 6, who have undergone antiviral therapy (HTP in Hepatology Clinic inHo Chi Minh City,Vietnamfrom November 2015 to July 2016. 24 patients were treated by Pegylated interferon alfa-2a, ribavirin and sofosbuvir for 12 weeks, 86 patients – by sofosbuvir and ribavirin for 24 weeks. Non-interferon regimen was administered primarily to patients with contraindications to the use of interferon. To monitor the effectiveness of antiviral therapy, quantification of HCV RNA in serum was performed by PCR prior to treatment, at 4th, 12th or 24th week (depending on the observation group from the starting of treatment and at 12th, 24th week after completion of treatment. Results: All patients, who were treated with pegylated interferon, ribavirin and sofosbuvir, completed the full course of treatment and 100% of them are registered with sustained virological response at 12th and 24th week after the end of antiviral therapy (SVR-12 and SVR-24, respectively. In the group of patients, who treated with ribavirin and sofosbuvir, 97,7% of patients completed full course of treatment (SVR-12 was registered in 93% of patients, and SVR-24 – in 91,9% of patients. Of 75 patients without a history of HCC, SVR24 was registered in 74 people (98,7%, of 11 patients with HCC – in 5 patients (45,5%. SVR-24 was registered in 98% of patients with cirrhosis (F4 without HCC. Conclusion: The results can serve as a justification for the use of these schemes of antiviral therapy for special groups of patients and/or conditions when it is impossible to follow the latest recommendations, which will help to expand the access of patients to effective antiviral therapy for chronic hepatitis C.

  20. New insights into HCV replication in original cells from Aedes mosquitoes.

    Science.gov (United States)

    Fallecker, Catherine; Caporossi, Alban; Rechoum, Yassine; Garzoni, Frederic; Larrat, Sylvie; François, Olivier; Fender, Pascal; Morand, Patrice; Berger, Imre; Petit, Marie-Anne; Drouet, Emmanuel

    2017-08-22

    The existing literature about HCV association with, and replication in mosquitoes is extremely poor. To fill this gap, we performed cellular investigations aimed at exploring (i) the capacity of HCV E1E2 glycoproteins to bind on Aedes mosquito cells and (ii) the ability of HCV serum particles (HCVsp) to replicate in these cell lines. First, we used purified E1E2 expressing baculovirus-derived HCV pseudo particles (bacHCVpp) so we could investigate their association with mosquito cell lines from Aedes aegypti (Aag-2) and Aedes albopictus (C6/36). We initiated a series of infections of both mosquito cells (Ae aegypti and Ae albopictus) with the HCVsp (Lat strain - genotype 3) and we observed the evolution dynamics of viral populations within cells over the course of infection via next-generation sequencing (NGS) experiments. Our binding assays revealed bacHCVpp an association with the mosquito cells, at comparable levels obtained with human hepatocytes (HepaRG cells) used as a control. In our infection experiments, the HCV RNA (+) were detectable by RT-PCR in the cells between 21 and 28 days post-infection (p.i.). In human hepatocytes HepaRG and Ae aegypti insect cells, NGS experiments revealed an increase of global viral diversity with a selection for a quasi-species, suggesting a structuration of the population with elimination of deleterious mutations. The evolutionary pattern in Ae albopictus insect cells is different (stability of viral diversity and polymorphism). These results demonstrate for the first time that natural HCV could really replicate within Aedes mosquitoes, a discovery which may have major consequences for public health as well as in vaccine development.

  1. Resistance Analyses of HCV NS3/4A Protease and NS5B Polymerase from Clinical Studies of Deleobuvir and Faldaprevir.

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    Kristi L Berger

    Full Text Available The resistance profile of anti-hepatitis C virus (HCV agents used in combination is important to guide optimal treatment regimens. We evaluated baseline and treatment-emergent NS3/4A and NS5B amino-acid variants among HCV genotype (GT-1a and -1b-infected patients treated with faldaprevir (HCV protease inhibitor, deleobuvir (HCV polymerase non-nucleoside inhibitor, and ribavirin in multiple clinical studies.HCV NS3/4A and NS5B population sequencing (Sanger method was performed on all baseline plasma samples (n = 1425 NS3; n = 1556 NS5B and on post-baseline plasma samples from patients with virologic failure (n = 113 GT-1a; n = 221 GT-1b. Persistence and time to loss of resistance-associated variants (RAVs was estimated using Kaplan-Meier analysis.Faldaprevir RAVs (NS3 R155 and D168 and deleobuvir RAVs (NS5B 495 and 496 were rare (90%. Virologic relapse was associated with RAVs in both NS3 and NS5B (53% GT-1b; 52% GT-1b; some virologic relapses had NS3 RAVs only (47% GT-1a; 17% GT-1b. Median time to loss of GT-1b NS5B P495 RAVs post-treatment (5 months was less than that of GT-1b NS3 D168 (8.5 months and GT-1a R155 RAVs (11.5 months.Faldaprevir and deleobuvir RAVs are more prevalent among virologic failures than at baseline. Treatment response was not compromised by common NS3 polymorphisms; however, alanine at NS5B amino acid 499 at baseline (wild-type in GT-1a, polymorphism in GT-1b may reduce response to this deleobuvir-based regimen.

  2. Development of a TaqMan assay for the six major genotypes of hepatitis C virus: Comparison with commercial assays

    DEFF Research Database (Denmark)

    Engle, Ronald E; Russell, Rodney S; Purcell, Robert H

    2008-01-01

    A quantitative real-time PCR assay was developed that detects genomic RNA from reference strains representing the six major genotypes of hepatitis C virus (HCV) with equal sensitivity and accurately measured HCV RNA in JFH1 HCV-infected Huh7.5 cells. The method is indirectly calibrated to the first...

  3. High Prevalence and Genotypic Diversity of the Human Papillomavirus in Amazonian Women, Brazil

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    Danielle Albuquerque Pires Rocha

    2013-01-01

    Full Text Available The aim of this study was to determine the prevalence of human papillomavirus (HPV in a women population living within the state of Amazonas, Brazil, and to determine the viral genotypes found. The study included 361 sexually active women over 18 years of age. We performed the Pap test and the molecular diagnosis for HPV DNA using polymerase chain reaction (PCR. The amplicons obtained were sequenced in automatic sequencer for genotyping. The presence of HPV DNA was found in 29.1% (105 of the women. Only 321 women presented satisfactory slides for cytological diagnosis, 97.9% (314 had normal cytology (negative for cancer, and 2.1% (7 had abnormal cytology (4 ASCUS, 1 LSIL, and 2 HSIL. The types more frequently found were HPV 16 (58.1% and HPV 58 (20.0%. Additionally, we found more 13 types of HPV. Compared with previous studies in Brazil, our data confirmed a high prevalence and genotypic diversity of HPV in Brazilian women.

  4. Detection of hepatitis C virus (HCV among health care providers in an Egyptian university hospital: different diagnostic modalities

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    El-Sokkary RH

    2017-10-01

    Full Text Available Rehab H El-Sokkary,1 Rehab M Elsaid Tash,1 Takwa E Meawed,1 Omnia S El Seifi,2 Eman M Mortada2 1Medical Microbiology and Immunology Department, 2Community, Environmental and Occupational Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt Background: Hepatitis C virus (HCV infection has received much attention and is placed at the core of the infection control agenda. It is considered as a major public health problem in Egypt, where the highest prevalence of HCV exists. The great risk of exposure to infection of health care providers (HCPs has highlighted the urgent need for implementing an infection control program. Objective: The purpose of this study was to detect the prevalence of HCV infection among HCPs in Zagazig University Hospitals and to assess the performance of different diagnostic modalities.Methodology: Blood, polymerase chain reaction (PCR, enzyme-linked immunosorbent assay (ELISA, and saliva tests were performed in enrolled HCPs.Results: This study compared HCV diagnosis Hepanostika HCV Ultra ELISA as a screening test and PCR as gold standard test, which resulted in 40.6% positive results by ELISA compared to 34.8% by PCR (p<0.0001, while OraQuick HCV rapid antibody compared to PCR shows that 37.7% of the participants were positive by OraQuick HCV rapid antibody test. Application of standard precautions while dealing with blood has negative significant correlation with HCV infection (rs=–0.265, p=0.03.Conclusion: HCPs at Zagazig University Hospitals are at high risk for HCV infection. Lack of compliance and awareness of prevention and control of the infection are associated cofactors. Serum HCV-Ab detection by Hepanostika HCV Ultra ELISA and OraQuick HCV rapid antibody test are sensitive and specific serologic assays for diagnosis with correspondent results to that obtained by quantitative real-time PCR. Keywords: HCV, ROC curve, OraQuick HCV, infection control

  5. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes

    DEFF Research Database (Denmark)

    Smith, Donald B; Bukh, Jens; Kuiken, Carla

    2014-01-01

    additional complete coding region sequences of unassigned subtype. The study additionally describes the development of a Web resource hosted by the International Committee for Taxonomy of Viruses (ICTV) that maintains and regularly updates tables of reference isolates, accession numbers, and annotated......UNLABELLED: The 2005 consensus proposal for the classification of hepatitis C virus (HCV) presented an agreed and uniform nomenclature for HCV variants and the criteria for their assignment into genotypes and subtypes. Since its publication, the available dataset of HCV sequences has vastly...

  6. Evidence of intratypic recombination in natural populations of hepatitis C virus

    International Nuclear Information System (INIS)

    Colina, R.; Garcia-Aguirre, L.; Cristina, J.; Casane, D.; Vasquez, S.; Khan, Baldip

    2004-01-01

    Hepatitis C virus (HCV) has high genomic variability and, since its discovery, at least six different types and an increasing number of subtypes have been reported. Genotype 1 is the most prevalent genotype found in South America. In the present study, three different genomic regions (5 UTR, core and NS5B) of four HCV strains isolated from Peruvian patients were sequenced in order to investigate the congruence of HCV genotyping for these three genomic regions. Phylogenetic analysis using 5 UTR-core sequences found strain PE22 to be related to subtype 1a. To test the possibility of genetic recombination, phylogenetic studies were carried out, revealing that a crossover event had taken place in the NS5B protein. We discuss the consequences of this observation on HCV genotype classification, laboratory diagnosis and treatment of HCV infection

  7. Prevalence, knowledge and awareness of hepatitis C among residents of three union councils in Mansehra

    International Nuclear Information System (INIS)

    Jamil, M.S.

    2010-01-01

    Pakistan is home to approximately 10 million HCV infected people. HCV prevalence is expected to be higher in the earthquake affected area of Tehsil Oghi. The aim of this study was to estimate HCV prevalence in three Union Councils of Tehsil Oghi, i.e., Oghi, Shamdhara and Kathai, and to assess HCV knowledge and awareness in the population. Methods: This is an observational study carried out during June 2010. Blood samples of 648 participants were analysed for the presence of anti HCV antibodies using Immuno-chromatographic method and a knowledge and awareness questionnaire was administered to the participants. Results: 394 (61%) participants were females, while 254 (39% ) were males. The overall prevalence of HCV in the study area was recorded as 67 (10.3%). Prevalence among male participants was 30 (11.8%), whereas, that among female participants was 37 (9.4%). Prevalence estimates in Oghi, Shamdhara and Kathai were 10.3%, 11% and 9% respectively. Knowledge and awareness regarding HCV was inadequate among the study population. Conclusions: HCV prevalence in the study area is higher than the overall prevalence in Pakistan. HCV related knowledge and awareness among population in the area is inadequate. There is a need to undertake a large scale population based epidemiological study and to introduce health interventions to control and reverse the spread of HCV in the area and to impart health education and awareness to the masses. (author)

  8. Comparison of a newly developed automated and quantitative hepatitis C virus (HCV) core antigen test with the HCV RNA assay for clinical usefulness in confirming anti-HCV results.

    Science.gov (United States)

    Kesli, Recep; Polat, Hakki; Terzi, Yuksel; Kurtoglu, Muhammet Guzel; Uyar, Yavuz

    2011-12-01

    Hepatitis C virus (HCV) is a global health care problem. Diagnosis of HCV infection is mainly based on the detection of anti-HCV antibodies as a screening test with serum samples. Recombinant immunoblot assays are used as supplemental tests and for the final detection and quantification of HCV RNA in confirmatory tests. In this study, we aimed to compare the HCV core antigen test with the HCV RNA assay for confirming anti-HCV results to determine whether the HCV core antigen test may be used as an alternative confirmatory test to the HCV RNA test and to assess the diagnostic values of the total HCV core antigen test by determining the diagnostic specificity and sensitivity rates compared with the HCV RNA test. Sera from a total of 212 treatment-naive patients were analyzed for anti-HCV and HCV core antigen both with the Abbott Architect test and with the molecular HCV RNA assay consisting of a reverse transcription-PCR method as a confirmatory test. The diagnostic sensitivity, specificity, and positive and negative predictive values of the HCV core antigen assay compared to the HCV RNA test were 96.3%, 100%, 100%, and 89.7%, respectively. The levels of HCV core antigen showed a good correlation with those from the HCV RNA quantification (r = 0.907). In conclusion, the Architect HCV antigen assay is highly specific, sensitive, reliable, easy to perform, reproducible, cost-effective, and applicable as a screening, supplemental, and preconfirmatory test for anti-HCV assays used in laboratory procedures for the diagnosis of hepatitis C virus infection.

  9. Neutralizing activities of caprine antibodies towards conserved regions of the HCV envelope glycoprotein E2

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    El-Shenawy Reem

    2011-08-01

    Full Text Available Abstract Anti HCV vaccine is not currently available and the present antiviral therapies fail to cure approximately half of the treated HCV patients. This study was designed to assess the immunogenic properties of genetically conserved peptides derived from the C-terminal region of HVR-1 and test their neutralizing activities in a step towards developing therapeutic and/or prophylactic immunogens against HCV infection. Antibodies were generated by vaccination of goats with synthetic peptides derived from HCV E2. Viral neutralizing capacity of the generated anti E2 antibodies was tested using in vitro assays. Goats immunized with E2 synthetic peptides termed p412 [a.a 412-419], p430 [a.a 430-447] and p517 [a.a 517-531] generated high titers of antibody responses 2 to 4.5 fold higher than comparable titers of antibodies to the same epitopes in chronic HCV patients. In post infection experiments of native HCV into cultured Huh7.5 cells anti p412 and anti p 517 were proven to be neutralizing to HCV genotype 4a from patients' sera (87.5% and 75% respectively. On the contrary anti p430 exhibited weak viral neutralization capacity on the same samples (31.25%. Furthermore Ab mixes containing anti p430 exhibited reduced viral neutralization properties. From these experiments one could predict that neutralization by Abs towards different E2-epitopes varies considerably and success in the enrichment of neutralization epitope-specific antibodies may be accompanied by favorable results in combating HCV infection. Also, E2 conserved peptides p517 and p412 represent potential components of a candidate peptide vaccine against HCV infection.

  10. Naturally occurring NS3 resistance-associated variants in hepatitis C virus genotype 1: Their relevance for developing countries.

    Science.gov (United States)

    Echeverría, Natalia; Betancour, Gabriela; Gámbaro, Fabiana; Hernández, Nelia; López, Pablo; Chiodi, Daniela; Sánchez, Adriana; Boschi, Susana; Fajardo, Alvaro; Sóñora, Martín; Moratorio, Gonzalo; Cristina, Juan; Moreno, Pilar

    2016-09-02

    Hepatitis C virus (HCV) is a major cause of global morbidity and mortality, with an estimated 130-150 million infected individuals worldwide. HCV is a leading cause of chronic liver diseases including cirrhosis and hepatocellular carcinoma. Current treatment options in developing countries involve pegylated interferon-α and ribavirin as dual therapy or in combination with one or more direct-acting antiviral agents (DAA). The emergence of resistance-associated variants (RAVs) after treatment reveals the great variability of this virus leading to a great difficulty in developing effective antiviral strategies. Baseline RAVs detected in DAA treatment-naïve HCV-infected patients could be of great importance for clinical management and outcome prediction. Although the frequency of naturally occurring HCV NS3 protease inhibitor mutations has been addressed in many countries, there are only a few reports on their prevalence in South America. In this study, we investigated the presence of RAVs in the HCV NS3 serine protease region by analysing a cohort of Uruguayan patients with chronic hepatitis C who had not been treated with any DAAs and compare them with the results found for other South American countries. The results of these studies revealed that naturally occurring mutations conferring resistance to NS3 inhibitors exist in a substantial proportion of Uruguayan treatment-naïve patients infected with HCV genotype 1 enrolled in these studies. The identification of these baseline RAVs could be of great importance for patients' management and outcome prediction in developing countries. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Pilot study for assessment of prevalence of intrafamilial hepatitis C ...

    African Journals Online (AJOL)

    HCV-RNA in saliva of HCV patients provides a biological basis for its potential transmission. HCV viremia is particularly high in HCV patients on hemodialysis. This study aimed to evaluate the prevalence of HCV in saliva of HCV patients with and without renal failure, and the possible role of intrafamilial transmission of the ...

  12. Correlates of HCV seropositivity among familial contacts of HCV positive patients

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    Matera Antonio

    2006-09-01

    Full Text Available Abstract Background Determinants of intrafamilial HCV transmission are still being debated. The aim of this study is to investigate the correlates of HCV seropositivity among familial contacts of HCV positive patients in Italy. Methods A cross-sectional study was conducted with 175 HCV positive patients (index cases, recruited from Policlinico Gemelli in Rome as well as other hospitals in Central Italy between 1995 and 2000 (40% female, mean age 57 ± 15.2 years, and 259 familial contacts. Differences in proportions of qualitative variables were tested with non-parametric tests (χ2, Yates correction, Fisher exact test, and a p value Results Seropositivity for HCV was found in 8.9% of the contacts. From the univariate analysis, risk factors significantly associated to HCV positivity in the contacts were: intravenous drug addiction (p = 0.004 and intercourse with drug addicts (p = 0.005. The only variables associated significantly and independently to HCV seropositivity in patients' contacts were intercourse with drug addicts (OR = 19.28; 95% CI: 2.01 – 184.94, the retirement status from work (OR = 3.76; 95% CI: 1.17 – 11.98, the time of the relationship (OR = 1.06; 95% CI: 1.00 – 1.11 and tattoos (OR = 7.68; 95% CI: 1.00 – 60.20. Conclusion The present study confirms that having intercourse with a drug addict is the most significant risk factor for intrafamilial HCV transmission. The association with retirement status from work could be related to both a long-term relationship with an index case and past exposure to common risk factors.

  13. Infecção pelo vírus da hepatite C em gestantes em Mato Grosso do Sul, 2005-2007 Infección por el virus de la hepatitis C en gestantes en Mato Grosso do Sul, Centro-Oeste de Brasil, 2005-2007 Hepatitis C virus infection among pregnant women in Central-Western Brazil, 2005-2007

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    Clarice Souza Pinto

    2011-10-01

    Full Text Available O estudo teve por objetivo estimar a prevalência da infecção e genótipo do vírus da hepatite C (HCV, bem como determinar a subnotificação de casos. O total de 115.386 gestantes atendidas pelo Programa Estadual de Proteção à Gestante de Mato Grosso do Sul foi submetido à coleta de sangue para a detecção de anti-HCV, de 2005 a 2007. A prevalência da infecção pelo HCV foi de 1,07 casos/1.000. As amostras positivas foram submetidas à detecção do HCV-RNA e genotipadas. O genótipo 1 foi encontrado em 73% das amostras, 24,3% pertenciam ao genótipo 3 e 2,7% ao genótipo 2. A subnotificação de casos de hepatite C foi de 35,5%.El estudio tuvo por objetivo estimar la prevalencia de la infección y genotipo del virus de la hepatitis C (HCV, así como determinar la subnotificación de casos. El total de 115.386 gestantes atendidas por el Programa Estatal de Protección a la Gestante de Mato Grosso do Sul (Centro-Oeste de Brasil fueron sometidas a la colecta de sangre para la detección de anti-HCV, de 2005 a 2007. La prevalencia de la infección por el HCV fue de 1,07 casos/1000. Las muestras positivas fueron sometidas a la detección del HCV-RNA y genotipadas. El genotipo 1 fue encontrado en 73% de las muestras, 24,3% pertenecían al genotipo 3 y 2,7% al genotipo 2. La subnotificación de casos de hepatitis C fue de 35,5%.The study was aimed at estimating the prevalence of infection with and the genotype of hepatitis C virus (HCV, and to determine the extent of underreporting of HCV cases. A total of 115,386 pregnant women seen by the Program for Protection of Pregnancy [Programa Estadual de Proteção à Gestante] of the state of Mato Grosso do Sul, Central-Western Brazil, were tested for anti-HCV antibodies between 2005 and 2007. Prevalence of HCV infection was 1.07 cases per thousand. Positive samples were tested for HCV RNA and genotyped. Genotype 1 was detected in 73% of samples, genotype 3 in 24.3%, and genotype 2 in 2

  14. Prevalence and risk factors of Hepatitis C virus infection in Brazil, 2005 through 2009: a cross-sectional study

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    Pereira Leila MMB

    2013-02-01

    Full Text Available Abstract Background Hepatitis C chronic liver disease is a major cause of liver transplant in developed countries. This article reports the first nationwide population-based survey conducted to estimate the seroprevalence of HCV antibodies and associated risk factors in the urban population of Brazil. Methods The cross sectional study was conducted in all Brazilian macro-regions from 2005 to 2009, as a stratified multistage cluster sample of 19,503 inhabitants aged between 10 and 69 years, representing individuals living in all 26 State capitals and the Federal District. Hepatitis C antibodies were detected by a third-generation enzyme immunoassay. Seropositive individuals were retested by Polymerase Chain Reaction and genotyped. Adjusted prevalence was estimated by macro-regions. Potential risk factors associated with HCV infection were assessed by calculating the crude and adjusted odds ratios, 95% confidence intervals (95% CI and p values. Population attributable risk was estimated for multiple factors using a case–control approach. Results The overall weighted prevalence of hepatitis C antibodies was 1.38% (95% CI: 1.12%–1.64%. Prevalence of infection increased in older groups but was similar for both sexes. The multivariate model showed the following to be predictors of HCV infection: age, injected drug use (OR = 6.65, sniffed drug use (OR = 2.59, hospitalization (OR = 1.90, groups socially deprived by the lack of sewage disposal (OR = 2.53, and injection with glass syringe (OR = 1.52, with a borderline p value. The genotypes 1 (subtypes 1a, 1b, 2b and 3a were identified. The estimated population attributable risk for the ensemble of risk factors was 40%. Approximately 1.3 million individuals would be expected to be anti-HCV-positive in the country. Conclusions The large estimated absolute numbers of infected individuals reveals the burden of the disease in the near future, giving rise to costs for the health care

  15. Prevalence and clinical utility of human papilloma virus genotyping in patients with cervical lesions.

    Science.gov (United States)

    Kaur, Parminder; Aggarwal, Aruna; Nagpal, Madhu; Oberoi, Loveena; Sharma, Swati

    2014-08-01

    Cervical cancer is the commonest cancer among Indian women. High-risk human papilloma virus (HPV) detection holds the potential to be used as a tool to identify women, at risk of subsequent development of cervical cancer. There is a pressing need to identify prevalence of asymptomatic cervical HPV infection in local population. In our study, we explored the prevalence of HPV genotypes and their distribution in women with cervical lesions. Scrape specimens were obtained from 100 women (study group) with cervical abnormalities. HPV was detected with amplicor HPV tests, and the individual genotypes in these specimens were identified by Hybribio Genoarray test kit. Fifty specimens were also collected from females with healthy cervix (control group). The present study also aimed to determine the status of HPV prevalence and its association with different sociodemographic factors. Out of the total number of 100 samples, 10 (10 %) women tested positive for HPV DNA. Among them, HPV 18 was observed in 6, HPV 16 in 2, HPV 52 and HPV 39 in one each. Fifty specimens collected from patients with healthy cervix were not infected with any of the HPV genotype. Our study generates data of HPV prevalence in patients with cervical lesions visiting tertiary care institute. The data generated will be useful for laying guidelines for mass screening of HPV detection, treatment, and prophylaxis.

  16. Liver Fibrosis in HCV Monoinfected and HIV/HCV Coinfected Patients: Dysregulation of Matrix Metalloproteinases (MMPs and Their Tissue Inhibitors TIMPs and Effect of HCV Protease Inhibitors

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    Tiziana Latronico

    2016-03-01

    Full Text Available An imbalance between matrix metalloproteinases (MMPs and tissue inhibitors of metalloproteinases (TIMPs may contribute to liver fibrosis in patients with hepatitis C (HCV infection. We measured the circulating levels of different MMPs and TIMPs in HCV monoinfected and HIV/HCV coinfected patients and evaluated the potential for anti-HCV therapy to modulate MMP and TIMP levels in HCV subjects. We analyzed 83 plasma samples from 16 HCV monoinfected patients undergoing dual or triple anti-HCV therapy, 15 HIV/HCV coinfected patients with undetectable HIV load, and 10 healthy donors (HD. Levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, TIMP-1, and TIMP-2 were measured by a SearchLight Multiplex Immunoassay Kit. MMP-2 and MMP-9 were the highest expressed MMPs among all the analyzed samples and their levels significantly increased in HCV monoinfected and HIV/HCV coinfected subjects compared to HD. TIMP-1 levels were significantly higher in HCV and HIV/HCV subjects compared to HD and were correlated with liver stiffness. These findings raise the possibility of using circulating TIMP-1 as a non-invasive marker of liver fibrosis in HCV infection. A longitudinal study demonstrated that MMP-9 levels significantly decreased (40% reduction from baseline in patients receiving dual as well as triple direct-acting antivirals (DAA anti-HCV therapy, which had no effect on MMP-2, TIMP-1, and TIMP-2. As the dysregulation of MMP-2 and MMP-9 may reflect inflammatory processes in the liver, the decrease of MMP-9 following HCV protease inhibitor treatment suggests a positive effect on the reduction of liver inflammation.

  17. Seroprevalence of Anti-HCV Antibody in Patients with Chronic Kidney Disease before Starting Dialysis Therapy

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    Fareha Jesmin Rabbi

    2017-01-01

    Full Text Available Background: Hepatitis C virus (HCV infection and chronic kidney disease are common and potentially serious medical problems throughout the world. In recent years, it has become clear that these two conditions are linked in several important ways. Indeed, some forms of renal diseases are precipitated by HCV infection and patients with end-stage renal disease (ESRD are at increased risk for acquiring HCV infection. Patients with chronic kidney disease typically show an impaired immune response compared with healthy individuals and also other risk factors related with treatment and management. CKD patients ultimately undergo end stage renal therapy like dialysis for their treatment and survival. Risk factors for the infections are more in dialysis period than in predialytic stages. Like other developing countries CKD patients with HCV infection are very common in our country. For this reason the CKD patients should be properly diagnosed knowing the infection status before dialysis which would help both the patient and doctor to choose their proper treatment approach. Objective: This cross-sectional study was done to know the prevalence of HCV infection in the CKD patients before starting dialysis therapy. Materials and Methods: A total of 197 patients with chronic kidney disease stage five (CKD-V before starting dialysis therapy were included as subjects of this study. Among the CKD patients anti-HCV was detected to see prevalence of hepatitis C virus infection. The patients were also tested for HBsAg to assess co-infection. After collecting all the data of different test results analyses were done by SPSS version 15.0. Results: In this study 195 (99% patients were anti-HCV negative and only two patients (1% were found positive. Conclusion: HCV infection in CKD patients before dialysis should be taken into account so that HCV negative CKD patients would not get the infection during dialysis and standard screening procedures should be taken to

  18. Identification of the transcripts associated with spontaneous HCV clearance in individuals co-infected with HIV and HCV

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    Yue Chen

    2016-11-01

    Full Text Available Abstract Background Infection with human immunodeficiency virus (HIV influences the outcome and natural disease progression of hepatitis C virus (HCV infection. While the majority of HCV mono-infected and HCV/HIV co-infected subjects develop chronic HCV infection, 20–46% of mono- and co-infected subjects spontaneously clear HCV infection. The mechanism underlying viral clearance is not clearly understood. Analysis of differential cellular gene expression (mRNA between HIV-infected patients with persistent HCV infection or spontaneous clearance could provide a unique opportunity to decipher the mechanism of HCV clearance. Methods Plasma RNA from HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV was sequenced using Ion Torrent technology. The sequencing results were analyzed to identify transcripts that are associated with HCV clearance by measuring differential gene expression in HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV. Results We have identified plasma mRNA, the levels of which are significantly elevated (at least 5 fold, False Discovery Rate (FDR <0.05 before HCV infection in subjects who cleared HCV compared to those who remained chronically infected. Upon further analysis of these differentially expressed genes, before and after HCV infection, we found that before HCV infection 12 genes were uniquely upregulated in the clearance group compared to the chronically infected group. Importantly, a number of these 12 genes and their upstream regulators (such as CCL3, IL17D, LBP, SOCS3, NFKBIL1, IRF are associated with innate immune response functions. Conclusions These results suggest that subjects who spontaneously clear HCV may express these unique genes associated with innate immune functions.

  19. NS3 protease resistance-associated substitutions in liver tissue and plasma samples from patients infected by hepatitis C virus genotype 1A or 1B.

    Science.gov (United States)

    Morsica, Giulia; Andolina, Andrea; Merli, Marco; Messina, Emanuela; Hasson, Hamid; Lazzarin, Adriano; Uberti-Foppa, Caterina; Bagaglio, Sabrina

    2017-08-01

    The presence of naturally occurring resistance-associated substitutions (RASs) in the HCV-protease domain has been poorly investigated in the liver, the main site of HCV replication. We evaluated the natural resistance of the virus to NS3 protease inhibitors in liver tissue and plasma samples taken from HCV-infected patients. RASs were investigated by means of viral population sequencing in liver tissue samples from 18 HCV-infected patients harbouring genotype 1a or genotype 1b; plasma samples from 12 of these patients were also available for virological investigation. A discordant genotype was found in two of the 12 patients (16.6%) who provided samples from both compartments. Sequence analysis of the NS3 protease domain showed the presence of RASs in four of the 18 liver tissue samples (22.2%), two of which showed cross-resistance to protease inhibitors in clinical use or phase 2-3 trials. The analysis of the 12 paired tissues and plasma samples excluded the presence of RASs in the plasma compartment. The dominance of discordant genotypes in the paired liver and plasma samples of some HCV-infected patients suggests mixed infection possibly leading to the selective advantage of different genotype in the two compartments. The presence of RASs at intra-hepatic level is not uncommon and may lead to the early emergence of cross-resistant strains.

  20. Cell culture-adaptive mutations of NS5A affect replication of hepatitis C virus differentially depending on the viral genotypes.

    Science.gov (United States)

    Chung, Aeri; Jin, Bora; Han, Kwang-Hyub; Ahn, Sang Hoon; Kim, Seungtaek

    2017-01-01

    Most of HCV RNAs require cell culture-adaptive mutations for efficient replication in cell culture and a number of such mutations have been described including a well-known S2204I substitution mutation in NS5A protein. In contrast, the replication of genotype 2a JFH1 RNA in cell culture does not require any cell culture-adaptive mutation. Rather, the presence of S2204I mutation impaired the JFH1 RNA replication. In this study, we examined the effect of reversions and substitutions of NS5A cell culture-adaptive mutations on virus replication in different genotypic backgrounds after either placing genotype 1a NS5A in the genotype 2a JFH1 or vice versa. The results from this investigation suggest that the S2204I mutation affects HCV RNA replication differentially depending on the viral genotypes but that the effect was not simply explained by the genotypic background. Perhaps, the effect of the S2204I mutation on HCV replication reflects both intra- and intergenic interactions of NS5A protein. J. Med. Virol. 89:146-152, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. IP-10 predicts the first phase decline of HCV RNA and overall viral response to therapy in patients co-infected with chronic hepatitis C virus infection and HIV

    DEFF Research Database (Denmark)

    Falconer, Karolin; Askarieh, Galia; Weis, Nina Margrethe

    2010-01-01

    The aim of this study was to investigate the utility of baseline plasma interferon-gamma inducible protein-10 (IP-10) levels in human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected patients. Baseline IP-10 was monitored during HCV combination therapy in 21 HIV-HCV co-infected...... patients (HCV genotype 1 (n = 16), 2 (n = 2), and 3 (n = 3)). Lower baseline IP-10 was significantly associated with a rapid decline in HCV RNA, in particular with the first phase reduction, and similar cut-off levels ( 600 pg/ml) as in HCV mono-infected patients apply. In conclusion, baseline IP......-10 infected patients, and may thus be useful in encouraging such difficult-to-treat patients to initiate therapy....

  2. Hepatitis C antibody prevalence among Mexico City prisoners injecting legal and illegal substances.

    Science.gov (United States)

    Silverman-Retana, Omar; Serván-Mori, Edson; McCoy, Sandra I; Larney, Sarah; Bautista-Arredondo, Sergio

    2017-12-01

    Hepatitis C virus (HCV) infection is highly prevalent among prisoners and this prevalence estimates reach 64% among prisoners who inject illicit drugs. Prisons are important sites for HCV transmission in the absence of access to sterile injecting equipment; hence, it can be transmitted between prisoners who share contaminated needles and syringes. We aimed to estimate the prevalence of risk factors for anti-HCV prevalence, with particular interest on injecting behavior, and to assess correlates of anti-HCV positivity among Mexico City prisoners. Cross-sectional study based on information -collected in three male and two female prisons in Mexico City during 2010-2011- about sexually transmitted infections, socio-demographics, criminal history, substance use, vitamin injection, tattooing, among others (n=3,910). Weighted multivariable adjusted logistic regression models were estimated to assess the overall and differential odds for anti-HCV due to injecting behavior. Overall prevalence of anti-HCV was 3.3%. This figure rose to 43.1% among prisoners with a history of illicit drug injection. Prisoners with history of vitamin injection showed a similar prevalence of anti-HCV (43.8%). After stratifying by substance injected, the adjusted odds ratio was 9.8 (95% CI: 4.0, 23.8) for illicit drug injection and 11.9 (95% CI: 5.8, 23.8) for illicit drug and vitamin injection. Based on data from the most populous prisons in Mexico City, this study showed that anti-HCV is highly prevalent among prisoners with history of injecting behavior. In this sense, injecting behavior per-se, independent of the substance used, is associated with increased odds of anti-HCV positivity. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Challenge Pools of Hepatitis C Virus Genotypes 1–6 Prototype Strains: Replication Fitness and Pathogenicity in Chimpanzees and Human Liver–Chimeric Mouse Models

    Science.gov (United States)

    Bukh, Jens; Meuleman, Philip; Tellier, Raymond; Engle, Ronald E.; Feinstone, Stephen M.; Eder, Gerald; Satterfield, William C.; Govindarajan, Sugantha; Krawczynski, Krzysztof; Miller, Roger H.; Leroux-Roels, Geert; Purcell, Robert H.

    2010-01-01

    Chimpanzees represent the only animal model for studies of the natural history of hepatitis C virus (HCV). To generate virus stocks of important HCV variants, we infected chimpanzees with HCV strains of genotypes 1–6 and determined the infectivity titer of acute-phase plasma pools in additional animals. The courses of first- and second-passage infections were similar, with early appearance of viremia, HCV RNA titers of >104.7 IU/mL, and development of acute hepatitis; the chronicity rate was 56%. The challenge pools had titers of 103–105 chimpanzee infectious doses/mL. Human liver–chimeric mice developed high-titer infections after inoculation with the challenge viruses of genotypes 1–6. Inoculation studies with different doses of the genotype 1b pool suggested that a relatively high virus dose is required to consistently infect chimeric mice. The challenge pools represent a unique resource for studies of HCV molecular virology and for studies of pathogenesis, protective immunity, and vaccine efficacy in vivo. PMID:20353362

  4. Hepatitis C virus (HCV) RNA profiles among chronic HIV/HCV-coinfected individuals in ESPRIT; spontaneous HCV RNA clearance observed in nine individuals

    DEFF Research Database (Denmark)

    Grint, D; Tedaldi, Ellen; Peters, L

    2017-01-01

    OBJECTIVES: Studies have shown that hepatitis C virus (HCV) RNA levels remain stable over time in HIV/HCV-coinfected individuals taking combination antiretroviral therapy (cART), while spontaneous clearance of HCV RNA during the persistent infection phase has been documented only rarely among tho...

  5. Limiting the access to direct-acting antivirals against HCV: an ethical dilemma.

    Science.gov (United States)

    Gentile, Ivan; Maraolo, Alberto E; Niola, Massimo; Graziano, Vincenzo; Borgia, Guglielmo; Paternoster, Mariano

    2016-11-01

    Hepatitis C virus (HCV) infection affects about 200 million people worldwide and represents a leading cause of liver-related mortality. Eradication of HCV infection, achieved mainly through direct-acting antivirals (DAA), results in a decrease of mortality and an improvement of quality of life. These drugs have a maximal efficacy and an optimal tolerability. However, their high cost precludes a universal access even in wealthy countries. Areas covered: This article deals with the policies adopted for the use of the new anti-HCV drugs, especially in Europe and most of all in Italy, supposedly the developed country with the highest HCV prevalence. The literature search was performed using Pubmed and Web of Science. Moreover, national regulatory institutional websites were consulted. Expert commentary: The current policy of limitation to the access of the DAA presents a series of ethical issues that makes it non-applicable. A 'treat-all' strategy should resolve all ethical dilemmas, by virtue of the wide benefits of anti-HCV treatment not only for the advanced stage of infection, but also for the initial stages. A reduction in price of the drugs is the actual condition to achieve such a change.

  6. Resistance-associated polymorphisms in Dutch hepatitis C genotype 1a patients with and without HIV infection

    NARCIS (Netherlands)

    Lieveld, Faydra I.; Swaans, Niels; Newsum, Astrid M.; Ho, Cynthia K. Y.; Schinkel, Janke; Molenkamp, Richard; van der Meer, Jan T. M.; Arends, Joop E.; Hoepelman, Andy I. M.; Wensing, Anne M. J.; Siersema, Peter D.; van Erpecum, Karel J.; Boland, Greet J.

    2016-01-01

    Background and aim. Resistance-associated variants (RAVs) on the NS3 region of the hepatitis C virus (HCV) may be relevant for antiviral therapy, but data in human immunodeficiency virus (HIV) coinfected patients are scarce. We assessed frequencies of NS3 RAVs in patients infected with HCV genotype

  7. Hepatitis C Virus Genie: A Web 2.0 Interpretation and Analytics Platform for the Versant Hepatitis C Virus Genotype Line Probe Assay Version 2.0.

    Science.gov (United States)

    Dussaq, Alex M; Soni, Abha; Willey, Christopher; Park, Seung L; Harada, Shuko

    2017-01-01

    Hepatitis C virus (HCV) genotyping at our institution is performed using the Versant HCV genotype 2.0 Line Probe Assay (LiPA). The last steps of this procedure are manual, laborious, and error-prone process that involves the comparison of the banding pattern on a test strip to a physical reference table. We developed a web-based HCV genotype interpretation platform that utilizes a scanned image to generate the genotypes, thus minimizing interpretation time and reducing error. HCV Genie 2 utilizes a database of banding patterns in conjuncture with image analysis algorithms to determine the genotype for any number of scanned LiPA strips. HCV Genie 2 is built with client-side JavaScript; allowing the program to run in the user' browser rather than on an unknown server, essentially eliminating data and patient privacy concerns. HCV Genie 2 was tested over 2 months and proved identical to human expert interpretation for 148 samples (>1000 bands identified). Manual intervention was required only for two faint bands and one false-positive band; this was done utilizing the built-in-user interface. Utilizing the original method, the trained laboratory technician interpretation time for 16 samples was 13.8 (±0.96) min as compared to 5.0 (±1.09) min with HCV Genie 2, a 63.8% decrease. In addition to the time savings, the new method provides an additional validation step, which decreases the potential for errors. Our institution has moved exclusively to utilize the new techniques and tools described here. Both experienced technicians and the molecular pathologists at our institution prefer the workflow using HCV Genie. It is easier for the technicians to prepare and document, and the pathologists are more rapidly able to review and confirm results. The use of this tool will lead to increase the quality of patient care delivered through this test methodology by decreasing the potential for error. The algorithms developed here can be ported to similar band identification

  8. Hepatitis C virus Genie: A web 2.0 interpretation and analytics platform for the Versant Hepatitis C virus genotype Line Probe Assay version 2.0

    Directory of Open Access Journals (Sweden)

    Alex M Dussaq

    2017-01-01

    Full Text Available Context: Hepatitis C virus (HCV genotyping at our institution is performed using the Versant HCV genotype 2.0 Line Probe Assay (LiPA. The last steps of this procedure are manual, laborious, and error-prone process that involves the comparison of the banding pattern on a test strip to a physical reference table. Aim: We developed a web-based HCV genotype interpretation platform that utilizes a scanned image to generate the genotypes, thus minimizing interpretation time and reducing error. Subjects and Methods: HCV Genie 2 utilizes a database of banding patterns in conjuncture with image analysis algorithms to determine the genotype for any number of scanned LiPA strips. HCV Genie 2 is built with client-side JavaScript; allowing the program to run in the user' browser rather than on an unknown server, essentially eliminating data and patient privacy concerns. Results: HCV Genie 2 was tested over 2 months and proved identical to human expert interpretation for 148 samples (>1000 bands identified. Manual intervention was required only for two faint bands and one false-positive band; this was done utilizing the built-in-user interface. Utilizing the original method, the trained laboratory technician interpretation time for 16 samples was 13.8 (±0.96 min as compared to 5.0 (±1.09 min with HCV Genie 2, a 63.8% decrease. In addition to the time savings, the new method provides an additional validation step, which decreases the potential for errors. Conclusions: Our institution has moved exclusively to utilize the new techniques and tools described here. Both experienced technicians and the molecular pathologists at our institution prefer the workflow using HCV Genie. It is easier for the technicians to prepare and document, and the pathologists are more rapidly able to review and confirm results. The use of this tool will lead to increase the quality of patient care delivered through this test methodology by decreasing the potential for error. The

  9. HCV-induced autophagosomes are generated via homotypic fusion of phagophores that mediate HCV RNA replication.

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    Linya Wang

    2017-09-01

    Full Text Available Hepatitis C virus (HCV induces autophagy to promote its replication, including its RNA replication, which can take place on double-membrane vesicles known as autophagosomes. However, how HCV induces the biogenesis of autophagosomes and how HCV RNA replication complex may be assembled on autophagosomes were largely unknown. During autophagy, crescent membrane structures known as phagophores first appear in the cytoplasm, which then progress to become autophagosomes. By conducting electron microscopy and in vitro membrane fusion assay, we found that phagophores induced by HCV underwent homotypic fusion to generate autophagosomes in a process dependent on the SNARE protein syntaxin 7 (STX7. Further analyses by live-cell imaging and fluorescence microscopy indicated that HCV-induced phagophores originated from the endoplasmic reticulum (ER. Interestingly, comparing with autophagy induced by nutrient starvation, the progression of phagophores to autophagosomes induced by HCV took significantly longer time, indicating fundamental differences in the biogenesis of autophagosomes induced by these two different stimuli. As the knockdown of STX7 to inhibit the formation of autophagosomes did not affect HCV RNA replication, and purified phagophores could mediate HCV RNA replication, the assembly of the HCV RNA replication complex on autophagosomes apparently took place during the formative stage of phagophores. These findings provided important information for understanding how HCV controlled and modified this important cellular pathway for its own replication.

  10. Seroprevalence study of HCV among hospitalized intravenous drug users in Ahvaz, Iran (2001–2006

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    Seyed Mohammad Alavi

    Full Text Available Summary: Background and aims: Prevalence of hepatitis C virus (HCV in intravenous drug users (IDU varies in different areas according to socioeconomic and geographical circumstances. The present study was performed to determine seroprevalence of HCV in IDU individuals in Ahvaz, Iran. Materials and methods: 142 IDU patients were included in this retrospective study in Ahvaz southwest Iran from 2001 to 2006. Patients were placed in two groups determined by HCV Ab positive or negative status. Data were analyzed using SPSS for Windows (version 11.5; SPSS Inc., USA software. Results: Out of total 142 cases, 74 persons (52.11% had a positive HCV-Ab test according to the ELISA method. There was no difference in age, sex, level of education, residency and co-infection with HIV and hepatitis B virus between HCV-Ab positive (HAP and HCV-Ab negative (HAN groups (p > 0.05. HCV-Ab positivity was significantly related to imprisonment and duration spent in prison [OR: 3.22, 95% (CI 2.61–3.76, p < 0.0001]. Conclusion: Patients with IDU constitute a high-risk group for acquisition of HCV infection. Transmission of HCV via sharing syringe and needle as well as blood transfusion has been a significant source of hepatitis C infection for patients with intravenous drug addiction. Keywords: Intravenous drug user, Hepatitis C virus, Seroprevalence, Ahvaz

  11. Production of infectious genotype 1b virus particles in cell culture and impairment by replication enhancing mutations.

    Directory of Open Access Journals (Sweden)

    Thomas Pietschmann

    2009-06-01

    Full Text Available With the advent of subgenomic hepatitis C virus (HCV replicons, studies of the intracellular steps of the viral replication cycle became possible. These RNAs are capable of self-amplification in cultured human hepatoma cells, but save for the genotype 2a isolate JFH-1, efficient replication of these HCV RNAs requires replication enhancing mutations (REMs, previously also called cell culture adaptive mutations. These mutations cluster primarily in the central region of non-structural protein 5A (NS5A, but may also reside in the NS3 helicase domain or at a distinct position in NS4B. Most efficient replication has been achieved by combining REMs residing in NS3 with distinct REMs located in NS4B or NS5A. However, in spite of efficient replication of HCV genomes containing such mutations, they do not support production of infectious virus particles. By using the genotype 1b isolate Con1, in this study we show that REMs interfere with HCV assembly. Strongest impairment of virus formation was found with REMs located in the NS3 helicase (E1202G and T1280I as well as NS5A (S2204R, whereas a highly adaptive REM in NS4B still allowed virus production although relative levels of core release were also reduced. We also show that cells transfected with the Con1 wild type genome or the genome containing the REM in NS4B release HCV particles that are infectious both in cell culture and in vivo. Our data provide an explanation for the in vitro and in vivo attenuation of cell culture adapted HCV genomes and may open new avenues for the development of fully competent culture systems covering the therapeutically most relevant HCV genotypes.

  12. Retreatment with peg-interferon and ribavirin in patients with chronic hepatitis C virus genotype 2 or 3 infection with prior relapse

    DEFF Research Database (Denmark)

    Lagging, Martin; Rembeck, Karolina; Rauning Buhl, Mads

    2013-01-01

    Uncertainty remains regarding the efficacy of retreatment with current standard-of-care peg-interferon (peg-IFN) and ribavirin among patients infected with hepatitis C virus (HCV) genotypes 2 or 3 with relapse after prior therapy.......Uncertainty remains regarding the efficacy of retreatment with current standard-of-care peg-interferon (peg-IFN) and ribavirin among patients infected with hepatitis C virus (HCV) genotypes 2 or 3 with relapse after prior therapy....

  13. Naturally occurring resistance mutations within the core and NS5B regions in hepatitis C genotypes, particularly genotype 5a, in South Africa.

    Science.gov (United States)

    Prabdial-Sing, N; Blackard, J T; Puren, A J; Mahomed, A; Abuelhassan, W; Mahlangu, J; Vermeulen, M; Bowyer, S M

    2016-03-01

    Approximately 1 million South Africans are infected with Hepatitis C virus (HCV). The standard of care (SOC) in South Africa is combination therapy (pegylated interferon and ribavirin). HCV genotypes and/or mutations in the core/non-structural regions have been associated with response to therapy and/or disease progression. This study examines mutations in the core (29-280 amino acids, including ∼ 90 E1 amino acids) and NS5B (241-306 amino acids) regions on pre-treatment isolates from patients attending Johannesburg hospitals or asymptomatic South African blood donors. Diversity within known CD4+ and CD8+ T-cell epitopes was also explored. Samples grouped into subtypes 1a(N = 10) 1b(N = 12), 3a(N = 5), 4a(N = 3) and 5a(N = 61). Two mutations, associated with interferon resistance-R70Q and T110N-were present in 29 genotype 5a core sequences. No resistance mutation to NS5B nucleotide inhibitors, sofosbuvir was found. Six putative CD8+ and one CD4+ T-cell epitope sequence in the core region showed binding scores of <300 IC50nM to HLA alleles frequently observed in the South African population. No known CD8+ and CD4+ T-cell epitopes were mapped in the NS5B region. The analysis begs the question whether those infected with genotype 5a will benefit better on interferon-free combination therapies. This study provides new insight into one of the lesser studied HCV genotypes and compares the diversity seen in a large pre-treatment cohort with other subtypes. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Risk Behaviors for HIV and HCV Infection Among People Who Inject Drugs in Hai Phong, Viet Nam, 2014.

    Science.gov (United States)

    Duong, Huong Thi; Jarlais, Don Des; Khuat, Oanh Hai Thi; Arasteh, Kamyar; Feelemyer, Jonathan; Khue, Pham Minh; Giang, Hoang Thi; Laureillard, Didier; Hai, Vinh Vu; Vallo, Roselyne; Michel, Laurent; Moles, Jean Pierre; Nagot, Nicolas

    2017-06-13

    We examined the potential for HIV and hepatitis C (HCV) transmission across persons who inject drugs (PWID), men-who-have-sex-with-men (MSM) and female commercial sex workers (CSW) PWID and the potential for sexual transmission of HIV from PWID to the general population in Hai Phong, Viet Nam. Using respondent driven and convenience sampling we recruited 603 participants in 2014. All participants used heroin; 24% used non-injected methamphetamine. HIV prevalence was 25%; HCV prevalence was 67%. HIV infection was associated with HCV prevalence and both infections were associated with length of injecting career. Reported injecting risk behaviors were low; unsafe sexual behavior was high among MSM-PWID and CSW-PWID. There is strong possibility of sexual transmission to primary partners facilitated by methamphetamine use. We would suggest future HIV prevention programs utilize multiple interventions including "treatment as prevention" to potential sexual transmission of HIV among MSM and CSW-PWID and from PWID to the general population.

  15. Efficient cell culture system for hepatitis C virus genotype 7a

    DEFF Research Database (Denmark)

    2013-01-01

    Genotype 7a has been identified recently, thus not much is known about the biology of this new, major HCV genotype. The present inventors developed hepatitis C virus 7a/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced...

  16. Challenge pools of hepatitis C virus genotypes 1-6 prototype strains: replication fitness and pathogenicity in chimpanzees and human liver-chimeric mouse models

    DEFF Research Database (Denmark)

    Bukh, Jens; Meuleman, Philip; Tellier, Raymond

    2010-01-01

    Chimpanzees represent the only animal model for studies of the natural history of hepatitis C virus (HCV). To generate virus stocks of important HCV variants, we infected chimpanzees with HCV strains of genotypes 1-6 and determined the infectivity titer of acute-phase plasma pools in additional a...

  17. Low prevalence of hepatitis B and C among tuberculosis patients in Duhok Province, Kurdistan: Are HBsAg and anti-HCV prerequisite screening parameters in tuberculosis control program?

    Science.gov (United States)

    Merza, Muayad A; Haji, Safer M; Alsharafani, Abid Mohialdeen Hasan; Muhammed, Shivan U

    2016-09-01

    Viral hepatitis, particularly hepatitis B virus (HBV) and hepatitis C virus (HCV), infections and tuberculosis (TB) are a global public health concern. Co-infection with HBV or HCV among TB patients may potentiate the risk of hepatotoxicity induced by anti-TB drugs. Hence, the aim of this study was to identify the prevalence of HBV and HCV among TB patients included in the Duhok National Tuberculosis Program (NTP). The Duhok NTP Center is a specialized institution in Duhok City, Iraq, concerned with management and follow-up of TB patients. A cross-sectional study was conducted at the center between June 2015 and May 2016. All documented TB patients were analyzed on the basis of socio-demographic and other characteristics. Thereafter, all patients underwent screening for hepatitis B surface antigen (HBsAg), anti-HCV, and anti-HIV using enzyme-linked immunosorbent assay (ELISA). The results obtained were analyzed by entering the data in binary format into a Microsoft Excel spreadsheet. A p value of Kurdistan, the negative history of injection drug use, and adherence to universal infection-control measures, including vaccination for HBV. Both history of dental intervention and belonging to a Syrian population were independent risk factors for HBV/TB co-infection. Copyright © 2016 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

  18. Analysis of hepatitis C virus core/NS5A protein co-localization using novel cell culture systems expressing core-NS2 and NS5A of genotypes 1-7

    DEFF Research Database (Denmark)

    Galli, Andrea; Scheel, Troels K H; Prentoe, Jannick C

    2013-01-01

    Hepatitis C virus (HCV) is an important human pathogen infecting hepatocytes. With the advent of infectious cell culture systems, the HCV particle assembly and release processes are finally being uncovered. The HCV core and NS5A proteins co-localize on cytoplasmic lipid droplets (c......LDs) or on the endoplasmic reticulum (ER) at different stages of particle assembly. Current knowledge on assembly and release is primarily based on studies in genotype 2a cell culture systems; however, given the high genetic heterogeneity of HCV, variations might exist among genotypes. Here, we developed novel HCV strain...... JFH1-based recombinants expressing core-NS2 and NS5A from genotypes 1-7, and analysed core and NS5A co-localization in infected cells. Huh7.5 cells were transfected with RNA of core-NS2/NS5A recombinants and putative adaptive mutations were analysed by reverse genetics. Adapted core-NS2/NS5A...

  19. High HCV seroprevalence and HIV drug use risk behaviors among injection drug users in Pakistan

    Directory of Open Access Journals (Sweden)

    Zafar Tariq

    2006-08-01

    Full Text Available Abstract Introduction HIV and HCV risk behaviors among injection drug users (IDUs in two urban areas in Pakistan were identified. Methods From May to June 2003, 351 IDUs recruited in harm-reduction drop-in centers operated by a national non-governmental organization in Lahore (Punjab province and Quetta (Balochistan province completed an interviewer-administered survey and were tested for HIV and HCV. Multivariable logistic regression identified correlates of seropositivity, stratifying by site. All study participants provided written, informed consent. Results All but two were male; median age was 35 and Discussion Despite no HIV cases, overall HCV prevalence was very high, signaling the potential for a future HIV epidemic among IDUs across Pakistan. Programs to increase needle exchange, drug treatment and HIV and HCV awareness should be implemented immediately.

  20. Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection

    DEFF Research Database (Denmark)

    Hézode, Christophe; Hirschfield, Gideon M; Ghesquiere, Wayne

    2015-01-01

    OBJECTIVE: To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin. DESIGN: In this Phase 2b double-blind, placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30...

  1. Prevalence of hepatitis C Virus infection among hemophiliacs in Central Brazil

    Directory of Open Access Journals (Sweden)

    Adriana P Barbosa

    2002-07-01

    Full Text Available In order to investigate the hepatitis C virus (HCV infection prevalence and risk factors in hemophiliacs in Central Brazil, 90 patients were interviewed and serum samples tested for HCV RNA and anti-HCV antibodies. An overall prevalence of 63.3% (CI 95%: 53.0-72.7 was found. Multivariate analysis of risk factors showed that number of blood transfusions was significantly associated with this infection. Most hemophiliacs received locally produced cryoprecipitate. All infected patients were transfused before the screening of blood units for anti-HCV. However, hemophiliacs who received exclusively screened cryoprecipitate were HCV negative. It confirms the expected decline in transfusion-acquired hepatitis C.

  2. Prevalence of Cervical Infection and Genotype Distribution of Human Papilloma Virus Among Females in Da Nang, Vietnam.

    Science.gov (United States)

    Van, Song Nguyen; Khac, Minh Nguyen; Dimberg, Jan; Matussek, Andreas; Henningsson, Anna J

    2017-03-01

    The goal of the present study was to determine the prevalence and distribution of high-risk human papilloma virus (HPV) genotypes in women from two districts in and around Da Nang city, Vietnam. All participants were randomly selected, 200 from the Hai Chau district and 200 from the Son Tra district. The detection and genotyping of HPV were performed by real-time polymerase chain reaction (PCR) technique. Out of a total of 400 women, we found that 38 (9.5%) were infected with a high-risk HPV genotype, the most prevalent genotypes being 16, 18, 58 and 59. By assessment of the HPV findings in relation to sociodemographic characteristics, we found significant differences between the two study districts and between the age groups, as well as differences associated with occupation and the use of contraceptives. The proportion of high-risk genotypes other than 16 and 18 was relatively high, and since the HPV genotype distribution is known to vary greatly across populations, the information from this study can be used for planning of screening and vaccination programs in Da Nang. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Hepatitis B, C, and D virus infection showing distinct patterns between injection drug users and the general population.

    Science.gov (United States)

    Chen, Fei; Zhang, Jian; Guo, Fengfan; Wen, Bo; Luo, Shan; Yuan, Dongping; Lin, Yingbiao; Ou, Wensheng; Tang, Ping; Dai, Guozhi; Li, Fangfang; Liu, Wenpei; Qu, Xiaowang

    2017-02-01

    Hepatitis B, C, and D virus (HBV, HCV, and HDV) infections are known to be prevalent in injection drug users (IDUs); however, the relationship between the molecular epidemiologic features of hepatitis virus infection in high-risk individuals and the general population has not yet been established. In total, 1049 IDUs and 672 individuals who underwent physical examinations at Chenzhou hospital, Hunan Province, China, were enrolled. HBV, HCV, and HDV infections were screened with serologic tests in both populations. HBsAg-positive, anti-HCV IgG-positive, and anti-HDV IgG-positive samples were further confirmed by polymerase chain reaction, quantitative polymerase chain reaction, and DNA sequencing. Significantly higher HBV (21.54 vs 16.52%, P = 0.01), HCV (45.95% vs 1.34%, P infections were detected in IDUs compared with the general population. The dual infection of HBV/HCV or HBV/HDV was also significantly higher in IDUs than in the general population. HBV genotype B and HDV genotype II were dominants in both populations. HCV infection showed genotype 6a (49.52%) dominant in IDUs, but genotype 1b accounted for 50% infection, which was followed by genotype 6a (33.33%) in the general population. Higher viral loads were associated with HBV genotype B and HCV genotype 6a compared with non-dominant genotypic infections. HBV and HDV infections shared similar patterns by IDUs and the general populations, and HCV infection exhibited distinct features between two populations. Our results suggest different molecular epidemiologic characteristics of HBV, HCV, and HDV infection in two populations. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  4. Prevalence of Hepatitis C Virus Infection and Its Risk Factors among Patients Attending Rwanda Military Hospital, Rwanda.

    Science.gov (United States)

    Umumararungu, Esperance; Ntaganda, Fabien; Kagira, John; Maina, Naomi

    2017-01-01

    In Rwanda, the prevalence of viral hepatitis (HCV) is poorly understood. The current study investigated the prevalence and risk factors of HCV infection in Rwanda. A total of 324 patients attending Rwanda Military Hospital were randomly selected and a questionnaire was administered to determine the risk factors. Blood was collected and screened for anti-HCV antibodies and seropositive samples were subjected to polymerase chain reaction method. Hematology abnormalities in the HCV infected patients were also investigated. Anti-HCV antibody and active HCV infection were found in 16.0% and 9.6% of total participants, respectively. Prevalence was highest (28.4%; 19/67) among participants above 55 years and least (2.4%; 3/123) among younger participants (18-35 years). There was a significant ( P = 0.031) relationship between place of residence and HCV infection with residents of Southern Province having significantly higher prevalence. The hematological abnormalities observed in the HCV infected patients included leukopenia (48.4%; 15/52), neutropenia (6.5%; 2/52), and thrombocytopenia (25.8%; 8/52). The HCV infection was significantly higher in the older population (>55 years) and exposure to injection from traditional practitioners was identified as a significant ( P = 0.036) risk factor of infection. Further studies to determine the factors causing the high prevalence of HCV in Rwanda are recommended.

  5. Prevalence of hepatitis B, hepatitis C and human immunodeficiency ...

    African Journals Online (AJOL)

    Background. Hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV are common blood-borne infections unevenly distributed across regions in Nigeria. Few population-based prevalence studies have been done in Nigeria. Objective. To determine the prevalence of HBV, HCV and HIV and risk factors for infection with ...

  6. Seroprevalence of HIV, HBV, HCV, and HTLV among Pregnant Women in Southwestern Nigeria.

    Science.gov (United States)

    Opaleye, Oluyinka Oladele; Igboama, Magdalene C; Ojo, Johnson Adeyemi; Odewale, Gbolabo

    2016-01-01

    Sexually transmitted infections (STIs) are major public health challenge especially in developing countries. This study was designed to determine the prevalence of Hepatitis B virus (HBV), Hepatitis C Virus (HCV), Human immunodeficiency virus (HIV), and Human T-cell lymphotropic Virus type I (HTLV-I) among pregnant women attending antenatal clinic, in Ladoke Akintola University Teaching Hospital, Osogbo, and South-Western Nigeria. One hundred and eighty two randomly selected pregnant women were screened for HBsAg, anti-HCV, anti-HIV and HTLV-1 IgM antibodies using commercially available ELISA kit. Of the 182 blood samples of pregnant women screened whose age ranged from 15-49 years, 13 (7.1%), 5 (2.7%), 9 (4.9%), and 44 (24.2%) were positive for HBsAg, anti-HCV, anti-HIV, and HTLV-1 IgM antibodies, respectively. The co-infection rate of 0.5% was obtained for HBV/HCV, HBV/HIV, HIV/HTLV-1, and HCV/HTLV-1 while 1.1% and 0% was recorded for HBV/HTLV-1 and HCV/HIV co-infections, respectively. Expected risk factors such as history of surgery, circumcision, tattooing and incision showed no significant association with any of the viral STIs (P > 0.05). This study shows that there is the need for a comprehensive screening of all pregnant women for HBsAg, anti-HCV, anti-HIV and HTLV-1 to prevent mother to child transmission of these viral infections and its attending consequences.

  7. Early virologic response and IL28B polymorphisms in patients with chronic hepatitis C genotype 3 treated with peginterferon alfa-2a and ribavirin.

    Science.gov (United States)

    Scherzer, Thomas-Matthias; Hofer, Harald; Staettermayer, Albert Friedrich; Rutter, Karoline; Beinhardt, Sandra; Steindl-Munda, Petra; Kerschner, Heidrun; Kessler, Harald H; Ferenci, Peter

    2011-05-01

    Polymorphisms of the IL28B gene (rs12979860 and rs8099917) are associated with high sustained virological response (SVR) rates in HCV genotype 1 patients. This study analyzes the impact of these IL28B polymorphisms on early treatment response (weeks 2 and 4) and SVR in HCV genotype 3 patients. rs12979860 and rs8099917 were analyzed by the Step-OnePlus Real-time PCR system in 71 out of 72 Caucasian HCV genotype 3 patients participating, at our center, in a randomized study comparing 400mg with 800 mg ribavirin/day. HCV RNA was determined at weeks 2 and 4 of 180 μg/week peginterferon alfa-2a/ribavirin treatment. Sixty-nine patients completed the treatment and follow-up. rs12979860 genotyping revealed that 27 (37.5%) patients had C/C, 39 (54.2%) T/C, and 5 (6.9%) T/T. Thirteen patients (18.1%) became HCV RNA negative at week 2 and an additional 30 (41.7%) at week 4 (rapid virologic response; RVR); thus a total of 43 had a RVR (C/C: 77.8%; T/C or T/T: 50.0%). Irrespective of the ribavirin dose, the viral load decline was larger than in those with the T allele (T/C or T/T) (week 2: 4.46; [0.36-6.02] median; [range] vs. 3.50; [0.14-5.62]; log IU HCV-RNA/ml; p<0.001; week 4: 4.97; [1.21-6.20] vs. 4.49; [1.16-6.23]; p=0.003). Despite the faster initial viral response in C/C carriers, SVR rates were not different compared to T-allele carriers. Results of the SNP in the rs8099917 region were similar. IL28B polymorphisms modulate early virologic response to peginterferon/ribavirin treatment. In contrast to HCV genotype 1 patients, no effect on SVR rates was observed in genotype 3 patients. The clinical relevance of an earlier viral decline in C/C patients needs to be determined. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  8. HCV-RNA quantification in liver bioptic samples and extrahepatic compartments, using the abbott RealTime HCV assay.

    Science.gov (United States)

    Antonucci, FrancescoPaolo; Cento, Valeria; Sorbo, Maria Chiara; Manuelli, Matteo Ciancio; Lenci, Ilaria; Sforza, Daniele; Di Carlo, Domenico; Milana, Martina; Manzia, Tommaso Maria; Angelico, Mario; Tisone, Giuseppe; Perno, Carlo Federico; Ceccherini-Silberstein, Francesca

    2017-08-01

    We evaluated the performance of a rapid method to quantify HCV-RNA in the hepatic and extrahepatic compartments, by using for the first time the Abbott RealTime HCV-assay. Non-tumoral (NT), tumoral (TT) liver samples, lymph nodes and ascitic fluid from patients undergoing orthotopic-liver-transplantation (N=18) or liver resection (N=4) were used for the HCV-RNA quantification; 5/22 patients were tested after or during direct acting antivirals (DAA) treatment. Total RNA and DNA quantification from tissue-biopsies allowed normalization of HCV-RNA concentrations in IU/μg of total RNA and IU/10 6 liver-cells, respectively. HCV-RNA was successfully quantified with high reliability in liver biopsies, lymph nodes and ascitic fluid samples. Among the 17 untreated patients, a positive and significant HCV-RNA correlation between serum and NT liver-samples was observed (Pearson: rho=0.544, p=0.024). Three DAA-treated patients were HCV-RNA "undetectable" in serum, but still "detectable" in all tested liver-tissues. Differently, only one DAA-treated patient, tested after sustained-virological-response, showed HCV-RNA "undetectability" in liver-tissue. HCV-RNA was successfully quantified with high reliability in liver bioptic samples and extrahepatic compartments, even when HCV-RNA was "undetectable" in serum. Abbott RealTime HCV-assay is a good diagnostic tool for HCV quantification in intra- and extra-hepatic compartments, whenever a bioptic sample is available. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Factors Associated with Spontaneous Clearance of Hepatitis C Virus in Chinese Population

    Directory of Open Access Journals (Sweden)

    Fei Kong

    2014-01-01

    Full Text Available Hepatitis C virus (HCV infections spontaneously clear in approximately 15–45% of infected individuals. Factors which influence spontaneous HCV clearance remain to be identified. The purpose of the present study was to identify variables associated with spontaneous HCV clearance in a referred population of Chinese patients. The prevalence of host, viral, and environmental factors known to influence the outcome of HCV infections was compared in 92 HCV spontaneous clearance subjects and 318 HCV persistent infection subjects. Univariate and multivariate analyses were performed to identify those factors associated with spontaneous HCV clearance. In univariate analysis, female gender, a history of icteric hepatitis, serologic evidence of concurrent HBV infection, and rs12979860 CC genotype were positively associated with spontaneous HCV clearance, while alcohol consumption was negatively associated with clearance. In multivariate analysis, female gender, a history of icteric hepatitis, concurrent HBV infection, and rs12979860 CC genotype remained independent variables associated with spontaneous HCV clearance. Spontaneous HCV clearance is more likely to occur in females, subjects with a history of icteric hepatitis, HBV coinfections, and those with the rs12979860 CC genotype.

  10. Combination of sofosbuvir and daclatasvir in the treatment of genotype 3 chronic hepatitis C virus infection in patients on maintenance hemodialysis

    Directory of Open Access Journals (Sweden)

    Sperl J

    2017-06-01

    Full Text Available Jan Sperl,1 Sona Frankova,1 Miluse Kreidlova,2 Dusan Merta,3 Monika Tothova,4 Julius Spicak1 1Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 2Institute of Medical Biochemistry and Laboratory Medicine, General University Hospital, Charles University, 3Department of Anesthesiology, Resuscitation and Intensive Care, Institute for Clinical and Experimental Medicine, 4Dialysis Center Motol, Fresenius Medical Care, Prague, Czech Republic Abstract: Chronic hepatitis C virus infection (HCV has a negative impact on the long-term survival of recipients of kidney transplants. HCV should be treated in hemodialyzed patients before their enlistment for kidney transplantation in order to avoid the reactivation of virus after transplantation. Direct-acting antivirals represent the current standard of care in hemodialyzed patients with HCV genotypes 1 and 4; in patients with genotypes 2 or 3, the optimal regimen is yet to be established. Sofosbuvir (SOF and daclatasvir (DCV represent an antiviral pangenotypic regimen with favorable pharmacokinetics in hemodialyzed patients. We retrospectively evaluated safety and efficacy of the combination of SOF and DCV in the treatment of genotype 3a chronic HCV in six male patients (mean age of 39 years, range 25–53 years with end-stage renal disease on maintenance hemodialysis; these patients were treated with a reduced dose of SOF (one half of a 400 mg tablet and 60 mg of DCV once daily. The anticipated treatment duration was 12 weeks. Initial HCV RNA ranged from 120,000 to 11,000,000 IU/mL. Two of the six patients had compensated liver cirrhosis based on shear-wave elastography result. All of the patients completed a 12-week treatment. Viremia became negative on treatment and remained negative 12 weeks after the end of therapy in all the patients. All of them (6/6, 100% achieved sustained virological response, including two with cirrhosis and two with HCV RNA >6,000,000 IU

  11. Impact of IL28B-Related Single Nucleotide Polymorphisms on Liver Histopathology in Chronic Hepatitis C Genotype 2 and 3

    DEFF Research Database (Denmark)

    Rembeck, Karolina; Alsiö, Asa; Christensen, Peer Brehm

    2012-01-01

    Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of HCV infection as well as outcome following peginterferon and ribavirin therapy among HCV genotype 1 infected patients. The present stu...

  12. Health Beliefs and Co-morbidities Associated with Appointment-Keeping Behavior Among HCV and HIV/HCV Patients.

    Science.gov (United States)

    Pundhir, Pooja; North, Carol S; Fatunde, Oluwatomilade; Jain, Mamta K

    2016-02-01

    Appointment-keeping behavior is an important requisite for HCV linkage and treatment initiation. In this study we examine what impact hepatitis C (HCV) knowledge and attitudes has on appointment-keeping behavior among a cohort of HCV and HCV/HIV patients. Knowledge scores and attitude scales, obtained from a cross-sectional survey, were correlated with proportion of appointments kept 1 year prior to taking the survey. Independent risk factors for missing appointments were examined by multiple regression analysis. 292 HCV patients completed the survey, and 149 (51%) were co-infected with HIV. HCV patients kept 67.5 ± 17.4% of their total appointments and a similar proportion (67 ± 38.2) of Liver Clinic appointments, but they attended a higher proportion (73 ± 24.4) of Primary Care Clinic appointments. However, certain health beliefs, psychiatric illness, and HIV co-infection were independently associated with lower levels of appointment-keeping behavior. HCV knowledge was not associated with appointment-keeping behavior. Health beliefs, psychiatric illness, and HIV co-infection are associated with missing appointments, but no link between knowledge and appointment keeping behavior is apparent. In order to increase engagement into HCV care, HCV care coordination programs need to focus on addressing health beliefs and providing resources to those at highest risk for missing appointments.

  13. The role of biochemical variations and genotype testing in determining the virological response of patients infected with hepatitis C virus

    Directory of Open Access Journals (Sweden)

    Abid Shoukat

    2018-01-01

    Full Text Available Background: In hepatitis C virus (HCV, infection viral and IL28B genotype along with many clinical and biochemical factors can influence response rates to pegylated interferon plus ribavirin (Peg-IFN-a/R therapy and progression to chronic hepatitis C (CHC. Aims: The present study was conducted to determine the effect of biochemical and risk factors on treatment outcome in CHC patients in relation to their viral and host genotype. Settings and Design: The present study was a prospective Pe- IFN efficacy study consisting of Peg-IFN-a/R therapy for 24–48 weeks including 250 HCV infected patients. Materials and Methods: Biochemical parameters were determined by Beckman Coulter AU680 automated analyzer. HCV and Interleukin 28B (IL28B genotyping were carried out by polymerase chain reaction-restriction fragment length polymorphism and viral load was determined by quantitative real-time PCR. Results: Wild outnumbered the variant genotypes in rs 12979860, rs 12980275, and rs 8099917 SNP of IL28B gene. Sustained virological response (SVR SVR and viral genotype were significantly associated with age, hepatic steatosis, low-grade varices, and serum aspartate transaminase levels (at the end of treatment (P < 0.05. In addition, SVR was significantly influenced by body mass index (BMI, insulin resistance, serum low-density lipoprotein , and ferritin levels (P < 0.05. Viral genotype 1 infected patients had higher serum cholesterol and triglyceride levels (P < 0.05. Conclusions: Although the IL28B sequence variation is the major factor that can influence response rates to antiviral therapy, viral and biochemical factors also have a definite role to play in the diagnosis, etiology, and treatment outcome in HCV-infected patients.

  14. Ghrelin gene polymorphism as a genetic biomarker for prediction of therapy induced clearance in Egyptian chronic HCV patients.

    Science.gov (United States)

    Hamdy, Marwa; Kassim, Samar Kamal; Khairy, Eman; Maher, Mohsen; Mansour, Khaled Amr; Albreedy, Ashraf M

    2018-04-05

    Ghrelin (GHRL) has important implications for liver disease. It has anti-inflammatory effects, regulates cell proliferation, modulates the fibrogenic response and protects liver tissue. Genetic variations in the GHRL gene may play a crucial role in the development of chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Therefore, we examined the association of GHRL gene polymorphisms (rs26312 and rs27647), and its serum level to virologic responses to combined sofosbuvir and Simeprevir therapy for a course of 12 successive weeks in Egyptian chronic hepatitis C (CHC) patients. Human genomic and clinical data were collected from 100 Egyptian participants in this study, 90 HCV patients who received sofosbuvir and Simeprevir and 10 non-HCV healthy subjects. Genotyping of GHRL rs26312 and rs27647, were determined with the TaqMan qRT-PCR allele detection assay. The serum GHRL concentrations were determined using enzyme-linked immunosorbent assay (ELISA). GHRL polymorphisms (rs26312 and rs27647) genotype distributions and allele frequencies did not differ between HCV patients and normal healthy subjects or between patient groups when compared according to the therapeutic response. In addition, we found significant lower serum GHRL levels in CHC patients compared with the healthy controls. However, there was no significant association of the GHRL rs26312 and rs27647 polymorphisms with GHRL levels in CHC patients. We conclude that GHRL SNPs (rs26312 and rs27647) do not affect response to combined sofosbuvir and Simeprevir treatment in chronic Egyptian HCV patients. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Packaging of HCV-RNA into lentiviral vector

    International Nuclear Information System (INIS)

    Caval, Vincent; Piver, Eric; Ivanyi-Nagy, Roland; Darlix, Jean-Luc; Pagès, Jean-Christophe

    2011-01-01

    Highlights: ► Description of HCV-RNA Core-D1 interactions. ► In vivo evaluation of the packaging of HCV genome. ► Determination of the role of the three basic sub-domains of D1. ► Heterologous system involving HIV-1 vector particles to mobilise HCV genome. ► Full length mobilisation of HCV genome and HCV-receptor-independent entry. -- Abstract: The advent of infectious molecular clones of Hepatitis C virus (HCV) has unlocked the understanding of HCV life cycle. However, packaging of the genomic RNA, which is crucial to generate infectious viral particles, remains poorly understood. Molecular interactions of the domain 1 (D1) of HCV Core protein and HCV RNA have been described in vitro. Since compaction of genetic information within HCV genome has hampered conventional mutational approach to study packaging in vivo, we developed a novel heterologous system to evaluate the interactions between HCV RNA and Core D1. For this, we took advantage of the recruitment of Vpr fusion-proteins into HIV-1 particles. By fusing HCV Core D1 to Vpr we were able to package and transfer a HCV subgenomic replicon into a HIV-1 based lentiviral vector. We next examined how deletion mutants of basic sub-domains of Core D1 influenced HCV RNA recruitment. The results emphasized the crucial role of the first and third basic regions of D1 in packaging. Interestingly, the system described here allowed us to mobilise full-length JFH1 genome in CD81 defective cells, which are normally refractory to HCV infection. This finding paves the way to an evaluation of the replication capability of HCV in various cell types.

  16. Packaging of HCV-RNA into lentiviral vector

    Energy Technology Data Exchange (ETDEWEB)

    Caval, Vincent [INSERM U966, Universite Francois Rabelais de Tours, Faculte de Medecine, 10 Bd. Tonnelle, 37000 Tours (France); Piver, Eric [INSERM U966, Universite Francois Rabelais de Tours, Faculte de Medecine, 10 Bd. Tonnelle, 37000 Tours (France); Service de Biochimie et Biologie Moleculaire, CHRU de Tours (France); Ivanyi-Nagy, Roland; Darlix, Jean-Luc [LaboRetro, ENS-Lyon INSERM, U758, 46 Allee d' Italie, 69364 Lyon (France); Pages, Jean-Christophe, E-mail: jean-christophe.pages@univ-tours.fr [INSERM U966, Universite Francois Rabelais de Tours, Faculte de Medecine, 10 Bd. Tonnelle, 37000 Tours (France); Service de Biochimie et Biologie Moleculaire, CHRU de Tours (France)

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer Description of HCV-RNA Core-D1 interactions. Black-Right-Pointing-Pointer In vivo evaluation of the packaging of HCV genome. Black-Right-Pointing-Pointer Determination of the role of the three basic sub-domains of D1. Black-Right-Pointing-Pointer Heterologous system involving HIV-1 vector particles to mobilise HCV genome. Black-Right-Pointing-Pointer Full length mobilisation of HCV genome and HCV-receptor-independent entry. -- Abstract: The advent of infectious molecular clones of Hepatitis C virus (HCV) has unlocked the understanding of HCV life cycle. However, packaging of the genomic RNA, which is crucial to generate infectious viral particles, remains poorly understood. Molecular interactions of the domain 1 (D1) of HCV Core protein and HCV RNA have been described in vitro. Since compaction of genetic information within HCV genome has hampered conventional mutational approach to study packaging in vivo, we developed a novel heterologous system to evaluate the interactions between HCV RNA and Core D1. For this, we took advantage of the recruitment of Vpr fusion-proteins into HIV-1 particles. By fusing HCV Core D1 to Vpr we were able to package and transfer a HCV subgenomic replicon into a HIV-1 based lentiviral vector. We next examined how deletion mutants of basic sub-domains of Core D1 influenced HCV RNA recruitment. The results emphasized the crucial role of the first and third basic regions of D1 in packaging. Interestingly, the system described here allowed us to mobilise full-length JFH1 genome in CD81 defective cells, which are normally refractory to HCV infection. This finding paves the way to an evaluation of the replication capability of HCV in various cell types.

  17. Drug Abuse, HIV, and HCV in Asian Countries.

    Science.gov (United States)

    Hser, Yih-Ing; Liang, Di; Lan, Yu-Ching; Vicknasingam, Balasingam Kasinather; Chakrabarti, Amit

    2016-09-01

    Drug abuse and co-occurring infections are associated with significant morbidity and mortality. Asian countries are particularly vulnerable to the deleterious consequences of these risks/problems, as they have some of the highest rates of these diseases. This review describes drug abuse, HIV, and hepatitis C (HCV) in Asian countries. The most commonly used illicit drugs include opioids, amphetamine-type stimulants (ATS), cannabis, and ketamine. Among people who inject drugs, HIV rates range from 6.3 % in China to 19 % in Malaysia, and HCV ranges from 41 % in India and Taiwan to 74 % in Vietnam. In the face of the HIV epidemics, drug policies in these countries are slowly changing from the traditional punitive approach (e.g., incarcerating drug users or requiring registration as a drug user) to embrace public health approaches, including, for example, community-based treatment options as well as harm reduction approaches to reduce needle sharing and thus HIV transmission. HIV and HCV molecular epidemiology indicates limited geographic diffusion. While the HIV prevalence is declining in all five countries, use of new drugs (e.g., ATS, ketamine) continues to increase, as well as high-risk sexual behaviors associated with drug use-increasing the risk of sexual transmission of HIV, particularly among men who have sex with men. Screening, early intervention, and continued scaling up of therapeutic options (drug treatment and recovery support, ART, long-term HIV and HCV care for drug users) are critical for effective control or continued reduction of drug abuse and co-infections.

  18. HCV Infection and B-Cell Lymphomagenesis

    Directory of Open Access Journals (Sweden)

    Masahiko Ito

    2011-01-01

    Full Text Available Hepatitis C virus (HCV has been recognized as a major cause of chronic liver diseases worldwide. It has been suggested that HCV infects not only hepatocytes but also mononuclear lymphocytes including B cells that express the CD81 molecule, a putative HCV receptor. HCV infection of B cells is the likely cause of B-cell dysregulation disorders such as mixed cryoglobulinemia, rheumatoid factor production, and B-cell lymphoproliferative disorders that may evolve into non-Hodgkin's lymphoma (NHL. Epidemiological data indicate an association between HCV chronic infection and the occurrence of B-cell NHL, suggesting that chronic HCV infection is associated at least in part with B-cell lymphomagenesis. In this paper, we aim to provide an overview of recent literature, including our own, to elucidate a possible role of HCV chronic infection in B-cell lymphomagenesis.

  19. Assessing the impact of educational campaigns on controlling HCV among women in prison settings

    Science.gov (United States)

    Mushayabasa, S.; Bhunu, C. P.; Smith?, Robert J.

    2012-04-01

    Prior studies have shown that imprisonment is a major risk factor for hepatitis C infection, with the risk of infection directly proportional to the length of incarceration. Women are at least twice as likely as men to contract HCV as they have limited access to information, health services and safe intravenous drug injecting equipments. We develop a mathematical model to assess the impact of educational campaigns on controlling HCV among women in prison settings. Equilibria for the model are determined and their stability are examined. Population-level effects of increased educational campaigns to encourage safe injecting practices among women in prison are evaluated through numerical simulations. The results suggest that educating women prisoners about abstaining from intravenous drug misuse may significantly reduce HCV prevalence among women in prison settings. Targeted education campaigns, which are effective at stopping transmission of HCV more than 80% of the time, will be highly effective at controlling the disease among women in prisons.

  20. High rate of hepatitis C virus (HCV) recurrence in HIV-infected individuals with spontaneous HCV RNA clearance

    DEFF Research Database (Denmark)

    Peters, L; Mocroft, A; Soriano, V

    2014-01-01

    OBJECTIVES: Following resolution of hepatitis C virus (HCV) infection, recurrence has been shown to occur in some persons with repeated exposure to HCV. We aimed to investigate the rate and factors associated with HCV RNA recurrence among HIV-1-infected patients with prior spontaneous HCV RNA cle......-up. Our findings underline the importance of maintaining focus on preventive measures to reduce IDU and sharing of contaminated needles. Clinicians should maintain a high degree of vigilance to identify patients with new HCV infection early....

  1. [Determination of drug resistance mutations of NS3 inhibitors in chronic hepatitis C patients infected with genotype 1].

    Science.gov (United States)

    Şanlıdağ, Tamer; Sayan, Murat; Akçalı, Sinem; Kasap, Elmas; Buran, Tahir; Arıkan, Ayşe

    2017-04-01

    Direct-acting antiviral agents (DAA) such as NS3 protease inhibitors is the first class of drugs used for chronic hepatitis C (CHC) treatment. NS3 inhibitors (PI) with low genetic barrier have been approved to be used in the CHC genotype 1 infections, and in the treatment of compensated liver disease including cirrhosis together with pegile interferon and ribavirin. Consequently, the development of drug resistance during DAA treatment of CHC is a major problem. NS3 resistant variants can be detected before treatment as they can occurnaturally. The aim of this study was to investigate new and old generation NS3 inhibitors resistance mutations before DAA treatment in hepatitis C virus (HCV) that were isolated from CHC. The present study was conducted in 2015 and included 97 naive DAA patients infected with HCV genotype 1, who were diagnosed in Manisa and Kocaeli cities of Turkey. Magnetic particle based HCV RNA extraction and than RNA detection and quantification were performed using commercial real-time PCR assay QIASypmhony + Rotorgene Q/ArtusHCV QS-RGQ and COBAS Ampliprep/COBAS TaqMan HCV Tests. HCV NS3 viral protease genome region was amplified with PCR and mutation analysis was performed by Sanger dideoxy sequencing technique of NS3 protease codons (codon 32-185). HCV NS3 protease inhibitors; asunaprevir, boceprevir, faldaprevir, grazoprevir, pariteprevir, simeprevir and telaprevir were analysed for resistant mutations by Geno2pheno-HCV resistance tool. HCV was genotyped in all patients and 88 patients (n= 88/97, 91%) had genotype 1. Eight (n= 8/97, 8.2%) and 80 (n= 80/97, 82.4%) HCC patients were subgenotyped as 1a and 1b, respectively. Many aminoacid substitutions and resistance mutations were determined in 39/88 (44%) patients in the study group. Q80L, S122C/N, S138W were defined as potential substitutions (6/88 patients; 7%); R109K, R117C, S122G, I132V, I170V, N174S were described as potential resistance (34/88 patients; 39%); V36L, T54S, V55A, Q80H were

  2. In Silico Design and Experimental Validation of siRNAs Targeting Conserved Regions of Multiple Hepatitis C Virus Genotypes.

    Directory of Open Access Journals (Sweden)

    Mahmoud ElHefnawi

    Full Text Available RNA interference (RNAi is a post-transcriptional gene silencing mechanism that mediates the sequence-specific degradation of targeted RNA and thus provides a tremendous opportunity for development of oligonucleotide-based drugs. Here, we report on the design and validation of small interfering RNAs (siRNAs targeting highly conserved regions of the hepatitis C virus (HCV genome. To aim for therapeutic applications by optimizing the RNAi efficacy and reducing potential side effects, we considered different factors such as target RNA variations, thermodynamics and accessibility of the siRNA and target RNA, and off-target effects. This aim was achieved using an in silico design and selection protocol complemented by an automated MysiRNA-Designer pipeline. The protocol included the design and filtration of siRNAs targeting highly conserved and accessible regions within the HCV internal ribosome entry site, and adjacent core sequences of the viral genome with high-ranking efficacy scores. Off-target analysis excluded siRNAs with potential binding to human mRNAs. Under this strict selection process, two siRNAs (HCV353 and HCV258 were selected based on their predicted high specificity and potency. These siRNAs were tested for antiviral efficacy in HCV genotype 1 and 2 replicon cell lines. Both in silico-designed siRNAs efficiently inhibited HCV RNA replication, even at low concentrations and for short exposure times (24h; they also exceeded the antiviral potencies of reference siRNAs targeting HCV. Furthermore, HCV353 and HCV258 siRNAs also inhibited replication of patient-derived HCV genotype 4 isolates in infected Huh-7 cells. Prolonged treatment of HCV replicon cells with HCV353 did not result in the appearance of escape mutant viruses. Taken together, these results reveal the accuracy and strength of our integrated siRNA design and selection protocols. These protocols could be used to design highly potent and specific RNAi-based therapeutic

  3. Novel infectious cDNA clones of hepatitis C virus genotype 3a (strain S52) and 4a (strain ED43): genetic analyses and in vivo pathogenesis studies

    DEFF Research Database (Denmark)

    Gottwein, Judith; Scheel, Troels; Callendret, Benoit

    2010-01-01

    Previously, RNA transcripts of cDNA clones of hepatitis C virus (HCV) genotypes 1a (strains H77, HCV-1, and HC-TN), 1b (HC-J4, Con1, and HCV-N), and 2a (HC-J6 and JFH1) were found to be infectious in chimpanzees. However, only JFH1 was infectious in human hepatoma Huh7 cells. We performed genetic...... analysis of HCV genotype 3a (strain S52) and 4a (strain ED43) prototype strains and generated full-length consensus cDNA clones (pS52 and pED43). Transfection of Huh7.5 cells with RNA transcripts of these clones did not yield cells expressing HCV Core. However, intrahepatic transfection of chimpanzees...... resulted in robust infection with peak HCV RNA titers of approximately 5.5 log(10) international units (IU)/ml. Genomic consensus sequences recovered from serum at the times of peak viral titers were identical to the sequences of the parental plasmids. Both chimpanzees developed acute hepatitis...

  4. Adaptive mutations enhance assembly and cell-to-cell transmission of a high-titer hepatitis C virus genotype 5a Core-NS2 JFH1-based recombinant

    DEFF Research Database (Denmark)

    Mathiesen, Christian K; Prentoe, Jannick; Meredith, Luke W

    2015-01-01

    UNLABELLED: Recombinant hepatitis C virus (HCV) clones propagated in human hepatoma cell cultures yield relatively low infectivity titers. Here, we adapted the JFH1-based Core-NS2 recombinant SA13/JFH1C3405G,A3696G (termed SA13/JFH1orig), of the poorly characterized genotype 5a, to Huh7.5 cells......-titer production of diverse HCV strains would be advantageous. Our study offers important functional data on how cell culture-adaptive mutations identified in genotype 5a JFH1-based HCVcc permit high-titer culture by affecting HCV genesis through increasing virus assembly and HCV fitness by enhancing the virus...... specific infectivity and cell-to-cell transmission ability, without influencing the biophysical particle properties. High-titer HCVcc like the one described in this study may be pivotal in future vaccine-related studies where large quantities of infectious HCV particles are necessary....

  5. Hepatitis C Virus Resistance Testing in Genotype 1: The Changing Role in Clinical Utility.

    Science.gov (United States)

    Molino, Suzanne; Martin, Michelle T

    2017-09-01

    To review the role and utility of baseline resistance testing with currently available and pipeline genotype 1 hepatitis C virus (HCV) treatment. Authors reviewed liver meeting abstracts for data on currently-available and pipeline genotype 1 retreatment regimens from January 1, 2015, to March 23, 2017. Additional trials were identified from a review of clinicaltrials.gov using the pipeline medication names. Authors identified reports of current and pipeline genotype 1 retreatment regimens. Seven references were clinical study results presented at the meetings of the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver, and 2 studies were from clinicaltrials.gov . Retreatment trial data of currently available salvage regimens indicate that baseline NS5A resistance-associated substitutions (RASs) may decrease sustained virological response (SVR) rates when retreating with ledipasvir/sofosbuvir but are not affected when using elbasvir/grazoprevir + sofosbuvir + ribavirin, paritaprevir/ritonavir/ombitasvir + dasabuvir + sofosbuvir, or sofosbuvir/velpatasvir + ribavirin. Pipeline data indicate that baseline NS5A RASs do not affect SVR rates when retreating with sofosbuvir/velpatasvir/voxilaprevir or glecaprevir/pibrentasvir. Baseline resistance testing was used for decisional support for 3 clinical scenarios in patients with HCV genotype 1 infection at the time of manuscript submission. Pending the approval of 2 new direct-acting antiviral regimens in the third quarter of 2017, the rapidly evolving HCV treatment guidelines will likely reflect a decreased clinical utility for resistance testing.

  6. Hepatitis B virus in Pakistan: a systematic review of prevalence, risk factors, awareness status and genotypes.

    Science.gov (United States)

    Ali, Muhammad; Idrees, Muhammad; Ali, Liaqat; Hussain, Abrar; Ur Rehman, Irshad; Saleem, Sana; Afzal, Samia; Butt, Sadia

    2011-03-06

    In Pakistan, there are estimated 7-9 million carriers of hepatitis B virus (HBV) with a carrier rate of 3-5%. This article reviews the available literature about the prevalence, risk factors, awareness status and genotypes of the HBV in Pakistan by using key words; HBV prevalence, risk factors, awareness status and genotypes in Pakistani population in PubMed, PakMediNet, Directory of Open Access Journals (DOAJ) and Google Scholar. One hundred and six different studies published from 1998 to 2010 were included in this study. Weighted mean and standard deviation were determined for each population group. The percentage of hepatitis B virus infection in general population was 4.3318% ± 1.644%, healthy blood donors (3.93% ± 1.58%), military recruits (4.276% ± 1.646%), healthcare persons (3.25% ± 1.202%), pregnant women (5.872% ± 4.984), prisoners (5.75% ± 0.212%), surgical patients (7.397% ± 2.012%), patients with cirrhosis (28.87% ± 11.90%), patients with HCC (22% ± 2.645%), patients with hepatitis (15.896% ± 14.824%), patients with liver diseases (27.54% ± 6.385%), multiple transfused patients (6.223% ± 2.121%), opthalmic patients (3.89% ± 1.004%) and users of injectable drugs (14.95% ± 10.536%). Genotype D (63.71%) is the most prevalent genotype in Pakistani population. Mass vaccination and awareness programs should be initiated on urgent basis especially in populations with HBV infection rates of more than 5%.

  7. Hepatitis C virus infection among drug injectors in St Petersburg, Russia: social and molecular epidemiology of an endemic infection.

    Science.gov (United States)

    Paintsil, Elijah; Verevochkin, Sergei V; Dukhovlinova, Elena; Niccolai, Linda; Barbour, Russell; White, Edward; Toussova, Olga V; Alexander, Louis; Kozlov, Andrei P; Heimer, Robert

    2009-11-01

    To understand the epidemiology and transmission patterns of hepatitis C virus (HCV), the predominant blood borne-pathogen infecting injection drug users (IDUs), in a part of the former Soviet Union. Cross-sectional respondent-driven sample of IDUs. St Petersburg, Russia. A total of 387 IDUs were recruited in late 2005 and throughout 2006. Participants were surveyed to collect demographic, medical and both general and dyad-specific drug injection and sexual behaviors. A blood sample was collected to detect antibodies to hepatitis C and to amplify viral RNA for molecular analysis. The molecular data, including genotypes, were analyzed spatially and linkage patterns were compared to the social linkages obtained by respondent-driven sampling (RDS) for chains of respondents and among the injection dyads. HCV infection was all but ubiquitous: 94.6% of IDUs were HCV-seropositive. Among the 209 viral sequences amplified, genotype 3a predominated (n = 119, 56.9%), followed by 1b (n = 61, 29.2%) and 1a (n = 25, 11.9%). There was no significant clustering of genotypes spatially. Neither genotypes nor closely related sequences were clustered within RDS chains. Analysis of HCV sequences from dyads failed to find associations of genotype or sequence homology within pairs. Genotyping reveals that there have been at least five unique introductions of HCV genotypes into the IDU community in St Petersburg. Analysis of prevalent infections does not appear to correlate with the social networks of IDUs, suggesting that simple approaches to link these networks to prevalent infections, rather than incident transmission, will not prove meaningful. On a more positive note, the majority of IDUs are infected with 3a genotype that is associated with sustained virological response to antiviral therapy.

  8. In vitro neutralization of HCV by goat antibodies against peptides encompassing regions downstream of HVR-1 of E2 glycoprotein.

    Science.gov (United States)

    Tabll, Ashraf A; Atef, Khaled; Bader El Din, Noha G; El Abd, Yasmine S; Salem, Ahmed; Sayed, Ahmed A; Dawood, Reham M; Omran, Moataza H; El-Awady, Mostafa K

    2014-01-01

    This article aims at testing several in vitro systems with various viral sources and cell lines for propagation of HCV to evaluate goat antibodies raised against three E2 epitopes in viral neutralization experiments. Four human cell lines (Huh-7, Huh-7.5, HepG2, and CaCo2) were tested using two different HCV viral sources; Genotype 4 infected sera and J6/JFH HCV cc particles. Neutralization capacity of goat Abs against conserved E2 epitopes; p412 (a.a 412-419), p517 (a.a 517-531), and p430 (a.a 430-447) were examined in the above mentioned in vitro systems. Although infection with patients' sera seems to mimic the in vitro situation, it has limited replication rates as compared with HCV cc particularly in Huh7.5 cells. Non-HCV adapted Huh-7 cells were also found susceptible for transfection with J6/JFH virus but at much slower kinetics. The results of the neutralization assay showed that anti p412 and anti p517 were highly neutralizing to HCVcc. Our data demonstrate that antibodies directed against the viral surface glycoprotein E2 reduced the infectivity of the J6/JFH virus and are promising agents for immunotherapy and HCV vaccine development.

  9. Prevalence of hepatitis C in the general population in the Netherlands.

    NARCIS (Netherlands)

    Slavenburg, S.; Verduyn-Lunel, F.M.; Hermsen, J.T.; Melchers, W.J.G.; Morsche, R.H.M. te; Drenth, J.P.H.

    2008-01-01

    BACKGROUND: Chronic hepatitis C virus (HCV) is transmitted by blood-blood contact and this leads to high HCV prevalence in risk populations such as haemophilia patients and intravenous drug users. The prevalence in the general Dutch population is unknown, although it appears to be very low in

  10. Sero prevalence of hepatitis -C antibodies in blood donors

    International Nuclear Information System (INIS)

    Rahman, M.U.; Akhtar, G.N.; Lodhi, Y.

    2002-01-01

    Objective: To assess the prevalence of anti HCV antibodies in blood donors. Design: The retrospective sero-epidemiological data of the institute of Hematology and Blood Transfusion Service, Punjab over a period of one year after starting HCV screening, was analyzed to estimate the percentage prevalence. Setting; The data was obtained regularly from the blood units established by this institute at the pablic sector hospitals and retesting on initially reactive serum sample by EIA was done at the Institute. Subjects: A total of 166183 directed first time donors or replacement blood donors aged 18-60 years who donated blood at these blood banks or at mobile sessions have been included in the study. All initially reactive donors who tested non-reactive on EIA were excluded from the study. Main outcome Measures: Assessment of prevalence of HCV in blood donors. Results: 4.45% of the total donors intially tested reactive of these 0.36 % were atsety reactive on intial screening. Further testing by EIA, 4.1%. Conclusions: The blood transfusion service started screening for HCV in April 2000 and the prevalence of HCV, amongst the transfusion transmitted infections (TTIs) being screened for in the Punjab, is the highest. It is almost double the prevalence of HBV and several thousand time that of HIV. Meticulous and total screening coverage is needed to curtail impending catastrophe. With experience, the choice of testing methodology might have to be reviewed. (author)

  11. Metabolic syndrome is associated with poor treatment response to antiviral therapy in chronic hepatitis C genotype 3 patients.

    Science.gov (United States)

    Aziz, Hafsa; Gill, Uzma; Raza, Abida; Gill, Muzaffar L

    2014-05-01

    Hepatitis C viral (HCV) infection is caused by an RNA virus. HCV infection is considered to induce systemic disease that causes steatosis, alters lipid metabolism, and results in metabolic syndrome. This study aimed to investigate the therapeutic outcome in HCV genotype 3 patients with metabolic syndrome. A total of 621 HCV-positive patients who visited the hospital for treatment were screened. Among these, 441 patients were enrolled for antiviral therapy. These enrolled patients were assessed for metabolic syndrome according to the International Diabetes Federation criteria. Group A included patients with metabolic syndrome and group B included patients without metabolic syndrome. All patients received peginterferon-α2a (180 μg/week) and ribavirin (10 mg/kg/day) for 6 months. The prevalence of metabolic syndrome in chronic HCV patients was 37.9%. We observed that metabolic syndrome was more common among female compared with male participants (43.9 vs. 28.8%, P=0.005). It was found that sustained virologic response (SVR) rates were significantly higher in the patients in group B (without metabolic syndrome) compared with the patients in group A who had metabolic syndrome (72.2 vs. 43.7%, Pmetabolic syndrome and a correlation of metabolic syndrome with nonresponse to antiviral therapy was observed. An interesting correlation among metabolic syndrome, age, and SVR was found: with age, SVR decreases, while metabolic syndrome increases. Metabolic syndrome has an influence on therapeutic outcomes in terms of SVR. Moreover, this information can identify patients who might have a low chance of attaining an SVR and a timely decision may protect the patients from the adverse effects of therapy.

  12. Assessing the Long-Term Impact of Treating Hepatitis C Virus (HCV-Infected People Who Inject Drugs in the UK and the Relationship between Treatment Uptake and Efficacy on Future Infections.

    Directory of Open Access Journals (Sweden)

    Hayley Bennett

    Full Text Available The prevalence of the hepatitis C virus (HCV remains high amongst people who inject drugs (PWID and accounts for the majority of newly acquired infections. This study aims to quantify the value of treatment amongst PWID with more efficacious treatments and at increased uptake rates, with respect to the avoidance of future infections and subsequent long-term complications of HCV.A dynamic HCV transmission and disease progression model was developed, incorporating acute and chronic infection and their long-term complications (decompensated cirrhosis, cancer, liver transplant and mortality, with the potential for HCV transmission to other PWID prior to successful treatment. The model was populated with prevalence and therapy data from a UK setting. Scenarios of current standard of care (SoC treatment efficacy and uptake were compared to anticipated sustained virologic response (SVR rates of 90-100% and increased uptake over varied horizons.SoC led to modest reductions in prevalence; >5% after 200 years. New treatments achieving 90% SVR could reduce prevalence below 5% within 60 years at current uptake rates or within 5 years if all patients are treated. Amongst 4,240 PWID, chronic HCV infections avoided as a result of increasing treatment uptake over the period 2015-2027 ranged from 20-580 and 34-912 with SoC and 90% SVR rates respectively. The reduction in downstream HCV infections due to increasing treatment uptake resulted in an approximate discounted gain of 300 life-years (from avoiding reduced life expectancy from HCV infection and a gain of 1,700 QALYs (from avoiding the disutility of HCV infection and related complications, with a projected £5.4 million cost saving.While improved SVR profiles led to reductions in modelled prevalence, increased treatment uptake was the key driver of future infections avoided. Increased treatment among PWID with new more efficacious therapies could significantly change the future dynamics, cost and health

  13. Association of IL28B SNPs rs12979860 and rs8099917 on Hepatitis C Virus-RNA Status in Donors/Recipients of Living Donor Liver Transplantation.

    Directory of Open Access Journals (Sweden)

    King-Wah Chiu

    Full Text Available To investigate the effect of IL28B single nucleotide polymorphisms (SNPs (rs8099917 and rs12979860 in the donors and recipients on the outcome of Hepatitis C virus-RNA clearance after living donor liver transplantation (LDLT. The rs8099917 and rs12979860 genotypes in 50 donor and recipients pairs were explored on the pre-operative day (POD and post-operative day 30 (POD30. There was a significant difference in HCV-RNA clearance before (12%, 6/50 and after (48%, 24/50 liver transplantation (P < 0.001. The rs8099917 genotype TT was dominant in both the recipients (82%, 41/50 and donors (86%, 43/50, but had no significant effect on HCV-RNA clearance (87.5%, 21/24 and recurrence (76.9%, 20/26 after LDLT. One recipient was detected with genotype GG on POD, which changed to genotype GT on POD30. Prevalence of rs12979860 genotype CT was 98% (49/50 recipient and 92% (46/50 donor and prevalence of genotype CC was 2% (1/50 recipient and 8% (4/50 donor on POD and POD30, respectively. Of the 4 recipients with rs12979860 genotype CC on POD30, 3 recipients (12.5%, 3/24 exhibited HCV clearance and 1 experienced recurrence (3.9%, 1/26, however, this was not statistically significant. In conclusion, alterations in IL28B SNP genotype may occur after LDLT, leading to modifications in the host genome or donor proteome by HCV. This predicted mechanism will need to be investigated further.

  14. Seroprevalence of HCV and HIV infection among clients of the nation's longest-standing statewide syringe exchange program: A cross-sectional study of Community Health Outreach Work to Prevent AIDS (CHOW).

    Science.gov (United States)

    Salek, Thomas P; Katz, Alan R; Lenze, Stacy M; Lusk, Heather M; Li, Dongmei; Des Jarlais, Don C

    2017-10-01

    The Community Health Outreach Work to Prevent AIDS (CHOW) Project is the first and longest-standing statewide integrated and funded needle and syringe exchange program (SEP) in the US. Initiated on O'ahu in 1990, CHOW expanded statewide in 1993. The purpose of this study is to estimate the prevalences of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection, and to characterize risk behaviors associated with infection among clients of a long-standing SEP through the analysis of the 2012 CHOW evaluation data. A cross-sectional sample of 130 CHOW Project clients was selected from January 1, 2012 through December 31, 2012. Questionnaires captured self-reported exposure information. HIV and HCV antibodies were detected via rapid, point-of-care FDA-approved tests. Log-binomial regressions were used to estimate prevalence proportion ratios (PPRs). A piecewise linear log-binomial regression model containing 1 spline knot was used to fit the age-HCV relationship. The estimated seroprevalence of HCV was 67.7% (95% confidence interval [CI]=59.5-75.8%). HIV seroprevalence was 2.3% (95% CI=0-4.9%). Anti-HCV prevalence demonstrated age-specific patterns, ranging from 31.6% through 90.9% in people who inject drugs (PWID) HIV prevalence compared with HCV prevalence reflects differences in transmissibility of these 2 blood-borne pathogens and suggests much greater efficacy of SEP for HIV prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Prevalence of hepatitis B and hepatitis C virus co-infection in India: A systematic review and meta-analysis.

    Science.gov (United States)

    Desikan, Prabha; Khan, Zeba

    2017-01-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) have several important similarities including worldwide distribution, hepato-tropism, similar modes of transmission and the ability to induce chronic infection that may lead to liver cirrhosis and hepatocellular carcinoma. Since both viruses are individually known to cause the pathologies mentioned above, co-infection with both HBV and HCV would be expected to be linked with higher morbidity as well as mortality and impact healthcare resource utilisation. Precise estimate of the prevalence of HBV/HCV co-infection would be needed to formulate policy decisions and plan communal health interventions. This systematic review and meta-analysis, therefore, aims to understand the prevalence of HBV and HCV co-infection in India based on the available literature. Following PRISMA guidelines, primary studies reporting the prevalence of HBV/HCV co-infection in India were retrieved through searches conducted in PubMed, Google SCHOLAR, Medline, Cochrane Library, WHO reports, Indian and International journals online. All online searches were conducted between December 2016 and February 2017. Meta-analysis was carried out using StatsDirect statistical software. Thirty studies published between 2000 and 2016 conducted across six regions of India were included in this review. The pooled HBV/HCV co-infection prevalence rate across the thirty studies was 1.89% (95% confidence intervals [CI] = 1.2%-2.4%). A high heterogeneity was observed between prevalence estimates. The HBV/HCV co-infection prevalence in different subgroups varied from 0.02% (95% CI = 0.0019%-0.090%) to 3.2% (95% CI = 1.3%-5.9%). The pooled prevalence of HBV/HCV co-infection in India was found to be 1.89%. This systematic review and meta-analysis revealed high prevalence of HBV/HCV co-infection in chronic liver patients, followed by HIV-positive patients, and then followed by persons who inject drugs and kidney disease patients.

  16. Occult HCV Infection (OCI) Diagnosis in Cirrhotic and Non-cirrhotic Naïve Patients by Intra-PBMC Nested Viral RNA PCR.

    Science.gov (United States)

    Abd Alla, Mohamed Darwish Ahmed; Elibiary, Saleh Ahmed; Wu, George Y; El-Awady, Mostafa Kamel

    2017-12-28

    Background and Aims: Occult HCV infections (OCIs) include IgG antibody seronegative cryptogenic (COCIs), as well as seropositive secondary naïve (SNOCIs) and experienced (SEOCIs) cases. We used peripheral-blood-mononuclear-cell (PBMC)-PCR to evaluate COCIs and SNOCIs prevalence, serum HCV spontaneous disappearance (SCSD) in naïve cirrhotics and non-cirrhotics, intra-PBMC HCV-RNA strands in relation to cirrhosis density in naïve non-viremia cases, and HCV-RNA seroconversion after 1 year of solitary naïve intra-PBMC infection. Methods: The anti-HCV IgG antibody-positive naïve-patients ( n = 785) were classified into viremic ( n = 673) and non-viremic [ n = 112, including non-cirrhotics ( n = 55) and cirrhotics ( n = 57)], and 62 controls without evidence of HCV-infection. Controls and post-HCV non-viremia cases ( n = 62+112 = 174) were submitted to hepatic Fibroscan-Elastography evaluation. All subjects ( n = 847) were screened for intra-PBMC HCV-RNA sense and antisense strands by nested-PCR. Results: Naïve-OCI cases (4.84%) that were diagnosed by PBMC-PCR significantly raised the total numbers of HCV-infection to 714 ( p = 0.01). The percent positivity of SNOCIs (34.82%) was significantly higher than for asymptomatic-COCIs (3.125%, p = 0.0001). Comparing PBMC-PCR with single-step-reverse-transcription (SRT)-PCR for identification of SCSD in naïve IgG antibody-positive non-viremia patients ( n = 112) revealed a decline in SCSD prevalence by PBMC-PCR (from 14.27% to 9.3%), regardless of presence of hepatic cirrhosis ( p = 0.03). SCSD was found to be higher by PBMC-PCR in non-cirrhotics compared to cirrhotics ( p = 0.0001), with an insignificant difference when using SRT-PCR ( p = 0.45). Intra-PBMC HCV-RNA infection was significantly more frequent in cirrhotics compared to both non-cirrhotics and controls ( p < 0.0005). An increased hepatic fibrosis density was recognized in intra-PBMC HCV-RNA infection with sense ( p = 0.0001) or antisense strand ( p = 0

  17. Prevalence of Human Papillomavirus Genotypes Among Women With High-Grade Cervical Lesions in Beijing, China

    Science.gov (United States)

    Xiao, Meizhu; Xu, Qiuxiang; Li, Hongyan; Gao, Huiqiao; Bie, Yachun; Zhang, Zhenyu

    2016-01-01

    Abstract The aim of the study is to investigate the prevalence of high-risk human papillomavirus (hr-HPV) genotypes among Han women with high-grade cervical lesions in Beijing, China. Cervical cell specimens from patients with histopathologically confirmed cervical lesions at 7 hospitals in Beijing were examined with a validated HPV kit for 13 hr-HPV genotypes during the study period. The patients were divided into a low-grade cervical lesions group (cervical intraepithelial neoplasia grade 1, CIN1) and a high-grade cervical lesions group (CIN2+, including cervical intraepithelial neoplasia grade 2, CIN2; cervical intraepithelial neoplasia grade 3, CIN3; squamous cervical cancer, SCC; and adenocarcinoma of the cervix, ACC) based on the histopathology results. A total of 2817 eligible patients were enrolled, including 610 cases identified as CIN1 and 2207 as CIN2+. The hr-HPV positive rates in the CIN1 and CIN2+ groups were 78.2% (477/610) and 93.3% (2060/2207), respectively. The most frequently detected genotypes were HPV16, 58, 52 and18 in the CIN1 group and HPV16, 58, 33, and 52 in the CIN2+ group, in descending order of prevalence. In addition, the prevalence of HPV18 among the patients with ACC was 28.6% (14/49), significantly >7.2% (54/752) prevalence among the SCC patients (P HPV infections gradually deceased to 44.2% in the CIN2 patients, 36.7% in the CIN3 patients, and 35.3% in the cervical cancer (CC) patients, which included SCC and ACC patients. In cases of multiple hr-HPV infections in the CIN2+ group, double infections accounted for ∼76.6%, and HPV16+58, HPV16+52, and HPV16+18 were the most common combinations, in descending order. The most frequent combination for triple infections was HPV16+58+31, with a rate of 4.2%. The highest positive rate occurred in the ≤24 year-old group for all types of cervical lesions. The prevalence of HPV genotypes in the targeted population with high-grade cervical lesions differs from that of other countries. This

  18. HCV IRES-mediated core expression in zebrafish.

    Directory of Open Access Journals (Sweden)

    Ye Zhao

    Full Text Available The lack of small animal models for hepatitis C virus has impeded the discovery and development of anti-HCV drugs. HCV-IRES plays an important role in HCV gene expression, and is an attractive target for antiviral therapy. In this study, we report a zebrafish model with a biscistron expression construct that can co-transcribe GFP and HCV-core genes by human hepatic lipase promoter and zebrafish liver fatty acid binding protein enhancer. HCV core translation was designed mediated by HCV-IRES sequence and gfp was by a canonical cap-dependent mechanism. Results of fluorescence image and in situ hybridization indicate that expression of HCV core and GFP is liver-specific; RT-PCR and Western blotting show that both core and gfp expression are elevated in a time-dependent manner for both transcription and translation. It means that the HCV-IRES exerted its role in this zebrafish model. Furthermore, the liver-pathological impact associated with HCV-infection was detected by examination of gene markers and some of them were elevated, such as adiponectin receptor, heparanase, TGF-β, PDGF-α, etc. The model was used to evaluate three clinical drugs, ribavirin, IFNα-2b and vitamin B12. The results show that vitamin B12 inhibited core expression in mRNA and protein levels in dose-dependent manner, but failed to impact gfp expression. Also VB12 down-regulated some gene transcriptions involved in fat liver, liver fibrosis and HCV-associated pathological process in the larvae. It reveals that HCV-IRES responds to vitamin B12 sensitively in the zebrafish model. Ribavirin did not disturb core expression, hinting that HCV-IRES is not a target site of ribavirin. IFNα-2b was not active, which maybe resulted from its degradation in vivo for the long time. These findings demonstrate the feasibility of the zebrafish model for screening of anti-HCV drugs targeting to HCV-IRES. The zebrafish system provides a novel evidence of using zebrafish as a HCV model organism.

  19. Prevalence of human papillomavirus genotypes associated with cervical and breast cancers in iran.

    Science.gov (United States)

    Hossein, Rassi; Behzad, Salehi; Tahar, Mohammadian; Azadeh, Nahavandi Araghi

    2013-12-01

    Cancer is a multi-step disease, and infection with a DNA virus could play a role in one or more of the steps in this pathogenic process. High-risk human papillomaviruses (HPV) are the causative agent of several cancers. In this study, we determined the prevalence and genotype distribution of HPV infection among Iranian patients with cervix lesions (CL) and breast cancer (BC). The study group consisted of postoperative tissues from patients diagnosed with cervix lesions and breast cancer. We analyzed 250 formalin-fixed, paraffin-embedded tissue blocks from 100 cervix lesions and 150 breast cancer samples. Verification of each cancer reported in a relative was sought through the pathology reports of the hospital records. Cervix lesions were collected from 100 patients with squamous metaplasia (SM, n=50), cervical intraepithelial neoplasia (CINI, n=18, CINII or III, n=8), and cervical carcinoma (CC, n=24). In this study we evaluated the prevalence of HPV by multiplex PCR in cervix lesions and breast cancer. For paraffin-embedded tissues, DNA extracted by the simple boiling method yielded higher proportions of successful gene amplification (99%) for b-actin gene. Overall prevalence of HPV infection was 6% in the SM group, 34.61% in the CIN group, 75% in the CC group, and 34.66% in the BC group. Furthermore, MY09/11 consensus PCR failed to detect 44 (55.69%) of all HPV infections and interestingly, the predominant genotype detected in all cancers was the oncogenic variant HPV16/18; about 34% of women aged 24 to 54 were infected with at least one type of HPV. Our results demonstrate that DNA derived from archival tissues that archived for less than 8 years could be used successfully for HPV genotyping by multiplex PCR. Infection with HPV was prevalent among Iranian women with CC and BC. The results indicate a likely causal role for high-risk HPV in CC and BC, and also offer the possibility of primary prevention of these cancers by vaccination against HPV in Iran.

  20. Hepatitis C virus genotypes and viral ribonucleic acid titers in Nigeria

    African Journals Online (AJOL)

    Background and Objectives: Hepatitis C virus (HCV) is a major cause of chronic liver disease, cirrhosis and hepatocellular cancer worldwide, with associated significant morbidity and mortality. It is estimated that 3% of the world population have HCV, and in Nigeria, prevalence rates of between 4.7-20% have been reported ...

  1. Ledipasvir-Sofosbuvir Plus Ribavirin in Treatment-Naive Patients With Hepatitis C Virus Genotype 3 Infection: An Open-Label Study.

    Science.gov (United States)

    Feld, Jordan J; Ramji, Alnoor; Shafran, Stephen D; Willems, Bernard; Marotta, Paul; Huchet, Emmanuelle; Vachon, Marie-Louise; Svarovskaia, Evguenia S; Huang, K C; Hyland, Robert H; Yun, Chohee; Massetto, Benedetta; Brainard, Diana M; McHutchison, John G; Tam, Edward; Bailey, Robert; Cooper, Curtis; Yoshida, Eric M; Greenbloom, Susan; Elkhashab, Magdy; Borgia, Sergio; Swain, Mark G

    2017-07-01

    Patients chronically infected with genotype 3 hepatitis C virus (HCV) have faster disease progression and are less responsive to current direct-acting antiviral regimens than patients infected with other genotypes. We conducted an open-label trial to evaluate the safety, tolerability, and efficacy of ledipasvir and sofosbuvir plus ribavirin in patients with genotype 3 HCV infection. We enrolled treatment-naive patients with and without compensated cirrhosis at 15 sites in Canada. All patients were treated with ledipasvir-sofosbuvir (90 mg and 400 mg) plus weight-based ribavirin for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). Secondary endpoints included evaluation of baseline and treatment-emergent drug resistance. Of the 111 patients enrolled, 105 (95%) had subtype 3a HCV and 39 (35%) had compensated cirrhosis. SVR12 was achieved by 99 of 111 patients (89%; 95% confidence interval, 82%-94%). Of the 39 patients with cirrhosis, 31 (79%) achieved SVR12, compared with 68 of 72 (94%) patients without cirrhosis. No treatment-emergent resistance mutations occurred in those who failed treatment. One patient discontinued treatment due to liver cancer and died 22 days after treatment discontinuation. The most common adverse events were fatigue (51%), headache (36%), and nausea (23%). In this multicenter trial involving treatment-naive patients with genotype 3 HCV, 12 weeks of ledipasvir-sofosbuvir provided a high level of SVR in those without cirrhosis. NCT02413593. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  2. Prevalence of Human Immunodeficiency Virus, Hepatitis C Virus, and Hepatitis B Virus Among Homeless and Nonhomeless United States Veterans.

    Science.gov (United States)

    Noska, Amanda J; Belperio, Pamela S; Loomis, Timothy P; O'Toole, Thomas P; Backus, Lisa I

    2017-07-15

    Veterans are disproportionately affected by human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV). Homeless veterans are at particularly high risk for HIV, HCV, and HBV due to a variety of overlapping risk factors, including high rates of mental health disorders and substance use disorders. The prevalence of HIV, HCV, and HBV among homeless veterans nationally is currently unknown. This study describes national testing rates and prevalence of HIV, HCV, and HBV among homeless veterans. Using data from the Department of Veterans Affairs (VA) Corporate Warehouse Data from 2015, we evaluated HIV, HCV, and HBV laboratory testing and infection confirmation rates and diagnoses on the Problem List for nonhomeless veterans and for veterans utilizing homeless services in 2015. Among 242740 homeless veterans in VA care in 2015, HIV, HCV, and HBV testing occurred in 63.8% (n = 154812), 78.1% (n = 189508), and 52.8% (n = 128262), respectively. The HIV population prevalence was 1.52% (3684/242740) among homeless veterans, compared with 0.44% (23797/5424685) among nonhomeless veterans. The HCV population prevalence among homeless veterans was 12.1% (29311/242740), compared with 2.7% (148079/5424685) among nonhomeless veterans, while the HBV population prevalence was 0.99% (2395/242740) for homeless veterans and 0.40% (21611/5424685) among nonhomeless veterans. To our knowledge this work represents the most comprehensive tested prevalence and population prevalence estimates of HIV, HCV, and HBV among homeless veterans nationally. The data demonstrate high prevalence of HIV, HCV, and HBV among homeless veterans, and reinforce the need for integrated healthcare services along with homeless programming. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  3. Psychiatric and substance use disorders in HIV/hepatitis C virus (HCV)-coinfected patients: does HCV clearance matter? [Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) HEPAVIH CO13 cohort].

    Science.gov (United States)

    Michel, L; Lions, C; Winnock, M; Lang, J-P; Loko, M-A; Rosenthal, E; Marchou, B; Valantin, M-A; Morlat, P; Roux, P; Sogni, P; Spire, B; Poizot-Martin, I; Lacombe, K; Lascoux-Combe, C; Duvivier, C; Neau, D; Dabis, F; Salmon-Ceron, D; Carrieri, M P

    2016-11-01

    The objective of this nested study was to assess the prevalence of psychiatric disorders in a sample of HIV/hepatitis C virus (HCV)-coinfected patients according to their HCV status. The nested cross-sectional study, untitled HEPAVIH-Psy survey, was performed in a subset of HIV/HCV-coinfected patients enrolled in the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) CO13 HEPAVIH cohort. Psychiatric disorders were screened for using the Mini International Neuropsychiatric Interview (MINI 5.0.0). Among the 286 patients enrolled in the study, 68 (24%) had never received HCV treatment, 87 (30%) were treatment nonresponders, 44 (15%) were currently being treated and 87 (30%) had a sustained virological response (SVR). Of the 286 patients enrolled, 121 patients (42%) screened positive for a psychiatric disorder other than suicidality and alcohol/drug abuse/dependence, 40 (14%) screened positive for alcohol abuse/dependence, 50 (18%) screened positive for drug abuse/dependence, 50 (17.5%) were receiving an antidepressant treatment and 69 (24%) were receiving an anxiolytic. Patients with an SVR did not significantly differ from the other groups in terms of psychiatric disorders. Patients receiving HCV treatment screened positive less often for an anxiety disorder. The highest rate of drug dependence/abuse was among HCV treatment-naïve patients. Psychiatric disorders were frequent in HIV/HCV-coinfected patients and their rates were comparable between groups, even for patients achieving an SVR. Our results emphasize the need for continuous assessment and care of coinfected patients, even after HCV clearance. Drug addiction remains an obstacle to access to HCV treatment. Despite the recent advent and continued development of directly acting antiviral agents (DAAs), it is still crucial to offer screening and comprehensive care for psychiatric and addictive disorders. © 2016 British HIV Association.

  4. Intrahepatic Vγ9Vδ2 T-cells from HCV-infected patients show an exhausted phenotype but can inhibit HCV replication.

    Science.gov (United States)

    Cimini, E; Bordoni, V; Sacchi, A; Visco-Comandini, U; Montalbano, M; Taibi, C; Casetti, R; Lalle, E; D'Offizi, G; Capobianchi, M R; Agrati, C

    2018-01-02

    Hepatitis C virus (HCV) persistence results from inefficiencies of both innate and adaptive immune responses to eradicate the infection. A functional impairment of circulating Vγ9Vδ2 T-cells was described but few data are available on Vγ9Vδ2 T-cells in the liver that, however, represents the battlefield in the HCV/host interaction. Aim of this work was to compare circulating and intrahepatic Vγ9Vδ2 T-cells in chronic HCV-infected patients (HCV pos ) and in HCV-negative (HCV neg ) subjects. Phenotypic and functional analysis was performed by flow cytometry. Anti-HCV activity was analyzed by using an in vitro autologous liver culture system. Independently from HCV infection, the liver was enriched of Vγ9Vδ2 T-cells expressing an effector/activated phenotype. In contrast, an enrichment of PD-1 expressing Vγ9Vδ2 T-cells was observed both in the peripheral blood and in the liver of HCV pos patients, probably due to a persistent antigenic stimulation. Moreover, a lower frequency of IFN-γ producing Vγ9Vδ2 T-cells was observed in the liver of HCV pos patients, suggesting a functional impairment in the cytokine production in HCV pos liver. Despite this hypo-responsiveness, intrahepatic Vγ9Vδ2 T-cells are able to exert an anti-HCV activity after specific stimulation. Altogether, our data show that HCV infection induced a dysregulation of intrahepatic Vγ9Vδ2 T cells that maintain their anti-HCV activity after specific stimulation. A study aimed to evaluate the mechanisms of the antiviral activity may be useful to identify new pathways able to improve Vγ9Vδ2 T-cells intrahepatic function during HCV infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Homozygosity for HLA group 2 alleles predicts treatment failure with interferon-α and ribavirin in chronic hepatitis C virus genotype 1 infection.

    Science.gov (United States)

    Collison, Meadhbh; Chin, Jun Liong; Abu Shanab, Ahmed; Mac Nicholas, Ross; Segurado, Ricardo; Coughlan, Suzie; Connell, Jeff; Carr, Michael J; Merriman, Raphael B; McCormick, P Aiden; Hall, William W

    2015-02-01

    Host genetic factors influence treatment responses to antiviral therapy in chronic hepatitis C virus (HCV) infection. We retrospectively investigated associations between host genetic markers and treatment-induced virologic responses to dual therapy with interferon-α and ribavirin in chronically infected HCV genotype 1 (g1)- and genotype 3 (g3)-infected individuals. A total of 171 patients (89 HCV g1 and 82 HCV g3 infected) were investigated for genetic markers influencing treatment-induced sustained virologic response (SVR). Overall, SVR was observed for 46/89 (52%) HCV g1- and 57/82 (70%) HCV g3-infected patients. Of the 4 interleukin 28B (IL28B) single-nucleotide polymorphisms (SNPs), rs12979860 was the host genetic marker most significantly associated with failure to achieve an SVR in HCV g1-infected individuals [P=3.83×10(-4); odds ratio (OR)=5.61; confidence interval (CI)=2.07-15.18] and gave a positive predictive value for treatment failure of 81.3% for minor homozygotes (TT). Using additive (P=3.54×10(-4)) and dominant models (P=3.83×10(-4)), a dosage effect of the T allele was observed, with the dominance term not significant for this SNP. Logistic regression showed an association between HLA-C1/C1 and rapid virologic response in HCV g1 infections with an OR relative to the heterozygote of 10.0 (95% CI: 1.6-62.5, P=0.014). HLA-C2 homozygosity was a significant predictor of nonresponse to treatment in HCV g1-infected individuals (P=0.023).

  6. Hepatitis B virus in Pakistan: A systematic review of prevalence, risk factors, awareness status and genotypes

    Directory of Open Access Journals (Sweden)

    Afzal Samia

    2011-03-01

    Full Text Available Abstract In Pakistan, there are estimated 7-9 million carriers of hepatitis B virus (HBV with a carrier rate of 3-5%. This article reviews the available literature about the prevalence, risk factors, awareness status and genotypes of the HBV in Pakistan by using key words; HBV prevalence, risk factors, awareness status and genotypes in Pakistani population in PubMed, PakMediNet, Directory of Open Access Journals (DOAJ and Google Scholar. One hundred and six different studies published from 1998 to 2010 were included in this study. Weighted mean and standard deviation were determined for each population group. The percentage of hepatitis B virus infection in general population was 4.3318% ± 1.644%, healthy blood donors (3.93% ± 1.58%, military recruits (4.276% ± 1.646%, healthcare persons (3.25% ± 1.202%, pregnant women (5.872% ± 4.984, prisoners (5.75% ± 0.212%, surgical patients (7.397% ± 2.012%, patients with cirrhosis (28.87% ± 11.90%, patients with HCC (22% ± 2.645%, patients with hepatitis (15.896% ± 14.824%, patients with liver diseases (27.54% ± 6.385%, multiple transfused patients (6.223% ± 2.121%, opthalmic patients (3.89% ± 1.004% and users of injectable drugs (14.95% ± 10.536%. Genotype D (63.71% is the most prevalent genotype in Pakistani population. Mass vaccination and awareness programs should be initiated on urgent basis especially in populations with HBV infection rates of more than 5%.

  7. Sex-specific effects of TLR9 promoter variants on spontaneous clearance of HCV infection.

    Science.gov (United States)

    Fischer, Janett; Weber, Alexander N R; Böhm, Stephan; Dickhöfer, Sabine; El Maadidi, Souhayla; Deichsel, Danilo; Knop, Viola; Klinker, Hartwig; Möller, Bernd; Rasenack, Jens; Wang, Lisa; Sharma, Manu; Hinrichsen, Holger; Spengler, Ulrich; Buggisch, Peter; Sarrazin, Christoph; Pawlita, Michael; Waterboer, Tim; Wiese, Manfred; Probst-Müller, Elsbeth; Malinverni, Raffaele; Bochud, Pierre-Yves; Gardiner, Clair; O'Farrelly, Cliona; Berg, Thomas

    2017-10-01

    As pathogen sensors, Toll-like receptors (TLR) play a role in the first defence line during HCV infection. However, the impact of the DNA sensor TLR9 on the natural course of HCV infection is unknown. To address this, TLR9 promoter polymorphisms (single nucleotide polymorphisms (SNPs)) rs187084 and rs5743836 were investigated for their effect on disease progression. Therefore, the TLR9 SNPs and the interferon lambda 4 ( IFNL4 ) rs12979860 were genotyped in chronically HCV type 1 infected (n=333), in patients who spontaneously cleared the infection (n=161), in the Swiss HCV cohort (n=1057) and the well-characterised German (n=305) and Irish (n=198) 'anti-D' cohorts. Functional analyses were done with promoter reporter constructs of human TLR9 in B cells and assessing TLR9 mRNA levels in whole blood of healthy volunteers. The TLR9 rs187084 C allele was associated with spontaneous virus clearance in women of the study cohort (OR=2.15 (95% CI 1.18 to 3.90) p=0.012), of the Swiss HCV cohort (OR=2.06 (95% CI 1.02 to 4.18) p=0.044) and in both 'anti-D' cohorts (German: OR=2.01 (95% CI 1.14 to 3.55) p=0.016; Irish: OR=1.93 (95% CI 1.10 to 3.68) p=0.047). Multivariate analysis in the combined study and Swiss HCV cohorts supported the results (OR=1.99 (95% CI 1.30 to 3.05) p=0.002). Functional analyses revealed higher transcriptional activities for both TLR9 variants and an association of the C allele of rs5743836 with allele-specific TLR9 mRNA regulation by oestrogens in women. TLR9 promoter SNPs are associated with the natural course of HCV infection and show higher transcriptional activities. Our results imply the DNA sensor TLR9 in natural immunity against the RNA virus, HCV. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  8. Hepatitis C and hepatitis B virus infection in different hemodialysis units in Belo Horizonte, Minas Gerais, Brazil

    Directory of Open Access Journals (Sweden)

    Busek Solange U

    2002-01-01

    Full Text Available The prevalence, virological and epidemilogical aspects of the hepatitis C virus (HCV and the hepatitis B virus (HBV infections vary among hemodialysis patients in different countries. Aiming at analyzing these aspects of HCV and HBV infections in hemodialysis patients in Belo Horizonte, MG, Brazil, we studied three hemodialysis units including 434 patients. Serology was used to detect anti-HCV and HBsAg. Reverse trancriptase nested polymerase chain reaction (RT-nested-PCR of the 5'-noncoding region was used to detect circulating HCV RNA and restriction fragment length polymorphism analysis for genotyping. Seroprevalence varied from 26.5% to 11.1% for hepatitis C and from 5.9% to 0% for hepatitis B. Risk factors observed for HBV and/or HCV infections were the number of patients per dialysis unit, duration of treatment, number of clinics attended, number of blood units transfused, and lower level scholarity. Alanine aminotransferase levels were altered with a higher frequency in HBV or HCV seropositive patients. Half of ten patients, negative for anti-HCV, had detectable viremia by RT-nested-PCR, indicating that this technique should be used to confirm infections in this group of patients. The HCV genotype 1 was the most frequently observed, followed by the genotype 2, but no correlation was detected between genotype and clinical or epidemiological data.

  9. Synthetic lipophilic antioxidant BO-653 suppresses HCV replication.

    Science.gov (United States)

    Yasui, Fumihiko; Sudoh, Masayuki; Arai, Masaaki; Kohara, Michinori

    2013-02-01

    The influence of the intracellular redox state on the hepatitis C virus (HCV) life cycle is poorly understood. This study demonstrated the anti-HCV activity of 2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran (BO-653), a synthetic lipophilic antioxidant, and examined whether BO-653's antioxidant activity is integral to its anti-HCV activity. The anti-HCV activity of BO-653 was investigated in HuH-7 cells bearing an HCV subgenomic replicon (FLR3-1 cells) and in HuH-7 cells infected persistently with HCV (RMT-tri cells). BO-653 inhibition of HCV replication was also compared with that of several hydrophilic and lipophilic antioxidants. BO-653 suppressed HCV replication in FLR3-1 and RMT-tri cells in a concentration-dependent manner. The lipophilic antioxidants had stronger anti-HCV activities than the hydrophilic antioxidants, and BO-653 displayed the strongest anti-HCV activity of all the antioxidants examined. Therefore, the anti-HCV activity of BO-653 was examined in chimeric mice harboring human hepatocytes infected with HCV. The combination treatment of BO-653 and polyethylene glycol-conjugated interferon-α (PEG-IFN) decreased serum HCV RNA titer more than that seen with PEG-IFN alone. These findings suggest that both the lipophilic property and the antioxidant activity of BO-653 play an important role in the inhibition of HCV replication. Copyright © 2012 Wiley Periodicals, Inc.

  10. Stability of hepatitis C virus (HCV) RNA levels among interferon-naïve HIV/HCV-coinfected individuals treated with combination antiretroviral therapy

    DEFF Research Database (Denmark)

    Grint, D; Peters, L; Reekie, J

    2013-01-01

    Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. High HCV RNA levels have been associated with poor treatment response. This study aimed to examine the natural history of HCV RNA in chronically HCV/HIV-coinfected individuals.......Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. High HCV RNA levels have been associated with poor treatment response. This study aimed to examine the natural history of HCV RNA in chronically HCV/HIV-coinfected individuals....

  11. Prevalence and prevalence trends of transfusion transmissible infections among blood donors at four chinese regional blood centers between 2000 and 2010

    Directory of Open Access Journals (Sweden)

    Li Changqing

    2012-08-01

    Full Text Available Abstract Background In China, high prevalence of HBV and HCV parallels with the growing epidemic of syphilis and HIV in the general population poses a great threat to blood safety. This study investigated the prevalence of serologic markers for transfusion transmissible infections (TTIs among four Chinese blood centers. Methods We examined whole blood donations collected from January 2000 through December 2010 at four Chinese blood centers. Post-donation testing of TTIs (HIV, HBV, HCV and syphilis were conducted using two different enzyme-linked immunosorbent assay kits for each seromarker. The prevalence of serologic markers for TTIs (% was calculated and additional analysis was conducted to examine donor characteristics associated with positive TTIs serology. Results Of the 4,366,283 donations, 60% were from first-time donors and 40% were from repeated donors. The overall prevalence of HIV, HBsAg, HCV and syphilis was 0.08%, 0.86%, 0.51% and 0.47%, respectively. The prevalence profile of TTIs varied among different blood centers and appeared at relatively high levels. Overall, the prevalence of HBsAg and HCV demonstrated a decline trend among four blood centers, while the prevalence of HIV and syphilis displayed three different trends: constantly steady, continually increasing and declining among different centers. Conclusions This study reflects the risk of TTIs has been greatly reduced in China, but blood transfusion remains an ongoing risk factor for the spread of blood-borne infections, and further work and improvements are needed to strengthen both safety and availability of blood in China.

  12. High Prevalence and Diversity of Hepatitis Viruses in Suspected Cases of Yellow Fever in the Democratic Republic of Congo.

    Science.gov (United States)

    Makiala-Mandanda, Sheila; Le Gal, Frédéric; Ngwaka-Matsung, Nadine; Ahuka-Mundeke, Steve; Onanga, Richard; Bivigou-Mboumba, Berthold; Pukuta-Simbu, Elisabeth; Gerber, Athenaïs; Abbate, Jessica L; Mwamba, Dieudonné; Berthet, Nicolas; Leroy, Eric Maurice; Muyembe-Tamfum, Jean-Jacques; Becquart, Pierre

    2017-05-01

    The majority of patients with acute febrile jaundice (>95%) identified through a yellow fever surveillance program in the Democratic Republic of Congo (DRC) test negative for antibodies against yellow fever virus. However, no etiological investigation has ever been carried out on these patients. Here, we tested for hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), and hepatitis E (HEV) viruses, all of which can cause acute febrile jaundice, in patients included in the yellow fever surveillance program in the DRC. On a total of 498 serum samples collected from suspected cases of yellow fever from January 2003 to January 2012, enzyme-linked immunosorbent assay (ELISA) techniques were used to screen for antibodies against HAV (IgM) and HEV (IgM) and for antigens and antibodies against HBV (HBsAg and anti-hepatitis B core protein [HBc] IgM, respectively), HCV, and HDV. Viral loads and genotypes were determined for HBV and HVD. Viral hepatitis serological markers were diagnosed in 218 (43.7%) patients. The seroprevalences were 16.7% for HAV, 24.6% for HBV, 2.3% for HCV, and 10.4% for HEV, and 26.1% of HBV-positive patients were also infected with HDV. Median viral loads were 4.19 × 10 5 IU/ml for HBV (range, 769 to 9.82 × 10 9 IU/ml) and 1.4 × 10 6 IU/ml for HDV (range, 3.1 × 10 2 to 2.9 × 10 8 IU/ml). Genotypes A, E, and D of HBV and genotype 1 of HDV were detected. These high hepatitis prevalence rates highlight the necessity to include screening for hepatitis viruses in the yellow fever surveillance program in the DRC. Copyright © 2017 Makiala-Mandanda et al.

  13. HBV reactivation in patients with HCV/HBV cirrhosis on treatment with direct-acting antivirals.

    Science.gov (United States)

    Calvaruso, V; Ferraro, D; Licata, A; Bavetta, M G; Petta, S; Bronte, F; Colomba, G; Craxì, A; Di Marco, V

    2018-01-01

    Anecdotal reports suggest that patients with chronic hepatitis C virus (HCV) hepatitis and overt or occult hepatitis B virus (HBV) coinfection may reactivate HBV when HCV is suppressed or cleared by direct-acting antivirals (DAAs). We assessed the prevalence of overt or previous HBV coinfection and the risk of HBV reactivation in patients with HCV cirrhosis treated with DAAs. This was a retrospective cohort of 104 consecutive patients with HCV cirrhosis treated with DAAs. Serum HCV-RNA and HBV-DNA were tested at weeks 4, 8 and 12 of DAAs therapy and at week 12 of follow-up. At the start of DAAs, eight patients (7.7%) were HBsAg positive/HBeAg negative with undetectable HBV-DNA and low levels of quantitative HBsAg (four on nucleos(t)ide analogues [NUCs] and four inactive carriers), 37 patients (35.6%) had markers of previous HBV infection (25 anti-HBc positive, 12 anti-HBc/anti-HBs positive) and 59 (56.7%) had no evidence of HBV infection. Sixty-seven patients (64.4%) were HCV-RNA negative at week 4 and 98 (94.2%) achieved sustained virological response. All four HBsAg-positive patients treated with NUCs remained HBV-DNA negative, but three of four untreated patients showed an increase in HBV-DNA of 2-3 log without a biochemical flare and achieved HBV-DNA suppression when given NUCs. During or after DAAs, by conventional assay, HBV-DNA remained not detectable in all 37 anti-HBc-positive patients but in three of them (8.1%) HBV-DNA became detectable with a highly sensitive PCR. HBV reactivation is likely to occur in untreated HBV/HCV-coinfected cirrhotic patients when they undergo HCV treatment with DAAs. Pre-emptive therapy with NUCs should be considered in this setting. Anti-HBc-positive patients rarely reactivate HBV without clinical or virological outcomes. © 2017 John Wiley & Sons Ltd.

  14. [HCV and HBV seropositivity in university students of the State of Nuevo Leòn, Mexico].

    Science.gov (United States)

    Flores-Castañeda, M S; García-Méndez, B L; Tijerina-Menchaca, R

    1996-01-01

    Viral hepatitis is a contagious disease. Patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV), may be either chronically symptomatic or asymptomatic, and suffer cirrhosis and high risk of hepatic carcinoma. Asymptomatic carriers of HBV surface antigen (HBs-Ag) or with anti-HCV antibodies are potentially infectious, and therefore a risk to public health. This work seeks to establish the frequency of seropositivity for HBs-Ag and anti-HCV antibodies in a population of 774 newly accepted students of the Medical School of the Autonomous University of Nuevo Leon, whose average age was 18 years. Second generation ELISA test were used to screen for HBs-Ag and anti-HCV antibodies. HBs-Ag was confirmed by a neutralization test and anti-HCV antibodies were confirmed by a RIBA test. Three sera were positive for HBs-Ag by ELISA and only one serum (0.13% of analyzed samples) was confirmed by the neutralization technique. On the other hand 12 sera were positive for anti-HCV antibodies by ELISA, and eight of these were confirmed by RIBA (1.03% of the analyzed samples). Intensive reactivity bands were found in two sera, and weak reactivity bands were found in six sera. ELISA screening for anti-HCV antibodies showed 0.5% of false positives. This study shows that the frequency of anti-HCV antibodies is 7.95% times higher than that found for HBs-Ag. All seropositive patients were asymptomatic and potentially infective. This demonstrates the need to routinely screen for HBs-Ag and anti-HCV antibodies to establish the prevalence of these diseases in our area.

  15. Human papilloma virus prevalence, genotype distribution, and pattern of infection in Thai women.

    Science.gov (United States)

    Suthipintawong, Cheepsumon; Siriaunkgul, Sumalee; Tungsinmunkong, Kobkul; Pientong, Chamsai; Ekalaksananan, Tipaya; Karalak, Anant; Kleebkaow, Pilaiwan; Vinyuvat, Songkhun; Triratanachat, Surang; Khunamornpong, Surapan; Chongsuwanich, Tuenjai

    2011-01-01

    The pattern of infection in cervical lesions with respect to HPV subtype has not been systematically studied in Thai women. The aim here was to determine HPV prevalence, genotype, and infection pattern in cervical lesions and to estimate the potential efficacy of an HPV prophylactic vaccine. Formalin-fixed paraffin-embedded cervical tissue blocks of 410 Thai patients from 8 institutes in 4 regions of Thailand (northern, southern, north-eastern, and central) were studied. The samples included 169 low grade squamous intraepithelial lesions (LSILs), 121 high grade squamous intraepithelial lesions (HSILs), and 120 squamous cell carcinomas (SCCs). HPV-DNA was amplified by PCR using consensus primers GP5+ and GP6+. The HPV genotype was then determined by reverse linear blot assay that included 37 HPV-specific 5'-amino-linked oligonucleotide probes. Patterns of infection were classified as single infection (one HPV type), double infection (two HPV types), and multiple infection (three or more HPV types). The mean age of the subjects was 42 years. The prevalence of HPV infection was 88.8%. The highest HPV prevalence was found in the southern region (97.1%) and the lowest in the central region (78.6%). HPV-DNA was detected in 84.6% of LSILs, 90.1% of HSILs, and 93.3% of SCCs. A total of 20 HPV genotypes were identified. The five most common high risk HPV were HPV16 (83.2%), HPV18 (59.3%), HPV58 (9.3%), HPV52 (4.1%), and HPV45 (3.8%). In double and multiple infection patterns, the most common genotypes were HPV16/18 (27.8%) and HPV11/16/18 (54.9%). HPV6 was found only in LSIL and never in combination with other subtypes. HPV11 was most common in LSIL. There is no difference of HPV type distribution in women from 4 regions of Thailand with prominent HPV16 and HPV18 in all cases. The bivalent and quadrivalent vaccines have the potential to prevent 48.6 % and 74.5% of cervical cancers in Thai women. The potential of cancer prevention would rise to 87.6% if other frequent HR

  16. An apparent lack of epidemiologic association between hepatitis C virus knowledge and the prevalence of hepatitis C infection in a national survey in Egypt.

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    Hiam Chemaitelly

    Full Text Available BACKGROUND: Egypt has by far the largest hepatitis C virus (HCV prevalence in the world with 14.7% of the population being antibody positive for HCV. The aim of this study was to examine the association between knowledge of HCV and HCV antibody positivity among the Egyptian population. METHODS: We characterized different measures of HCV knowledge and examined their associations with HCV prevalence, by analyzing a nationally representative database using standard epidemiologic methods. The database, the 2008 Egyptian Demographic and Health Survey, included demographic, health, and HCV biomarker information for a sample of over 12,000 individuals. RESULTS: Basic knowledge of HCV was found to be high, but multiple gaps were identified in the specific knowledge of HCV and its modes of transmission. There was no statistically significant difference in HCV prevalence between those who have heard of HCV infection and those who have not (14.4% vs. 15.9%, p>.05. Similar results were found for the other HCV knowledge measures including those specific to HCV modes of transmission and to the sources of information for HCV awareness. Logistic regression analyses did not demonstrate an association between HCV knowledge and HCV prevalence. CONCLUSIONS: Our results do not provide support for an effect of awareness on reducing the risk of HCV infection in Egypt. Public health messages directed at the lay public may not provide sufficient empowerment for individuals to avoid HCV infection, and should be complemented with prevention programs to promote and strengthen infection control in the settings of exposure, particularly in health care facilities.

  17. Understanding the molecular mechanism(s) of hepatitis C virus (HCV) induced interferon resistance.

    Science.gov (United States)

    Qashqari, Hanadi; Al-Mars, Amany; Chaudhary, Adeel; Abuzenadah, Adel; Damanhouri, Ghazi; Alqahtani, Mohammed; Mahmoud, Maged; El Sayed Zaki, Maysaa; Fatima, Kaneez; Qadri, Ishtiaq

    2013-10-01

    Hepatitis C virus (HCV) is one of the foremost causes of chronic liver disease affecting over 300 million globally. HCV contains a positive-stranded RNA of ~9600 nt and is surrounded by the 5' and 3'untranslated regions (UTR). The only successful treatment regimen includes interferon (IFN) and ribavirin. Like many other viruses, HCV has also evolved various mechanisms to circumvent the IFN response by blocking (1) downstream signaling actions via STAT1, STAT2, IRF9 and JAK-STAT pathways and (2) repertoire of IFN Stimulatory Genes (ISGs). Several studies have identified complex host demographic and genetic factors as well as viral genetic heterogeneity associated with outcomes of IFN therapy. The genetic predispositions of over 2000 ISGS may render the patients to become resistant, thus identification of such parameters within a subset of population are necessary for management corollary. The ability of various HCV genotypes to diminish IFN antiviral responses plays critical role in the establishment of chronic infection at the acute stage of infection, thus highlighting importance of the resistance in HCV treated groups. The recently defined role of viral protein such as C, E2, NS3/NS4 and NS5A proteins in inducing the IFN resistance are discussed in this article. How the viral and host genetic composition and epistatic connectivity among polymorphic genomic sites synchronizes the evolutionary IFN resistance trend remains under investigation. However, these signals may have the potential to be employed for accurate prediction of therapeutic outcomes. In this review article, we accentuate the significance of host and viral components in IFN resistance with the aim to determine the successful outcome in patients. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Epidemiological Profile and Risk Factors for Acquiring HBV and/or HCV in HIV-Infected Population Groups in Nepal.

    Science.gov (United States)

    Bhattarai, Manjula; Baniya, Jagat Bahadur; Aryal, Nirmal; Shrestha, Bimal; Rauniyar, Ramanuj; Adhikari, Anurag; Koirala, Pratik; Oli, Pardip Kumar; Pandit, Ram Deo; Stein, David A; Gupta, Birendra Prasad

    2018-01-01

    HBV and HCV infections are widespread among the HIV-infected individuals in Nepal. The goals of this study were to investigate the epidemiological profile and risk factors for acquiring HBV and/or HCV coinfection in disadvantaged HIV-positive population groups in Nepal. We conducted a retrospective study on blood samples from HIV-positive patients from the National Public Health Laboratory at Kathmandu to assay for HBsAg, HBeAg, and anti-HCV antibodies, HIV viral load, and CD4+ T cell count. Among 579 subjects, the prevalence of HIV-HBV, HIV-HCV, and HIV-HBV-HCV coinfections was 3.62%, 2.93%, and 0.34%, respectively. Multivariate regression analysis indicated that spouses of HIV-positive migrant labourers were at significant risk for coinfection with HBV infection, and an age of >40 years in HIV-infected individuals was identified as a significant risk factor for HCV coinfection. Overall our study indicates that disadvantaged population groups such as intravenous drug users, migrant workers and their spouses, female sex workers, and men who have sex with HIV-infected men are at a high and persistent risk of acquiring viral hepatitis. We conclude that Nepalese HIV patients should receive HBV and HCV diagnostic screening on a regular basis.

  19. Dynamic changes in HCV RNA levels and viral quasispecies in a patient with chronic hepatitis C after telaprevir-based treatment

    NARCIS (Netherlands)

    de Bruijne, Joep; Sullivan, James C.; Kieffer, Tara L.; Botfield, Martyn; Shames, Ben; Schinkel, Janke; Molenkamp, Richard; Weegink, Christine; Reesink, Henk

    2012-01-01

    Background: Telaprevir is a selective inhibitor of the hepatitis C virus NS3 center dot 4A serine protease. Treatment with telaprevir resulted in a rapid HCV-RNA decline in chronic hepatitis C genotype 1 patients. Objectives: To report the clinical and viral course of a patient treated with

  20. High Prevalence of Co-Infections by Invasive and Non-Invasive Chlamydia trachomatis Genotypes during the Lymphogranuloma Venereum Outbreak in Spain.

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    Mario Rodriguez-Dominguez

    Full Text Available The evolution of Chlamydia trachomatis is mainly driven by recombination events. This fact can be fuelled by the coincidence in several European regions of the high prevalence of non-invasive urogenital genotypes and lymphogranuloma venereum (LGV outbreaks. This scenario could modify the local epidemiology and favor the selection of new C. trachomatis variants. Quantifying the prevalence of co-infection could help to predict the potential risk in the selection of new variants with unpredictable results in pathogenesis or transmissibility. In the 2009-2013 period, 287 clinical samples with demonstrated presence of C. trachomatis were selected. They were divided in two groups. The first group was constituted by 137 samples with C. trachomatis of the LGV genotypes, and the second by the remaining 150 samples in which the presence of LGV genotypes was previously excluded. They were analyzed to detect the simultaneous presence of non-LGV genotypes based on pmpH and ompA genes. In the first group, co-infections were detected in 10.9% of the cases whereas in the second group the prevalence was 14.6%, which is the highest percentage ever described among European countries. Moreover, bioinformatic analyses suggested the presence among men who have sex with men of a pmpH-recombinant variant, similar to strains described in Seattle in 2002. This variant was the result of genetic exchange between genotypes belonging to LGV and members of G-genotype. Sequencing of other genes, phylogenetically related to pathotype, confirmed that the putative recombinant found in Madrid could have a common origin with the strains described in Seattle. Countries with a high prevalence of co-infections and high migration flows should enhance surveillance programs in at least their vulnerable population.

  1. High Prevalence of Co-Infections by Invasive and Non-Invasive Chlamydia trachomatis Genotypes during the Lymphogranuloma Venereum Outbreak in Spain.

    Science.gov (United States)

    Rodriguez-Dominguez, Mario; Gonzalez-Alba, Jose Maria; Puerta, Teresa; Menendez, Blanca; Sanchez-Diaz, Ana Maria; Canton, Rafael; del Romero, Jorge; Galan, Juan Carlos

    2015-01-01

    The evolution of Chlamydia trachomatis is mainly driven by recombination events. This fact can be fuelled by the coincidence in several European regions of the high prevalence of non-invasive urogenital genotypes and lymphogranuloma venereum (LGV) outbreaks. This scenario could modify the local epidemiology and favor the selection of new C. trachomatis variants. Quantifying the prevalence of co-infection could help to predict the potential risk in the selection of new variants with unpredictable results in pathogenesis or transmissibility. In the 2009-2013 period, 287 clinical samples with demonstrated presence of C. trachomatis were selected. They were divided in two groups. The first group was constituted by 137 samples with C. trachomatis of the LGV genotypes, and the second by the remaining 150 samples in which the presence of LGV genotypes was previously excluded. They were analyzed to detect the simultaneous presence of non-LGV genotypes based on pmpH and ompA genes. In the first group, co-infections were detected in 10.9% of the cases whereas in the second group the prevalence was 14.6%, which is the highest percentage ever described among European countries. Moreover, bioinformatic analyses suggested the presence among men who have sex with men of a pmpH-recombinant variant, similar to strains described in Seattle in 2002. This variant was the result of genetic exchange between genotypes belonging to LGV and members of G-genotype. Sequencing of other genes, phylogenetically related to pathotype, confirmed that the putative recombinant found in Madrid could have a common origin with the strains described in Seattle. Countries with a high prevalence of co-infections and high migration flows should enhance surveillance programs in at least their vulnerable population.

  2. Highly efficient infectious cell culture of three hepatitis C virus genotype 2b strains and sensitivity to lead protease, nonstructural protein 5A, and polymerase inhibitors

    DEFF Research Database (Denmark)

    Ramirez, Santseharay; Li, Yi-Ping; Jensen, Sanne B

    2014-01-01

    UNLABELLED: Hepatitis C virus (HCV) is a genetically diverse virus with multiple genotypes exhibiting remarkable differences, particularly in drug susceptibility. Drug and vaccine development will benefit from high-titer HCV cultures mimicking the complete viral life cycle, but such systems only ...

  3. PML tumor suppressor protein is required for HCV production

    International Nuclear Information System (INIS)

    Kuroki, Misao; Ariumi, Yasuo; Hijikata, Makoto; Ikeda, Masanori; Dansako, Hiromichi; Wakita, Takaji; Shimotohno, Kunitada; Kato, Nobuyuki

    2013-01-01

    Highlights: ► PML tumor suppressor protein is required for HCV production. ► PML is dispensable for HCV RNA replication. ► HCV could not alter formation of PML-NBs. ► INI1 and DDX5, PML-related proteins, are involved in HCV life cycle. -- Abstract: PML tumor suppressor protein, which forms discrete nuclear structures termed PML-nuclear bodies, has been associated with several cellular functions, including cell proliferation, apoptosis and antiviral defense. Recently, it was reported that the HCV core protein colocalizes with PML in PML-NBs and abrogates the PML function through interaction with PML. However, role(s) of PML in HCV life cycle is unknown. To test whether or not PML affects HCV life cycle, we examined the level of secreted HCV core and the infectivity of HCV in the culture supernatants as well as the level of HCV RNA in HuH-7-derived RSc cells, in which HCV-JFH1 can infect and efficiently replicate, stably expressing short hairpin RNA targeted to PML. In this context, the level of secreted HCV core and the infectivity in the supernatants from PML knockdown cells was remarkably reduced, whereas the level of HCV RNA in the PML knockdown cells was not significantly affected in spite of very effective knockdown of PML. In fact, we showed that PML is unrelated to HCV RNA replication using the subgenomic HCV-JFH1 replicon RNA, JRN/3-5B. Furthermore, the infectivity of HCV-like particle in the culture supernatants was significantly reduced in PML knockdown JRN/3-5B cells expressing core to NS2 coding region of HCV-JFH1 genome using the trans-packaging system. Finally, we also demonstrated that INI1 and DDX5, the PML-related proteins, are involved in HCV production. Taken together, these findings suggest that PML is required for HCV production.

  4. A longitudinal study investigating the prevalence of Staphylococcus aureus genotype B in seasonally communal dairy herds.

    Science.gov (United States)

    Voelk, V; Graber, H U; van den Borne, B H P; Sartori, C; Steiner, A; Bodmer, M; Haerdi-Landerer, M C

    2014-07-01

    Staphylococcus aureus is a major mastitis-causing pathogen. Various genotypes have been recently identified in Switzerland but Staph. aureus genotype B (GTB) was the only genotype associated with high within-herd prevalence. The risk of introducing this Staph. aureus genotype into a herd may be increased by frequent animal movements. This may also be the case when cows from different herds of origin are commingled and share their milking equipment for a limited period of time. The aim of the present study was to determine the prevalence of Staph. aureus GTB in seasonally communal dairy herds before and after a summer period when dairy farming is characterized by mixing cows from different herds of origin in 1 communal operation. In addition, the environment was investigated to identify potential Staph. aureus GTB reservoirs relevant for transmission of the disease. A total of 829 cows from 110 herds of origin in 9 communal operations were included in the study. Composite milk samples were collected from all cows during the first or second milking after arrival at the communal operation and again shortly before the end of the season. Swab samples from the environment, involved personnel, and herding dogs present were collected before the cows arrived. At the end of the season, sampling of personnel was repeated. All samples were analyzed for the presence of Staph. aureus GTB using an established quantitative PCR. At the beginning of the season, Staph. aureus GTB-positive cows were identified in 7 out of 9 communal operations and the within-communal operation prevalence ranged from 2.2 to 38.9%. At the second sampling, all communal operations were Staph. aureus GTB positive, showing within-communal operation prevalence from 1 to 72.1%. The between-herd of origin prevalence increased from 27.3 to 56.6% and the cow-level prevalence increased from 11.2% at the beginning of the season to 29.6% at the end of the season. On 3 different communal operations, Staph. aureus

  5. Molecular Signature in HCV-Positive Lymphomas

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    Valli De Re

    2012-01-01

    Full Text Available Hepatitis C virus (HCV is a positive, single-stranded RNA virus, which has been associated to different subtypes of B-cell non-Hodgkin lymphoma (B-NHL. Cumulative evidence suggests an HCV-related antigen driven process in the B-NHL development. The underlying molecular signature associated to HCV-related B-NHL has to date remained obscure. In this review, we discuss the recent developments in this field with a special mention to different sets of genes whose expression is associated with BCR coupled to Blys signaling which in turn was found to be linked to B-cell maturation stages and NF-κb transcription factor. Even if recent progress on HCV-B-NHL signature has been made, the precise relationship between HCV and lymphoma development and phenotype signature remain to be clarified.

  6. The Prevalence of Hepatitis C Virus (HCV) among Lichen Planus Patients and Its Clinical Pattern at the University of Abuja Teaching Hospital (U.A.T.H), Gwagwalada, Abuja, Nigeria

    Science.gov (United States)

    Bob, Ukonu Agwu; Augustine, Uhunmwangho

    2012-01-01

    Objective: The relationship between hepatitis C virus and Lichen Planus have been widely reported in the literature; although there are wide geographical variations in the reported prevalence of hepatitis C virus infection in patients with lichen planus. This study seeks to determine the prevalence of hepatitis C virus among lichen planus patients and its clinical morphological type in the University of Abuja Teaching Hospital, Gwagwalada Abuja, Nigeria. Materials/Methods: This study was conducted between January 2010 and December, 2011 at the out patients Dermatological unit of the department of medicine at the University of Abuja Teaching Hospital Gwagwalada Abuja, Nigeria. Consecutive patients who had body eruptions suspected to be lichen planus were recruited and histology done for confirmation. The control group included patients’ relations and some dermatology patients known to have low risk of hepatitis C virus infection and liver function tests done for both subjects and control after obtaining oral consent from them to participate in the study. Result: Anti- HCV antibodies were detected in nine cases (21.4%) and one case (3.3%) in the control group. This was statistically significant difference between the HCV antibody among the subject and control group (Plichen planus was the most frequent clinical type. Liver function test was not statistically significant among the subject and control group. Conclusion: Lichen planus and Hepatitis C virus appear to have a relationship and the prevalence rate was higher among the subject as compared to the control group in our environment. PMID:22980383

  7. Detection of HCV core antigen and its diagnostic significance

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    YANG Jie

    2013-02-01

    Full Text Available ObjectiveTo compare the abilities of the hepatitis C virus (HCV core antigen (cAg test and the HCV RNA assay for confirming anti-HCV presence in order to determine the clinical utility of the HCV-cAg as an alternative or confirmatory diagnostic tool. MethodsSerum samples collected from 158 patients diagnosed with HCV infection were subjected to the enzyme-linked immunosorbent assay-based HCV-cAg test. The optical density (OD measured values were used to calculate the ratio of specimen absorbance to the cutoff value (S/CO. Simultaneously, the serum samples were subjected to PCR-based nucleic acid amplification quantitative fluorescence detection of HCV RNA. ResultsNone of the serum samples had a S/CO value <1 for the HCV-cAg test (100% negative, but all of the samples had a S/CO value >5 (100% positive. The HCV-cAg test sensitivity was 87.05%, specificity was 76.67%, positive predictive value was 9653%, and negative predictive value was 44.23%. As the S/CO value gradually increased, the significantly higher positive coincident rate of the HCV RNA test decreased. The HCV RNA negative coincident rate was significantly higher than that of the HCV-cAg test. HCV-cAg S/CO values between 1 and 2 corresponded to an HCV RNA values between 1.0×103 copies/ml and 1.0×104 copies/ml. The highest S/CO value obtained was 1.992. ConclusionThe HCV-cAg test is comparable to the HCV RNA assay for diagnosing HCV infection.

  8. The evaluation of Recombinant Immunoblot assay (RIBA and HCV-RNA test results in patients with low titer Anti-HCV positivity

    Directory of Open Access Journals (Sweden)

    Berrin Uzun

    2014-12-01

    Full Text Available Objectives: Laboratory diagnosis of hepatitis C virus (HCV infection is based on the detection of anti-HCV antibodies by enzyme immunoassay (EIA or chemiluminescence immunoassay (CIA techniques. However, a consensus related to the problem of low titer (Serum/Cut-off; S/C= 1.0 anti-HCV antibodies is still lacking. The study attempts to evaluate the clinical status of the patients with low titer anti-HCV antibodies detected by third generation anti-HCV tests during February 2013- May 2014 retrospectively. Methods: Serum samples were studied by Advia Centaur XP autoanalyser (Bayer-Siemens, Germany for anti-HCV, and line immunoassay (Inno-LIATM HCV Score, İnnogenetics, Belgium for anti-HCV confirmatory test, Cobas AmpliPre/Cobas AMPLICOR HCV Test (Roche diagnostics, Switzerland for HCV RNA. Results: A total of 55.631 serum samples were studied, and 55 of them were anti-HCV positive of which with low antibody levels (sample/cutoff [S/CO]. S/CO values ranged from 1.15 to 6.15. Seventeen (31% of patients who have low antibody levels were defined as positive and 2 (4% patients were intermittent and 36 (65% patients were negative with line immunoassay. HCV-RNA was not detected in any of the samples. Conclusions: It is thought that antibody positivity must be verified in cases of recurrent reactivity when considering the cost-effectiveness of molecular tests. In the study was concluded that the use of molecular tests would be appropriate diagnosis, and the effectiveness of treatment if necessary after evaluation of patients with biochemical analysis. J Clin Exp Invest 2014; 5 (4: 553-556

  9. Cell culture system of a hepatitis C genotype 3a and 2a chimera

    DEFF Research Database (Denmark)

    2015-01-01

    A robust and genetically stable cell culture system for Hepatitis C Virus (HCV) genotype 3a is provided. A genotype 3a/2a (S52/JFH1) recombinant containing the structural genes (Core, E1, E2), p7 and NS2 of strain S52 was constructed and characterized in Huh7.5 cells. S52/JFH1 and J6/JFH viruses ...

  10. PML tumor suppressor protein is required for HCV production

    Energy Technology Data Exchange (ETDEWEB)

    Kuroki, Misao [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan); Research Fellow of the Japan Society for the Promotion of Science (Japan); Center for AIDS Research, Kumamoto University, Kumamoto 860-0811 (Japan); Ariumi, Yasuo, E-mail: ariumi@kumamoto-u.ac.jp [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan); Center for AIDS Research, Kumamoto University, Kumamoto 860-0811 (Japan); Hijikata, Makoto [Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606-8507 (Japan); Ikeda, Masanori; Dansako, Hiromichi [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan); Wakita, Takaji [Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640 (Japan); Shimotohno, Kunitada [Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba 272-8516 (Japan); Kato, Nobuyuki [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer PML tumor suppressor protein is required for HCV production. Black-Right-Pointing-Pointer PML is dispensable for HCV RNA replication. Black-Right-Pointing-Pointer HCV could not alter formation of PML-NBs. Black-Right-Pointing-Pointer INI1 and DDX5, PML-related proteins, are involved in HCV life cycle. -- Abstract: PML tumor suppressor protein, which forms discrete nuclear structures termed PML-nuclear bodies, has been associated with several cellular functions, including cell proliferation, apoptosis and antiviral defense. Recently, it was reported that the HCV core protein colocalizes with PML in PML-NBs and abrogates the PML function through interaction with PML. However, role(s) of PML in HCV life cycle is unknown. To test whether or not PML affects HCV life cycle, we examined the level of secreted HCV core and the infectivity of HCV in the culture supernatants as well as the level of HCV RNA in HuH-7-derived RSc cells, in which HCV-JFH1 can infect and efficiently replicate, stably expressing short hairpin RNA targeted to PML. In this context, the level of secreted HCV core and the infectivity in the supernatants from PML knockdown cells was remarkably reduced, whereas the level of HCV RNA in the PML knockdown cells was not significantly affected in spite of very effective knockdown of PML. In fact, we showed that PML is unrelated to HCV RNA replication using the subgenomic HCV-JFH1 replicon RNA, JRN/3-5B. Furthermore, the infectivity of HCV-like particle in the culture supernatants was significantly reduced in PML knockdown JRN/3-5B cells expressing core to NS2 coding region of HCV-JFH1 genome using the trans-packaging system. Finally, we also demonstrated that INI1 and DDX5, the PML-related proteins, are involved in HCV production. Taken together, these findings suggest that PML is required for HCV production.

  11. Depression in HIV and HCV co-infected patients: a systematic review and meta-analysis.

    Science.gov (United States)

    Fialho, Renata; Pereira, Marco; Rusted, Jennifer; Whale, Richard

    2017-10-01

    The aim of this study was to carry out a systematic review and meta-analysis of the differences in the prevalence of depression and presence of depressive symptoms between HIV/HCV co-infection, HIV mono-infection, and hepatitis C virus (HCV) mono-infection. A systematic electronic search of bibliographic databases was performed to locate articles published from the earliest available online until December 2014. Outcomes of depression were based on clinical interviews and validated self-reported measures of depression/depressive symptoms. Of the 188 records initially screened, 29 articles were included in the descriptive systematic review and six were included in the meta-analysis. The meta-analytic results indicated that, as measured by self-reported measures of depression, HIV/HCV co-infected patients were significantly more likely to report depressive symptoms than either HIV (SMD = .24, 95% CI: .03-.46, p = .02) or HCV mono-infected (SMD = .55, 95% CI: .17-.94, p = .005) patients. The variability of the results of the reviewed studies, largely dependent on the samples' characteristics and the methods of assessment of depression, suggests that a clear interpretation of how depression outcomes are affected by the presence of HIV/HCV co-infection is still needed. Failing to diagnose depression or to early screen depressive symptoms may have a significant impact on patients' overall functioning and compromise treatments' outcomes.

  12. Successful retreatment with grazoprevir and elbasvir for patients infected with hepatitis C virus genotype 1b, who discontinued prior treatment with NS5A inhibitor-including regimens due to adverse events.

    Science.gov (United States)

    Kanda, Tatsuo; Yasui, Shin; Nakamura, Masato; Nakamoto, Shingo; Takahashi, Koji; Wu, Shuang; Sasaki, Reina; Haga, Yuki; Ogasawara, Sadahisa; Saito, Tomoko; Kobayashi, Kazufumi; Kiyono, Soichiro; Ooka, Yoshihiko; Suzuki, Eiichiro; Chiba, Tetsuhiro; Maruyama, Hitoshi; Moriyama, Mitsuhiko; Kato, Naoya

    2018-03-23

    Sustained virologic response (SVR) by interferon and interferon-free treatment can results in the reduction of advanced liver fibrosis and the occurrence of hepatocellular carcinoma in patients infected with hepatitis C virus (HCV). Recent interferon-free treatment for HCV shortens the duration of treatment and leads to higher SVR rates, without any serious adverse events. However, it is important to retreat patients who have had treatment-failure with HCV non-structural protein 5A (NS5A) inhibitor-including regimens. Combination of sofosbuvir and ledipasvir only leads to approximately 100% SVR rates in HCV genotype (GT1b), NS5A inhibitor-naïve patients in Japan. This combination is not an indication for severe renal disease or heart disease, and these patients should be treated or retreated with a different regimen. Retreatment with HCV non-structural protein 3/4A inhibitor, grazoprevir, and HCV NS5A inhibitor, elbasvir, successfully eradicated HCV RNA in three patients with HCV genotype 1b infection who discontinued prior interferon-free treatments including HCV NS5A inhibitors due to adverse events within 2 weeks. Retreatment with the 12-week combination regimen of grazoprevir and elbasvir is effective for HCV GT1b patients who discontinue the HCV NS5A inhibitor-including regimens within 2 weeks. The treatment response may be related to the short duration of initial treatment, which did not produce treatment-emergent RASs.

  13. Rapid virological response assessment by Abbott RealTime hepatitis C virus assay for predicting sustained virological responses in patients with hepatitis C virus genotype 1 treated with pegylated-interferon and ribavirin

    Directory of Open Access Journals (Sweden)

    Pei-yuan Su

    2016-07-01

    Full Text Available The lower limits of virus detection of hepatitis C virus (HCV RNA detection assays are continuously improving. We aimed to assess the utility of more precise definition of 4th week viral load [rapid virological response (RVR] in predicting sustained virological response (SVR in HCV genotype 1 patients treated with pegylated-interferon (PEG-IFN and ribavirin. Clinical data of treatment-naïve HCV genotype 1 patients were retrospectively collected from 2009 to 2014. Patients were grouped according to 4th week viral load as follows: undetectable (n = 90 and detectable but not quantifiable (< 12 IU/mL, n = 27. All patients received PEG-IFNα-2a or -2b and ribavirin for 24 weeks. Serum HCV RNA levels were measured by Abbott RealTime (ART; Abbott Molecular, Abbott Park, IL, USA HCV assay. SVR was 95.5% and 63% in the undetectable group and < 12 IU/mL group of 4th week viral load, respectively. The between-group difference in SVR was significant (p < 0.001. We determined 4th week viral load was independently associated with SVR (odds ratio = 19.28; p = 0.002 and a good predictor of SVR [area under the curve (AUC = 0.775; p = 0.001]. ART HCV assays had a stronger SVR predictive value in HCV genotype 1 patients, indicating that only the undetectable group of 4th week viral load patients measured by ART HCV assay should be considered for shorter treatment time (24 weeks with PEG-IFN and ribavirin.

  14. Prevalence of Helicobacter pylori vacA Genotypes and cagA Gene in Dental Plaque of Asymptomatic Mexican Children

    Science.gov (United States)

    Mendoza-Cantú, Alejandra; Urbina-Ríos, Cynthia Sofía; García-Martínez, Martha Elena; Torre-Martínez, Hilda H. H.

    2017-01-01

    The variability in Helicobacter pylori vacA and cagA genes has been related to the progression of the gastrointestinal disease; also the presence of H. pylori in the oral cavity has been associated with periodontal disease in adults, but, in children without dyspeptic symptoms, little is known about this. We evaluated the prevalence of H. pylori and the presence of vacA/cagA genotypes in the oral cavity of Mexican children without dyspeptic symptoms. The gingival status was measured, and dental plaque samples (n = 100) were taken. 38% of children were positive for H. pylori 16S rRNA gene by qPCR. A significant association between H. pylori oral infection and gingival status was observed (P < 0.001). In 34.6% (9/26) of mild gingivitis cases, s1m2 genotype was found, while s1m1 was typed in 50% (3/6) of moderate gingivitis. The cagA prevalence among H. pylori-positive children was 80.8% (21/26), 83.3% (5/6), and 16.7% (1/6) of cases of mild gingivitis, moderate gingivitis, and nongingivitis, respectively (P < 0.001). The s1m1/cagA+ combinational genotype was the most detected in children with gingivitis. Our results suggest that the prevalence of H. pylori and detection of vacA/cagA genotypes-associated gastrointestinal disease in the oral cavity could be related to the progression of gingivitis in asymptomatic children. PMID:29226140

  15. Prevalence of Helicobacter pylori vacA Genotypes and cagA Gene in Dental Plaque of Asymptomatic Mexican Children

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    Alejandra Mendoza-Cantú

    2017-01-01

    Full Text Available The variability in Helicobacter pylori vacA and cagA genes has been related to the progression of the gastrointestinal disease; also the presence of H. pylori in the oral cavity has been associated with periodontal disease in adults, but, in children without dyspeptic symptoms, little is known about this. We evaluated the prevalence of H. pylori and the presence of vacA/cagA genotypes in the oral cavity of Mexican children without dyspeptic symptoms. The gingival status was measured, and dental plaque samples (n=100 were taken. 38% of children were positive for H. pylori 16S rRNA gene by qPCR. A significant association between H. pylori oral infection and gingival status was observed (P<0.001. In 34.6% (9/26 of mild gingivitis cases, s1m2 genotype was found, while s1m1 was typed in 50% (3/6 of moderate gingivitis. The cagA prevalence among H. pylori-positive children was 80.8% (21/26, 83.3% (5/6, and 16.7% (1/6 of cases of mild gingivitis, moderate gingivitis, and nongingivitis, respectively (P<0.001. The s1m1/cagA+ combinational genotype was the most detected in children with gingivitis. Our results suggest that the prevalence of H. pylori and detection of vacA/cagA genotypes-associated gastrointestinal disease in the oral cavity could be related to the progression of gingivitis in asymptomatic children.

  16. The geographic distribution patterns of HIV-, HCV- and co-infections among drug users in a national methadone maintenance treatment program in Southwest China.

    Science.gov (United States)

    Zhou, Yi-Biao; Liang, Song; Wang, Qi-Xing; Gong, Yu-Han; Nie, Shi-Jiao; Nan, Lei; Yang, Ai-Hui; Liao, Qiang; Song, Xiu-Xia; Jiang, Qing-Wu

    2014-03-10

    HIV-, HCV- and HIV/HCV co-infections among drug users have become a rapidly emerging global public health problem. In order to constrain the dual epidemics of HIV/AIDS and drug use, China has adopted a methadone maintenance treatment program (MMTP) since 2004. Studies of the geographic heterogeneity of HIV and HCV infections at a local scale are sparse, which has critical implications for future MMTP implementation and health policies covering both HIV and HCV prevention among drug users in China. This study aimed to characterize geographic patterns of HIV and HCV prevalence at the township level among drug users in a Yi Autonomous Prefecture, Southwest of China. Data on demographic and clinical characteristics of all clients in the 11 MMTP clinics of the Yi Autonomous Prefecture from March 2004 to December 2012 were collected. A GIS-based geographic analysis involving geographic autocorrelation analysis and geographic scan statistics were employed to identify the geographic distribution pattern of HIV-, HCV- and co-infections among drug users. A total of 6690 MMTP clients was analyzed. The prevalence of HIV-, HCV- and co-infections were 25.2%, 30.8%, and 10.9% respectively. There were significant global and local geographic autocorrelations for HIV-, HCV-, and co-infection. The Moran's I was 0.3015, 0.3449, and 0.3155, respectively (P geographic autocorrelation analysis and the geographic scan statistical analysis showed that HIV-, HCV-, and co-infections in the prefecture exhibited significant geographic clustering at the township level. The geographic distribution pattern of each infection group was different. HIV-, HCV-, and co-infections among drug users in the Yi Autonomous Prefecture all exhibited substantial geographic heterogeneity at the township level. The geographic distribution patterns of the three groups were different. These findings imply that it may be necessary to inform or invent site-specific intervention strategies to better devote currently

  17. Hepatitis C virus protease inhibitor-resistance mutations: our experience and review.

    Science.gov (United States)

    Wu, Shuang; Kanda, Tatsuo; Nakamoto, Shingo; Imazeki, Fumio; Yokosuka, Osamu

    2013-12-21

    Direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection are one of the major advances in its medical treatment. The HCV protease inhibitors boceprevir and telaprevir were the first approved DAAs in the United States, Europe, and Japan. When combined with peginterferon plus ribavirin, these agents increase sustained virologic response rates to 70%-80% in treatment-naïve patients and previous-treatment relapsers with chronic HCV genotype 1 infection. Without peginterferon plus ribavirin, DAA mono-therapies increased DAA-resistance mutations. Several new DAAs for HCV are now in clinical development and are likely to be approved in the near future. However, it has been reported that the use of these drugs also led to the emergence of DAA-resistance mutations in certain cases. Furthermore, these mutations exhibit cross-resistance to multiple drugs. The prevalence of DAA-resistance mutations in HCV-infected patients who were not treated with DAAs is unknown, and it is as yet uncertain whether such variants are sensitive to DAAs. We performed a population sequence analysis to assess the frequency of such variants in the sera of HCV genotype 1-infected patients not treated with HCV protease inhibitors. Here, we reviewed the literature on resistance variants of HCV protease inhibitors in treatment naïve patients with chronic HCV genotype 1, as well as our experience.

  18. HCV proteins and immunoglobulin variable gene (IgV) subfamilies in HCV-induced type II mixed cryoglobulinemia: a concurrent pathogenetic role.

    Science.gov (United States)

    Sautto, Giuseppe; Mancini, Nicasio; Solforosi, Laura; Diotti, Roberta A; Clementi, Massimo; Burioni, Roberto

    2012-01-01

    The association between hepatitis C virus (HCV) infection and type II mixed cryoglobulinemia (MCII) is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV) gene subfamilies frequently endowed with rheumatoid factor (RF) activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved.

  19. TNF-alpha 308 SNP Rs3091256 GG Genotype is Strongly Associated with Fibrosis in Patients with Chronic Hepatitis C

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    Özgür GÜNAL

    2017-12-01

    Full Text Available Objective: We aimed to review the influence of host genetic factors on the clinical course, treatment response as well as fibrosis progression in patients with viral hepatitis C genotype 1. Materials and Methods: Ninety-five patients with chronic hepatitis C virus (HCV infection and 97 controls were enrolled. The patients received pegylated interferon (Peg-IFN+ribavirin therapy for 48 weeks and were followed up for the next 48 weeks. Aspartat aminotransferase/platelet ratio (APRI was used to detect liver fibrosis DNA specimens were extracted from the peripheral blood mononuclear cells and the tumor necrosis factor-alpha (TNF-α 308 rs3091256 was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. Results: All patients included in the study were infected with HCV genotype 1. of the 95 HCV-positive patients, spontaneous viral clearence was observed in 25.5%, rapid viral response in 44.2%, early viral response in 91.8%, and sustained viral response was found in 73.3% of patients. The allele and genotype were not significant between patients and controls. There was no significant difference in virologic response as well. However, TNF-α-308 single nucleotide polymorphisms (SNP rs3091256 GG genotype was strongly associated with fibrosis and alanine aminotransferase (ALT levels (p=0.006 and p=0.017, respectively. Conclusion: TNF-α-308 polymorphisms may reveal different results among countries. Patients having SNP rs3091256 GG are prone to have higher ALT levels and fibrosis score but have better treatment outcome.

  20. Prevalence of hepatitis C infection in Iranian hemodialysis patients: An updated systematic review and meta-analysis

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    Nahid Ramezan Ghorbani

    2017-01-01

    Full Text Available Background: Hepatitis C virus (HCV is a major cause of liver disease and a potential cause of substantial morbidity and mortality. This study aims to provide a comprehensive evidence on HCV Infection in Iranian hemodialysis (HD patients we conducted a systematic review. Materials and Methods: In this systematic review and meta-analysis, through a comprehensive search of literature until January of 2016, we estimated the pooled prevalence of hepatitis C infection in Iranian HD patients. Using Medical Subject Headings terms, Emtree, and related equal Persian key words for Iranian databases and also international databases of PubMed and NLM Gateway (for MEDLINE, and SCOPUS. Interest outcome of HCV infection prevalence was confirmed based on positive hepatitis B surface antigen of blood samples. Random effect meta-analysis was used to estimate pooled prevalence of HCV infection in Iranian HD patients, date and language, HD patients, in adult HD patients, Institute of Scientific Information, Iran-doc, irrespective of age, living in Iran. Searches run through main domestic databanks of Iran-Medex, renal transplantation, Scientific Information Database, the relevant literature-searched concentrating on HCV infection. Results: Through searching steps, 305 publications were found from them following the excluding duplicates and overlapping studies 54 studies relevant to HCV prevalence in Iranian HD zcxw patients, with number of 23921 participants, remained in our analyses. The overall results of test of heterogeneity demonstrate sever heterogeneity between reported prevalence (I2 = 96.62%, Chi-square = 1566, P < 0.001. Due to sever heterogeneity results of random effect meta-analysis showed that the estimated pooled prevalence was 11% (95% confidence interval [CI] =10%–13%. The pooled prevalence base on polymerase-chain reaction, recombinant immunoblot assay, and enzyme-Linked Immunosorbant Antibody method were 11% (95% CI = 6%–15%, 9% (95% CI = 5

  1. HCV subtype characterization among injection drug users: implication for a crucial role of Zhenjiang in HCV transmission in China.

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    Chiyu Zhang

    Full Text Available BACKGROUND: HCV transmission is closely associated with drug-trafficking routes in China. However, the transmission route of HCV in Eastern China remains unclear. Here, we investigate the role of Zhenjiang city of Jiangsu province, an important transportation hub linking Shanghai with other regions of China, in HCV transmission. METHODOLOGY/PRINCIPAL FINDINGS: A total of 141 whole blood samples were collected from injection drug users (IDUs in Zhenjiang and then tested for HCV infection. Of them, 115 HCV positive plasmas were subjected to RNA extraction, RT-PCR amplification, and sequencing. The subtype characterization and the evolutionary origin of HCV strains circulating in Zhenjiang were determined using polygenetic or phylogeographic analyses. Seven HCV subtypes 1b, 2a, 3a, 3b, 6a, 6e and 6n were detected among Zhenjiang IDUs, showing a complex HCV epidemic. The most predominant subtypes were 3a (38% and 1b (26.8%. Among these subtypes, subtypes 3b, 6n and 6e originated from Southwestern China (i.e., Yunnan and/or Guangxi, subtypes 2a and 6a from Southern China (i.e., Guangdong, subtype 1b from Central (i.e., Henan and Northwestern (i.e., Xinjiang China, and subtype 3a from Southwestern (i.e., Yunnan and Northwestern (i.e., Xinjiang China. From Zhenjiang, subtypes 1b and 2a were further spread to Eastern (i.e., Shanghai and Northern (i.e., Beijing China, respectively. CONCLUSIONS/SIGNIFICANCE: The mixing of seven HCV subtypes in Zhenjiang from all quarters of China indicates that as an important middle station, Zhenjiang plays a crucial role in HCV transmission, just as it is important in population migration between other regions of China and Eastern China.

  2. Prevalence of the Human Papilloma Virus (HPV genotypes in south-central Sicily: a comparative study between 2003 and 2011

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    Liborio Bellomo

    2013-08-01

    Full Text Available This issue is about our Human Papilloma Virus (HPV DNA test. We have examined two cohorts of patients from south-central Sicily, who were tested for HPV -DNA derived from cervical sampling, respectively in 2003 and 2011. In 2003, the most represented genotypes were: 31, 16. Instead, in 2011 there was a higher prevalence for genotypes: 42, 16. It is remarkable to note that the 35 genotype, noticed in 2003, has never been found in the second most recent group.

  3. Non-genotype-specific role of the hepatitis C virus 5' untranslated region in virus production and in inhibition by interferon

    DEFF Research Database (Denmark)

    Li, Yi-Ping; Ramirez, Santseharay; Gottwein, Judith M

    2011-01-01

    The 5' untranslated region (5'UTR) of hepatitis C virus (HCV) is structured into four domains (I-IV) with numerous genotype-specific nucleotides. It is unknown whether the polymorphisms confer genotype-specific functions to the 5'UTR. Using viable JFH1-based Core-NS2 recombinants, we developed...

  4. Prevalence, sociodemographic characteristics and risk factors for hepatitis C infection among pregnant women in Calabar municipality, Nigeria.

    Science.gov (United States)

    Mboto, Clement Ibi; Andy, Iniobong Ebenge; Eni, Ogban Ibor; Jewell, Andrew Paul

    2010-01-01

    The epidemiology and risk factors for hepatitis C virus (HCV) infection in developing countries where intravenous drug use (IDU) is uncommon its poorly understood. This study therefore aims to determine the prevalence of HCV and its associated risk factors among pregnant women in Calabar municipality. A total of 506 out of 716 antenatal care (ANC) patients seen at the General Hospital, Mary Slessor Avenue, Calabar between August and November 2005 and the University of Calabar Teaching Hospital (UCTH) between October and November 2005 were evaluated for their HCV status using the One Step HCV Test kit (Binomial diagnostics, UK), with reference to the subjects' demographic and behavioural risk factors. HCV prevalence was determined to be 0.4% (2/506) and was only seen in women aged 38 years and over. Histories of blood transfusion, surgery, involvement in polygamous marriage, sharing of a toothbrush and female circumcision were all non-significant risk factors for the infecion. This study reveals a low HCV prevalence among pregnant women in Calabar municipality with no identifiable risk factor. The study calls for a re-evaluation of the transmission modes of HCV especially in developing countries where intravenous drug use is rare.

  5. HCV Proteins and Immunoglobulin Variable Gene (IgV Subfamilies in HCV-Induced Type II Mixed Cryoglobulinemia: A Concurrent Pathogenetic Role

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    Giuseppe Sautto

    2012-01-01

    Full Text Available The association between hepatitis C virus (HCV infection and type II mixed cryoglobulinemia (MCII is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV gene subfamilies frequently endowed with rheumatoid factor (RF activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved.

  6. Recombinant HCV variants with NS5A from genotypes 1-7 have different sensitivities to an NS5A inhibitor but not interferon-a

    DEFF Research Database (Denmark)

    Scheel, Troels K H; Gottwein, Judith M; Mikkelsen, Lotte S

    2011-01-01

    Heterogeneity in the hepatitis C virus (HCV) protein NS5A influences its sensitivity to interferon-based therapy. Furthermore, NS5A is an important target for development of HCV-specific inhibitors. We aimed to develop recombinant infectious cell culture systems that express NS5A from isolates...

  7. Effect of abacavir on sustained virologic response to HCV treatment in HIV/HCV co-infected patients, Cohere in Eurocoord

    DEFF Research Database (Denmark)

    Smit, Colette; Arends, Joop; Peters, Lars

    2015-01-01

    BACKGROUND: Contradicting results on the effect of abacavir (ABC) on hepatitis C virus (HCV) treatment responses in HIV/HCV co-infected patients have been reported. We evaluated the influence of ABC on the response to pegylated interferon (pegIFN) and ribavirin (RBV)-containing HCV treatment in H...

  8. Highly Efficient JFH1-Based Cell-Culture System for Hepatitis C Virus Genotype 5a: Failure of Homologous Neutralizing-Antibody Treatment to Control Infection

    DEFF Research Database (Denmark)

    Jensen, Tanja B; Gottwein, Judith Margarete; Scheel, Troels Kasper Høyer

    2008-01-01

    of recovered genomes and reverse-genetic studies. Receptor blockage was performed with anti-CD81 and anti-SR-BI. For neutralization experiments, SA13/JFH1 or JFH1-based viruses of other genotypes were incubated with patient sera. Results. @nbsp; SA13/JFH1 with NS2 and NS3 mutations yielded infectivity titers......Background. @nbsp; Recently, a hepatitis C virus (HCV) cell-culture system was developed that employed strain JFH1 (genotype 2a), and JFH1-based intra- and intergenotypic recombinants now permit functional studies of the structural genes (Core, E1, and E2), p7, and NS2 of genotypes 1-4. The goal...... was to adapt the system to employ genotype 5. Methods. @nbsp; Huh7.5 cells infected with SA13/JFH1, containing Core-NS2 of strain SA13 (genotype 5a), were monitored for Core expression and for supernatant infectivity and HCV-RNA titers. Adaptive mutations of SA13/JFH1 were identified by sequence analysis...

  9. Identification of Variants of Hepatitis C Virus (HCV Entry Factors in Patients Highly Exposed to HCV but Remaining Uninfected: An ANRS Case-Control Study.

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    Baptiste Fouquet

    Full Text Available Hepatitis C virus (HCV causes persistent infection in 75% of cases and is a major public health problem worldwide. More than 92% of intravenous drug users (IDU infected by human immunodeficiency virus type 1 (HIV-1 are seropositive for HCV, and it is conceivable that some HIV-1-infected IDU who remain uninfected by HCV may be genetically resistant.Here we conducted a case-control study to identify mutations in HCV entry coreceptors in HIV-infected IDU who remained uninfected by HCV. We recruited 138 patients, comprising 22 HIV+ HCV- case IDU and 116 HIV+ HCV+ control IDU. We focused on coreceptors in which point mutations are known to abolish HCV infectivity in vitro. Our previous study of the Claudin-1 gene revealed no specific variants in the same case population. Here we performed direct genomic sequencing of the Claudin-6, Claudin-9, Occludin and Scavenger receptor-B1 (SCARB1 gene coding regions. Most HIV+ HCV- IDU had no mutations in HCV coreceptors. However, two HIV+ HCV- patients harbored a total of four specific mutations/variants of HCV entry factors that were not found in the HIV+ HCV+ controls. One case patient harbored heterozygous variants of both Claudin-6 and Occludin, and the other case patient harbored two heterozygous variants of SCARB1. This suggests that HCV resistance might involve complex genetic events and factors other than coreceptors, a situation similar to that reported for HIV-1 resistance.

  10. Prevalence of genotypic HIV-1 drug resistance in Thailand, 2002

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    Watitpun Chotip

    2003-03-01

    Full Text Available Abstract Background The prices of reverse transcriptase (RT inhibitors in Thailand have been reduced since December 1, 2001. It is expected that reduction in the price of these inhibitors may influence the drug resistance mutation pattern of HIV-1 among infected people. This study reports the frequency of HIV-1 genetic mutation associated with drug resistance in antiretroviral-treated patients from Thailand. Methods Genotypic resistance testing was performed on samples collected in 2002 from 88 HIV-1 infected individuals. Automated DNA sequencing was used to genotype the HIV-1 polymerase gene isolated from patients' plasma. Results Resistance to protease inhibitors, nucleoside and non-nucleoside reverse transcriptase inhibitors were found in 10 (12%, 42 (48% and 19 (21% patients, respectively. The most common drug resistance mutations in the protease gene were at codon 82 (8%, 90 (7% and 54 (6%, whereas resistant mutations at codon 215 (45%, 67 (40%, 41 (38% and 184 (27% were commonly found in the RT gene. This finding indicates that genotypic resistance to nucleoside reverse transcriptase inhibitors was prevalent in 2002. The frequency of resistant mutations corresponding to non-nucleoside reverse transcriptase inhibitors was three times higher-, while resistant mutation corresponding to protease inhibitors was two times lower than those frequencies determined in 2001. Conclusion This study shows that the frequencies of RT inhibitor resistance mutations have been increased after the reduction in the price of RT inhibitors since December 2001. We believe that this was an important factor that influenced the mutation patterns of HIV-1 protease and RT genes in Thailand.

  11. Robust full-length hepatitis C virus genotype 2a and 2b infectious cultures using mutations identified by a systematic approach applicable to patient strains

    DEFF Research Database (Denmark)

    Li, Yi-Ping; Ramirez, Santseharay; Gottwein, Judith M

    2012-01-01

    Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases worldwide, but treatment options are limited. Basic HCV research required for vaccine and drug development has been hampered by inability to culture patient isolates, and to date only the JFH1 (genotype 2a) recombinant...... represents an important advance, and the approach used might permit culture development of other isolates, with implications for improved individualized treatments of HCV patients and for development of broadly efficient vaccines....

  12. [Comparison of eight screening tests for ant-HCV antibody].

    Science.gov (United States)

    Deguchi, Matsuo; Kagita, Masanori; Yamashita, Naoko; Nakano, Takasi; Tahara, Kazuko; Asari, Seishi; Iwatani, Yoshinori

    2002-09-01

    We compared eight HCV screening tests for detection of anti-HCV antibody; Ortho Quick Chaser HCV Ab (QC), Ortho HCV Ab ELISA III (ELISA), Ortho HVC Ab PA test III (PA), Lumipulse II Ortho HCV (LUMI), IMx HCV.DAINAPACKII (IMx), ARCHITECT HCV (ARCH), Immucheck.F-HCV C50 Ab (Immu), RANREAM HCV Ab Ex II (RAN). Sera from six hundred patients were examined by these eight screening tests. The positive rates of the eight screening tests were from 9.0% to 13.2%. Forty-five sera showed discrepant results between the eight screening tests, and about half of them showed weak positive reaction and/or false positive. Twenty-five of the forty-five sera were negative for ant-HCV antibody in the CHIRON RIBA III confirmatory test, and forty-four of them were negative for HCV-RNA in the PCR method. The agreement rates between the two reagents were from 95.5% to 99.2%, but were not always high between the two reagents that used similar antigen. The specificities and sensitivities evaluated by using the RIBA III confirmatory test were excellent in ELISA, LUMI, IMx, ARCH and Immu. Three BBI seroconversion panels were used to compare the positive readings in the initial stage of HCV infection by eight screening tests. ELISA and ARCH showed the earliest positive readings, and then IMx, LUMI = RAN, PA, QC and Immu in this order. These findings indicate that ELISA and ARCH were the most excellent in the sensitivity, specificity and early diagnosis of HCV infection. However, we must pay attention to the weak positive reaction in the screening tests, because there is a possibility of "false positive".

  13. Proteasome- and Ethanol-Dependent Regulation of HCV-Infection Pathogenesis

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    Natalia A. Osna

    2014-09-01

    Full Text Available This paper reviews the role of the catabolism of HCV and signaling proteins in HCV protection and the involvement of ethanol in HCV-proteasome interactions. HCV specifically infects hepatocytes, and intracellularly expressed HCV proteins generate oxidative stress, which is further exacerbated by heavy drinking. The proteasome is the principal proteolytic system in cells, and its activity is sensitive to the level of cellular oxidative stress. Not only host proteins, but some HCV proteins are degraded by the proteasome, which, in turn, controls HCV propagation and is crucial for the elimination of the virus. Ubiquitylation of HCV proteins usually leads to the prevention of HCV propagation, while accumulation of undegraded viral proteins in the nuclear compartment exacerbates infection pathogenesis. Proteasome activity also regulates both innate and adaptive immunity in HCV-infected cells. In addition, the proteasome/immunoproteasome is activated by interferons, which also induce “early” and “late” interferon-sensitive genes (ISGs with anti-viral properties. Cleaving viral proteins to peptides in professional immune antigen presenting cells and infected (“target” hepatocytes that express the MHC class I-antigenic peptide complex, the proteasome regulates the clearance of infected hepatocytes by the immune system. Alcohol exposure prevents peptide cleavage by generating metabolites that impair proteasome activity, thereby providing escape mechanisms that interfere with efficient viral clearance to promote the persistence of HCV-infection.

  14. Hypervariable region 1 differentially impacts viability of hepatitis C virus strains of genotypes 1 to 6 and impairs virus neutralization

    DEFF Research Database (Denmark)

    Prentoe, Jannick; Jensen, Tanja B; Meuleman, Philip

    2011-01-01

    Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) E2 envelope glycoprotein has been implicated in virus neutralization and persistence. We deleted HVR1 from JFH1-based HCV recombinants expressing Core/E1/E2/p7/NS2 of genotypes 1 to 6, previously found to grow efficiently in human hepatoma...... genetics studies revealed adaptive envelope mutations that rescued the infectivity of 1a(ΔHVR1), 1b(ΔHVR1), 2b(ΔHVR1), and 3a(ΔHVR1) recombinants. Thus, HVR1 might have distinct functional roles for different HCV isolates. Ultracentrifugation studies showed that deletion of HVR1 did not alter HCV RNA...... density distribution, whereas infectious particle density changed from a range of 1.0 to 1.1 g/ml to a single peak at ∼1.1 g/ml, suggesting that HVR1 was critical for low-density HCV particle infectivity. Using chronic-phase HCV patient sera, we found three distinct neutralization profiles...

  15. Hypervariable region 1 differentially impacts viability of hepatitis C virus strains of genotypes 1 to 6 and impairs virus neutralization

    DEFF Research Database (Denmark)

    Prentø, Jannick Cornelius; Jensen, Tanja Bertelsen; Meuleman, Philip

    2011-01-01

    Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) E2 envelope glycoprotein has been implicated in virus neutralization and persistence. We deleted HVR1 from JFH1-based HCV recombinants expressing Core/E1/E2/p7/NS2 of genotypes 1 to 6, previously found to grow efficiently in human hepatoma...... genetics studies revealed adaptive envelope mutations that rescued the infectivity of 1a(¿HVR1), 1b(¿HVR1), 2b(¿HVR1), and 3a(¿HVR1) recombinants. Thus, HVR1 might have distinct functional roles for different HCV isolates. Ultracentrifugation studies showed that deletion of HVR1 did not alter HCV RNA...... density distribution, whereas infectious particle density changed from a range of 1.0 to 1.1 g/ml to a single peak at ~1.1 g/ml, suggesting that HVR1 was critical for low-density HCV particle infectivity. Using chronic-phase HCV patient sera, we found three distinct neutralization profiles...

  16. Prevalence of hepatitis C virus infection among hemodialysis patients in the Middle-East: A systematic review and meta-analysis.

    Science.gov (United States)

    Ashkani-Esfahani, Soheil; Alavian, Seyed Moayed; Salehi-Marzijarani, Mohammad

    2017-01-07

    To determine hepatitis C virus (HCV) infection prevalence in each country of the Middle-East and the overall prevalence of the region. In this systematic review, we gathered all documents related to HCV infection prevalence among hemodialysis patients in 17 middle-east countries from April 2006 to March 2016. We selected only cross-sectional studies that had proper sampling and measurement methods as well as a valid statistical analysis. After screening of 7311 documents, 56 studies were selected reporting the prevalence of HCV infection among hemodialysis patients from 10 countries of the region. Seven countries including United Arab Emirates, Afghanistan, Qatar, Bahrain, Kuwait, Oman, Israel, and Cyprus did not have any relevant document; thus, their latest reports were just mentioned. We performed the meta-analysis and determined the prevalence rates for each country as well as the whole region. The overall HCV infection prevalence among hemodialysis patients in the region was reported to be 25.3%; Egypt and Syria had the highest reported rates while Iran and Lebanon had the lowest. Further investigations are still needed to provide more reliable databases, find main risk factors, and to improve diagnosis and treatment plans, particularly in higher prevalent countries. Controlling the prevalence and improving the management methods of HCV infection among hemodialysis patients are of a great concern in the Middle-East region.

  17. Association between insulin resistance and sustained virologic response in hepatitis C treatment, genotypes 1 versus 2 and 3: systematic literature review and meta-analysis.

    Science.gov (United States)

    Laurito, Marcela Pezzoto; Parise, Edison Roberto

    2013-01-01

    Controversial results have been found in literature for the association between insulin resistance and sustained virologic response to standard chronic hepatitis C treatment. This study aims to provide a systematic literature review with meta-analysis, in order to evaluate if insulin resistance interferes with sustained virologic response in patients infected by the HCV genotype 1 versus HCV genotypes 2 and 3, undergoing treatment with interferon and ribavirin or pegylated interferon and ribavarin. Systematic search was performed on main electronic databases until May 2012. Primary outcome was sustained virologic response, defined as undetectable levels of HCV-RNA six months after the end of treatment. Meta-analytic measure was estimated using Dersimonian and Laird's method, using Stata software. Thirteen studies involving 2238 infected patients were included. There was a statistically significant association between insulin resistance and lower sustained virologic response rate, and this difference occurred in HCV genotype G1 (OR: 2.23; 95% CI: 1.59-3.13) and G2/G3 (OR: 4.45; 95% CI: 1.59-12.49). In addition, a difference was seen in the cut-offs used for defining insulin resistance by Homeostasis Model Assessment of Insulin Resistance. To minimize this limitation, sub-analysis that excluded the studies that did not use 2 as a cut-off value was performed and the results still demonstrated association between insulin resistance and sustained virologic response, for both genotypic groups. This meta-analysis provides evidence that elevated Homeostasis Model Assessment of Insulin Resistance is associated with a lower sustained virologic response rate in patients with hepatitis C treated with interferon and ribavirin or pegylated interferon and ribavarin, regardless of their genotype. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

  18. One or two serological assay testing strategy for diagnosis of HBV and HCV infection? The use of predictive modelling.

    Science.gov (United States)

    Parry, John V; Easterbrook, Philippa; Sands, Anita R

    2017-11-01

    Initial serological testing for chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is conducted using either rapid diagnostic tests (RDT) or laboratory-based enzyme immunoassays (EIA)s for detection of hepatitis B surface antigen (HBsAg) or antibodies to HCV (anti-HCV), typically on serum or plasma specimens and, for certain RDTs, capillary whole blood. WHO recommends the use of standardized testing strategies - defined as a sequence of one or more assays to maximize testing accuracy while simplifying the testing process and ideally minimizing cost. Our objective was to examine the diagnostic outcomes of a one- versus two-assay serological testing strategy. These data were used to inform recommendations in the 2017 WHO Guidelines on hepatitis B and C testing. Few published studies have compared diagnostic outcomes for one-assay versus two-assay serological testing strategies for HBsAg and anti-HCV. Therefore, the principles of Bayesian statistics were used to conduct a modelling exercise to examine the outcomes of a one-assay versus two-assay testing strategy when applied to a hypothetical population of 10,000 individuals. The resulting model examined the diagnostic outcomes (true and false positive diagnoses; true and false negative diagnoses; positive and negative predictive values as a function of prevalence; and total tests required) for both one-assay and two-assay testing strategies. The performance characteristics assumed for assays used within the testing strategies were informed by WHO prequalification assessment findings and systematic reviews for diagnostic accuracy studies. Each of the presumptive testing strategies (one-assay or two-assay) was modelled at varying prevalences of HBsAg (10%, 2% and 0.4%) and of anti-HCV (40%, 10%, 2% and 0.4%), aimed at representing the range of testing populations typically encountered in WHO Member States. When the two-assay testing strategy was considered, the model assumed the independence of the

  19. Development of JFH1-based cell culture systems for hepatitis C virus genotype 4a and evidence for cross-genotype neutralization

    DEFF Research Database (Denmark)

    Scheel, Troels Kasper Høyer; Gottwein, Judith Margarete; Jensen, Tina Birk

    2008-01-01

    in serial passages. Sequence analysis of recovered viruses and subsequent reverse genetic studies revealed a vital dependence on one or two NS2 mutations, depending on the 4a/2a junction. Infectivity of ED43/JFH1 viruses was CD81 dependent. The genotype 4 cell culture systems permit functional analyses...... as well as drug and vaccine research on an increasingly important genotype in the Middle East, Africa, and Europe. We also developed genotype 1a intergenotypic recombinants from H77C with vital mutations in NS3. Using H77C/JFH1 and ED43/JFH1 viruses, we demonstrated high homologous neutralizing antibody...... titers in 1a and 4a patient sera, respectively. Furthermore, availability of JFH1 viruses with envelope proteins of the six major HCV genotypes permitted cross-neutralization studies; 1a and 4a serum cross-neutralized 1a, 4a, 5a, and 6a but not 2a and 3a viruses. Thus, the JFH1 intergenotypic...

  20. HCV-Induced Oxidative Stress: Battlefield-Winning Strategy

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    Khadija Rebbani

    2016-01-01

    Full Text Available About 150 million people worldwide are chronically infected with hepatitis C virus (HCV. The persistence of the infection is controlled by several mechanisms including the induction of oxidative stress. HCV relies on this strategy to redirect lipid metabolism machinery and escape immune response. The 3β-hydroxysterol Δ24-reductase (DHCR24 is one of the newly discovered host markers of oxidative stress. This protein, as HCV-induced oxidative stress responsive protein, may play a critical role in the pathogenesis of HCV chronic infection and associated liver diseases, when aberrantly expressed. The sustained expression of DHCR24 in response to HCV-induced oxidative stress results in suppression of nuclear p53 activity by blocking its acetylation and increasing its interaction with MDM2 in the cytoplasm leading to its degradation, which may induce hepatocarcinogenesis.

  1. Development and characterization of hepatitis C virus genotype 1-7 cell culture systems: role of CD81 and scavenger receptor class B type I and effect of antiviral drugs

    DEFF Research Database (Denmark)

    Gottwein, Judith M; Scheel, Troels K H; Jensen, Tanja B

    2009-01-01

    strains, as well as subtype 1b and 2b strains, we have completed a panel of culture systems for all major HCV genotypes. Efficient growth in Huh7.5 cells depended on adaptive mutations for HK6a/JFH1 (6a/2a, in E1 and E2) and J4/JFH1 (1b/2a, in NS2 and NS3); viability of J8/JFH1 (2b/2a) and QC69/JFH1 (7a/2......a) did not require adaptation. To facilitate comparative studies, we generated virus stocks of genotype 1-7 recombinants with infectivity titers of 10(3.7) to 10(5.2) 50% tissue culture infectious dose/mL and HCV RNA titers of 10(7.0) to 10(7.9) IU/mL. Huh7.5 cultures infected with genotype 1....... Recently, HCV research has been accelerated by cell culture systems based on the unique growth capacity of strain JFH1 (genotype 2a). By development of JFH1-based intergenotypic recombinants containing Core, envelope protein 1 and 2 (E1, E2), p7, and nonstructural protein 2 (NS2) of genotype 6a and 7a...

  2. Increased CD56(bright) NK cells in HIV-HCV co-infection and HCV mono-infection are associated with distinctive alterations of their phenotype.

    Science.gov (United States)

    Bhardwaj, Suvercha; Ahmad, Fareed; Wedemeyer, Heiner; Cornberg, Marcus; Schulze Zur Wiesch, Julian; van Lunzen, Jan; Sarin, Shiv K; Schmidt, Reinhold E; Meyer-Olson, Dirk

    2016-04-18

    HIV-HCV co-infection is associated with accelerated progression to hepatic fibrosis, cirrhosis and hepatocellular carcinoma than HCV mono-infection. The contribution of innate immunity during HIV-HCV co-infection has been a relatively under-investigated area. Natural killer (NK) cells are pivotal sentinels of innate immunity against viruses and tumour cells. In this study we evaluated the effect of HIV-HCV co-infection on peripheral blood NK cell subsets with emphasis on the phenotype of CD56(bright) NK cells. Sixty patients were included in the study; HIV mono-infected (n = 12), HCV mono-infected (n = 15), HCV-HIV co-infected (n = 21) and healthy controls (n = 16). PBMCs were isolated and immunophenotyping of NK cells was performed by flowcytometry. We observed an expansion of CD56(bright) NK cell subset in HIV-HCV co-infection as compared to healthy controls and HIV mono-infected group. All the infected groups had an upregulated expression of the activating receptor NKG2D on CD56(bright) NK cells in comparison to healthy controls while not differing amongst themselves. The expression of NKp46 in HIV-HCV co-infected group was significantly upregulated as compared to both HIV as well as HCV mono-infections while NKp30 expression in the HIV-HCV co-infected group significantly differed as compared to HIV mono-infection. The CD56(bright) NK cell subset was activated in HIV-HCV co-infection as assessed by the expression of CD69 as compared to healthy controls but was significantly downregulated in comparison to HIV mono-infection. CD95 expression on CD56(bright) NK cells followed the same pattern where there was an increased expression of CD95 in HIV mono-infection and HIV-HCV co-infection as compared to healthy controls. In contrast to CD69 expression, CD95 expression in HCV mono-infection was decreased when compared to HIV mono-infection and HIV-HCV co-infection. Finally, expression of CXCR3 on CD56(bright) NK cells was increased in HIV-HCV co-infection in comparison

  3. Burden of pediatric hepatitis C

    OpenAIRE

    El-Shabrawi, Mortada Hassan; Kamal, Naglaa Mohamed

    2013-01-01

    Hepatitis C virus (HCV) is a major health burden infecting 170-210 million people worldwide. Additional 3-4 millions are newly-infected annually. Prevalence of pediatric infection varies from 0.05%-0.36% in the United States and Europe; up to 1.8%-5.8% in some developing countries. The highest prevalence occurs in Egypt, sub-Saharan Africa, Amazon basin and Mongolia. HCV has been present in some populations for several centuries, notably genotypes 1 and 2 in West Africa. Parenteral anti-schis...

  4. Prevalence and Genotyping of Cryptosporidium Infection in Pet Parrots in North China

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    Xiao-Xuan Zhang

    2015-01-01

    Full Text Available Cryptosporidiosis is a worldwide zoonosis caused by Cryptosporidium spp., sometimes leading to severe diarrhea in humans and animals. In the present study, 311 parrots, belonging to four species, namely, Budgerigars (Melopsittacus undulatus, Lovebirds (Agapornis sp., Alexandrine parakeets (Psittacula eupatria, and Cockatiel (Nymphicus hollandicus, from Beijing and Weifang cities, were examined for Cryptosporidium spp. infection. Blood samples of each bird were examined using enzyme linked immunosorbent assay (ELISA and fecal samples were examined by Sheather’s sugar flotation technique. Prevalence of Cryptosporidium infection were 3.22% (10/311 and 0.64% (2/311 by ELISA and Sheather’s sugar flotation technique, respectively. Seroprevalence of Cryptosporidium infection in different breeds varied from 0 to 15.39%. Sequencing analysis showed that both positive samples from fecal samples belonged to Cryptosporidium avian genotype V. This is the first report of Cryptosporidium avian genotype V in Budgerigars. The results of the present study provided foundation-data for prevention and control of cryptosporidiosis in pet birds in China.

  5. Prevalence and Genotyping of Cryptosporidium Infection in Pet Parrots in North China.

    Science.gov (United States)

    Zhang, Xiao-Xuan; Zhang, Nian-Zhang; Zhao, Guang-Hui; Zhao, Quan; Zhu, Xing-Quan

    2015-01-01

    Cryptosporidiosis is a worldwide zoonosis caused by Cryptosporidium spp., sometimes leading to severe diarrhea in humans and animals. In the present study, 311 parrots, belonging to four species, namely, Budgerigars (Melopsittacus undulatus), Lovebirds (Agapornis sp.), Alexandrine parakeets (Psittacula eupatria), and Cockatiel (Nymphicus hollandicus), from Beijing and Weifang cities, were examined for Cryptosporidium spp. infection. Blood samples of each bird were examined using enzyme linked immunosorbent assay (ELISA) and fecal samples were examined by Sheather's sugar flotation technique. Prevalence of Cryptosporidium infection were 3.22% (10/311) and 0.64% (2/311) by ELISA and Sheather's sugar flotation technique, respectively. Seroprevalence of Cryptosporidium infection in different breeds varied from 0 to 15.39%. Sequencing analysis showed that both positive samples from fecal samples belonged to Cryptosporidium avian genotype V. This is the first report of Cryptosporidium avian genotype V in Budgerigars. The results of the present study provided foundation-data for prevention and control of cryptosporidiosis in pet birds in China.

  6. Challenges in Providing Treatment and Care for Viral Hepatitis among Individuals Co-Infected with HIV in Resource-Limited Settings

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    Wirach Maek-a-Nantawat

    2012-01-01

    Full Text Available Hepatitis B and C infections are prevalent among HIV-infected individuals with different epidemiologic profiles, modes of transmission, natural histories, and treatments. Southeast Asian countries are classified as “highly prevalent zones,” with a rate of hepatitis B and C coinfection in people living with HIV/AIDS of approximately 3.2–11%. Majority of hepatitis B coinfection is of genotype C. Most of the patients infected with hepatitis C in Thailand have genotype 3 which is significantly related to intravenous drug use whereas, in Vietnam, it is genotype 6. The options for antiretroviral drugs are limited and rely on global funds and research facilities. Only HBV treatment is available for free through the national health scheme. Screening tests for HBV and HCV prior to commencing antiretroviral treatment are low. Insufficient concern on hepatitis-virus-related liver malignancy and long-term hepatic morbidities is noted. Cost-effective HCV treatment can be incorporated into the national health program for those who need it by utilizing data obtained from clinical research studies. For example, patients infected with HCV genotype 2/3 with a certain IL-28B polymorphism can be treated with a shorter course of interferon and ribavirin which can also help reduce costs.

  7. Hepatitis C prevalence and risk factors in hemodialysis patients in Central Brazil: a survey by polymerase chain reaction and serological methods

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    Carneiro Megmar AS

    2001-01-01

    Full Text Available An hemodialysis population in Central Brazil was screened by polymerase chain reaction (PCR and serological methods to assess the prevalence of hepatitis C virus (HCV infection and to investigate associated risk factors. All hemodialysis patients (n=428 were interviewed in eight dialysis units in Goiânia city. Blood samples were collected and serum samples screened for anti-HCV antibodies by an enzyme-linked immunosorbent assay (ELISA. Positive samples were retested for confirmation with a line immunoassay (LIA. All samples were also tested for HCV RNA by the PCR. An overall prevalence of 46.7% (CI 95%: 42-51.5 was found, ranging from 20.7% (CI 95%: 8.8-38.1 to 90.4% (CI 95%: 79.9-96.4 depending on the dialysis unit. Of the 428 patients, 185 were found to be seropositive by ELISA, and 167 were confirmed positive by LIA, resulting in an anti-HCV prevalence of 39%. A total of 131 patients were HCV RNA-positive. HCV viremia was present in 63.5% of the anti-HCV-positive patients and in 10.3% of the anti-HCV-negative patients. Univariate analysis of risk factors showed that the number of previous blood transfusions, transfusion of blood before mandatory screening for anti-HCV, length of time on hemodialysis, and treatment in multiple units were associated with HCV positivity. However, multivariate analysis revealed that blood transfusion before screening for anti-HCV and length of time on hemodialysis were significantly associated with HCV infection in this population. These data suggest that nosocomial transmission may play a role in the spread of HCV in the dialysis units studied. In addition to anti-HCV screening, HCV RNA detection is necessary for the diagnosis of HCV infection in hemodialysis patients.

  8. Cost-utility analysis of ledipasvir/sofosbuvir for the treatment of genotype 1 chronic hepatitis C in Japan.

    Science.gov (United States)

    Igarashi, Ataru; Tang, Wentao; Guerra, Ines; Marié, Lucile; Cure, Sandrine; Lopresti, Michael

    2017-01-01

    Hepatitis C is the result of a ribonucleic acid (RNA) virus (hepatitis C virus; HCV). The Japan Society of Hepatology (JSH) estimated that 1.5-2 million people in Japan carry HCV. Six major HCV genotypes (GT) and a large number of subtypes have been described in the literature. In Japan, around 70% to 80% of people are infected with HCV genotype 1b. The progress of the disease primarily affects the liver and may lead to liver cirrhosis, hepatocellular carcinoma (HCC) and death. Sofosbuvir (SOF) is a nucleotide analogue NS5B inhibitor and ledipasvir (LDV) is an inhibitor of the HCV NS5A protein. They are combined in a single tablet regimen for the treatment of GT1 patients and resulted in sustained virological response (SVR) above 94% in large phase III trials. This analysis assesses the cost-utility of LDV/SOF in GT1 patients in Japan. A cohort of 10,000 patients was followed through a Markov model until they reached 100 years of age. GT1 treatment-naïve and experienced, non-cirrhotic and cirrhotic patients were studied separately. LDV/SOF was compared to several treatment regimens containing pegylated interferon (PEGIFN), telaprevir (TVR), simeprevir (SMV), daclatasvir (DCV), asunaprevir (ASV) and ribavirin (RBV). Discount rates of 2% were applied to costs and outcomes according to the Japanese guidelines. LDV/SOF was cost-effective against most comparators with incremental cost-effectiveness ratios (ICERs) below JPY 5,000,000. By applying a societal perspective, LDV/SOF was the dominant treatment strategy in all cases. Moreover, LDV/SOF reduced the number of cases of advanced liver disease. These results were robust to sensitivity analyses. LDV/SOF was cost-effective compared to most of the currently recommended treatments. Furthermore, LDV/SOF extends treatments to HCV-infected patients who are ineligible for interferon and RBV-based regimens. LDV/SOF thus has the potential to help reduce the burden of HCV in Japan.

  9. Prevalence of Porphyromonas gingivalis Four rag Locus Genotypes in Patients of Orthodontic Gingivitis and Periodontitis

    Science.gov (United States)

    Liu, Yi; Zhang, Yujie; Wang, Lili; Guo, Yang; Xiao, Shuiqing

    2013-01-01

    Porphyromonas gingivalis is considered as a major etiological agent in periodontal diseases and implied to result in gingival inflammation under orthodontic appliance. rag locus is a pathogenicity island found in Porphyromonas gingivalis. Four rag locus variants are different in pathogenicity of Porphyromonas gingivalis. Moreover, there are different racial and geographic differences in distribution of rag locus genotypes. In this study, we assessed the prevalence of Porphyromonas gingivalis and rag locus genotypes in 102 gingival crevicular fluid samples from 57 cases of gingivitis patients with orthodontic appliances, 25 cases of periodontitis patients and 20 cases of periodontally healthy people through a 16S rRNA-based PCR and a multiplex PCR. The correlations between Porphyromona.gingivalis/rag locus and clinical indices were analyzed. The prevalence of Porphyromonas gingivalis and rag locus genes in periodontitis group was the highest among three groups and higher in orthodontic gingivitis than healthy people (porthodontic gingivitis and mild-to-moderate periodontitis in Shandong. Porphyromonas.gingivalis carrying rag-1 has the strong virulence and could be associated with severe periodontitis. PMID:23593379

  10. Prevalence of HCV, HBV, and HIV Seropositivity among Cadavers Referred to Autopsy Hall of Legal Medicine Bureau of Tehran, Iran

    Directory of Open Access Journals (Sweden)

    Jaber Gharehdaghi

    2017-01-01

    Full Text Available A large number of dead bodies are referred to forensic autopsy halls for medicolegal examination. They can be a source of transmission of infectious diseases through direct contact or autopsy tools. The main aim of this study was to estimate the virus infection rates in the dead bodies. One thousand consecutive dead bodies that had been referred to autopsy hall of Legal Medicine Bureau of Tehran, Iran, during 2016, were included. The blood samples were analyzed in the laboratory for detection of HBs Ag, HBs Ab, HIV Ab, and HCV Ab, after providing informed consent from legal next of kin of the dead bodies. The general characteristics of the dead bodies were also collected by a checklist. Forty-seven cases of HIV seropositivity, 80 cases of HBs Ag seropositivity, and 97 cases for HCV Ab seropositivity were found. Among them, 27 cases of HIV, 40 cases of anti-HBC positive, and 94 cases of RIBA testing positive for HCV were proved through confirmatory tests. In other words, 2.6% of the dead bodies were infected with HIV, 3.8% with HBV, and 9% with HCV. The total infection rate was 15.5%. This is a worrying risk for pathologist and autopsy technicians.

  11. Prevalence of HCV, HBV, and HIV Seropositivity among Cadavers Referred to Autopsy Hall of Legal Medicine Bureau of Tehran, Iran.

    Science.gov (United States)

    Gharehdaghi, Jaber; Abedi Khorasgani, Mohammad Hassan; Ghadiani, Mohammad Hassan; Kazemifar, Amir Mohammad; Solhi, Hassan; Solhi, Sadra

    2017-01-01

    A large number of dead bodies are referred to forensic autopsy halls for medicolegal examination. They can be a source of transmission of infectious diseases through direct contact or autopsy tools. The main aim of this study was to estimate the virus infection rates in the dead bodies. One thousand consecutive dead bodies that had been referred to autopsy hall of Legal Medicine Bureau of Tehran, Iran, during 2016, were included. The blood samples were analyzed in the laboratory for detection of HBs Ag, HBs Ab, HIV Ab, and HCV Ab, after providing informed consent from legal next of kin of the dead bodies. The general characteristics of the dead bodies were also collected by a checklist. Forty-seven cases of HIV seropositivity, 80 cases of HBs Ag seropositivity, and 97 cases for HCV Ab seropositivity were found. Among them, 27 cases of HIV, 40 cases of anti-HBC positive, and 94 cases of RIBA testing positive for HCV were proved through confirmatory tests. In other words, 2.6% of the dead bodies were infected with HIV, 3.8% with HBV, and 9% with HCV. The total infection rate was 15.5%. This is a worrying risk for pathologist and autopsy technicians.

  12. Correlation between HIV and HCV in Brazilian prisoners: evidence for parenteral transmission inside prison Correlação entre HIV e HCV em prisioneiros brasileiros: evidência de transmissão parenteral no encarceramento

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    MN Burattini

    2000-10-01

    Full Text Available OBJECTIVE: It is an accepted fact that confinement conditions increase the risk of some infections related to sexual and/or injecting drugs practices. Mathematical techniques were applied to estimate time-dependent incidence densities of HIV infection among inmates. METHODS: A total of 631 prisoners from a Brazilian prison with 4,900 inmates at that time were interviewed and their blood drawn. Risky behavior for HIV infection was analyzed, and serological tests for HIV, hepatitis C and syphilis were performed, intended as surrogates for parenteral and sexual HIV transmission, respectively. Mathematical techniques were used to estimate the incidence density ratio, as related to the time of imprisonment. RESULTS: Prevalence were: HIV -- 16%; HCV -- 34%; and syphilis -- 18%. The main risk behaviors related to HIV infection were HCV prevalence (OR=10.49 and the acknowledged use of injecting drugs (OR=3.36. Incidence density ratio derivation showed that the risk of acquiring HIV infection increases with the time of imprisonment, peaking around three years after incarceration. CONCLUSIONS: The correlation between HIV and HCV seroprevalence and the results of the mathematical analysis suggest that HIV transmission in this population is predominantly due to parenteral exposure by injecting drug, and that it increases with time of imprisonment.OBJETIVO: É um fato correntemente aceito que as condições de confinamento aumentam o risco de algumas infecções relacionadas às práticas sexuais e/ou ao uso de drogas injetáveis. Realizou-se estudo para estimar a densidade de incidência da infecção pelo HIV na população prisional com aplicação de técnicas matemáticas. MÉTODOS: Foram entrevistados em São Paulo, SP, 631 prisioneiros da maior prisão da América do Sul, que abrigava aproximadamente 4.900 presos na ocasião do estudo. Foi colhido sangue da população entrevistada, analisado o risco para a infecção pelo HIV e realizados testes

  13. Prevalence of NS5B resistance-associated variants in treatment-naïve Asian patients with chronic hepatitis C.

    Science.gov (United States)

    Yang, Song; Xing, Huichun; Feng, Shenghu; Ju, Wei; Liu, Shunai; Wang, Xiaomei; Ou, Weini; Cheng, Jun; Pan, Calvin Q

    2018-02-01

    There is little information on the association between baseline non-structural protein (NS) 5b resistance-associated variants (RAVs) and treatment failure in hepatitis C patients. This study examined the frequencies of natural hepatitis C virus (HCV) NS5B resistance-associated variants (RAVs) in an Asian cohort. Samples from Asian HCV patients enrolled between October 2009 and September 2014 were analyzed for NS5B RAVs within the region from amino acid 230 to 371. Serum samples were tested by PCR genotyping, with sequence alignment performed using the neighbor-joining method. NS5B was detected by Sanger sequencing followed by Geno2pheno analysis. NS5B RAVs were detected in 80.52% (1199/1489) of patients; 68.4% (1019/1489) and 79.7% (1186/1489) were associated with resistance to sofosbuvir (SOF) and dasabuvir (DSV), respectively. These RAVs were present in 95% (1004/1058) of genotype 1b patients. When genotypes 1b and 2a were compared, SOF-associated RAVs were detected at a higher frequency in genotype 1b (94.8% [1004/1058] vs. 2.9% [9/309]; χ 2 = 1054.433, P C316H/N was more common in genotype 1b (94.7% [1002/1058] vs. 0% [0/309]; χ 2 = 1096.014, P C316Y/H/N/W was higher in genotype 1b (94.7% [1002/1058] vs. 0% [0/309]; χ 2 = 1096.014, P < 0.001). In conclusion, baseline SOF and DSV RAVs are common in Asian HCV patients and predominantly occur in genotype 1b.

  14. The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis.

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    Hans Dieter Nischalke

    Full Text Available BACKGROUND: An isoleucine>methionine mutation at position 148 in the PNPLA3 gene (p.I148M, rs738409 has recently been identified as a susceptibility factor for liver damage in steatohepatitis. Here, we studied whether the PNPLA3 rs738409 polymorphism also affects predisposition to hepatocellular carcinoma (HCC. METHODS: We compared distributions of PNPLA3 genotypes in 80 and 81 Caucasian patients with alcoholic and hepatitis C virus (HCV-associated HCC to 80 and 81 age- and sex-matched patients with alcohol-related and HCV-related cirrhosis without HCC, respectively. PNPLA3 genotypes in 190 healthy individuals from the same population served as reference. Potential confounders obesity, diabetes, HCV genotype and HBV co-infection were controlled by univariate and multivariate logistic regression with forward variable selection. RESULTS: PNPLA3 genotypes were in Hardy-Weinberg equilibrium for all study groups. The frequency of the 148M allele was significantly (p<0.001 increased in alcoholic cirrhosis with (53.7% and without HCC (36.2% but was not different between healthy controls (22.9% and patients with cirrhosis (25.3%; p = 0.545 and HCC (30.2%; p = 0.071 due to hepatitis C. HCC risk was highest in 148M/M homozygous patients with alcoholic liver disease (odds ratio (OR 16.8 versus healthy controls; 95% confidence interval (CI 6.68-42.43, p<0.001. Finally, multivariate regression confirmed 148M/M homozygosity (OR 2.8; 95%-CI: 1.24-6.42; p = 0.013 as HCC risk factor in alcoholic cirrhosis. In HCV-related cirrhosis only HCV genotype 1 was confirmed as a HCC risk factor (OR 4.2; 95%-CI: 1.50-11.52; p = 0.006. CONCLUSION: The PNPLA3 148M variant is a prominent risk factor for HCC in patients with alcoholic cirrhosis, while its effects are negligible in patients with cirrhosis due to HCV. This polymorphism provides an useful tool to identify individuals with particularly high HCC risk in patients with alcoholic liver disease that

  15. [Contribution of HCV core antigen testing in HCV diagnosis by test from the company Abbott Laboratories].

    Science.gov (United States)

    Trbusek, J

    2009-11-01

    Detection of HCV core antigen as direct marker of hepatitis C infection clearly improves diagnosis of this disease (especially reduction of window period) and brings broad clinical utilization. The company Abbott Laboratories offers fully automated laboratory test for measurement of HCV core antigen on ARCHITECT analyzers.

  16. The prevalence of the pre-existing hepatitis C viral variants and the evolution of drug resistance in patients treated with the NS3-4a serine protease inhibitor telaprevir

    Energy Technology Data Exchange (ETDEWEB)

    Rong, Libin [Los Alamos National Laboratory; Ribeiro, Ruy M [Los Alamos National Laboratory; Perelson, Alan S [Los Alamos National Laboratory

    2008-01-01

    Telaprevir (VX-950), a novel hepatitis C virus (HCV) NS3-4A serine protease inhibitor, has demonstrated substantial antiviral activity in patients infected with HCV genotype 1. Some patients experience viral breakthrough, which has been shown to be associated with emergence of telaprevir-resistant HCV variants during treatment. The exact mechanisms underlying the rapid selection of drug resistant viral variants during dosing are not fully understood. In this paper, we develop a two-strain model to study the pre-treatment prevalence of the mutant virus and derive an analytical solution of the mutant frequency after administration of the protease inhibitor. Our analysis suggests that the rapid increase of the mutant frequency during therapy is not due to mutant growth but rather due to the rapid and profound loss of wild-type virus, which uncovers the pre-existing mutant variants. We examine the effects of backward mutation and hepatocyte proliferation on the pre-existence of the mutant virus and the competition between wild-type and drug resistant virus during therapy. We then extend the simple model to a general model with multiple viral strains. Mutations during therapy do not play a significant role in the dynamics of various viral strains, although they are capable of generating low levels of HCV variants that would otherwise be completely suppressed because of fitness disadvantages. Hepatocyte proliferation may not affect the pretreatment frequency of mutant variants, but is able to influence the quasispecies dynamics during therapy. It is the relative fitness of each mutant strain compared with wild-type that determines which strain(s) will dominate the virus population. The study provides a theoretical framework for exploring the prevalence of pre-existing mutant variants and the evolution of drug resistance during treatment with other protease inhibitors or HCV polymerase inhibitors.

  17. Phylogeography, risk factors and genetic history of hepatitis C virus in Gabon, central Africa.

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    Richard Njouom

    Full Text Available BACKGROUND: The epidemiological and molecular characteristics of hepatitis C virus (HCV infection in the general population have been poorly investigated in Africa. The aim of this study was to determine the prevalence, genotype distribution and epidemic history of HCV in the Gabonese general population. METHODS/PRINCIPAL FINDINGS: A total of 4042 sera collected from adults in 220 villages in all nine administrative areas of the country were screened for antibodies to HCV. HCV NS5B region sequencing was performed for molecular characterization and population genetic analyses. Of 4042 tested sera, 455 (11.2% were positive. The seroprevalence of HCV varied significantly by administrative area, with the highest rate in Ogooué-Lolo province (20.4% and the lowest in Ogooué-Maritine province (3.7%. History of parenteral injections, past hospital admission and age over 55 years were independent risk factors for HCV infection (p<0.0001. Phylogenetic analyses showed that 91.9% of the strains were genotype 4 (HCV-4, 5.7% genotype 1 and 2.2% genotype 2. HCV-4 strains were highly heterogeneous, with more than eight subtypes; subtype 4e predominated (57.3%. Coalescence analyses indicated that subtype 4e was the oldest, with an estimated most recent common ancestor of 1702 [95% CI, 1418-1884]. The epidemic profile indicated that it spread exponentially during the first part of the 20th century, probably by iatrogenic transmission. CONCLUSIONS/SIGNIFICANCE: These results confirm the endemicity of HCV subtype 4e in Gabon and show that its spread is due to a cohort effect, with previous, possibly iatrogenic events. More extensive epidemiological studies are needed to better characterize the route of transmission and the dissemination of HCV in Gabon.

  18. Evolution of HVR-1 quasispecies after 1-year treatment in HIV/HCV-coinfected patients according to the pattern of response to highly active antiretroviral therapy.

    Science.gov (United States)

    Solmone, Mariacarmela; Girardi, Enrico; Lalle, Eleonora; Abbate, Isabella; D'Arminio Monforte, Antonella; Cozzi-Lepri, Alessandro; Alessandrini, Anna; Piscopo, Rita; Ebo, Francesca; Cosco, Lucio; Antonucci, Giorgio; Ippolito, Giuseppe; Capobianchi, Maria R

    2006-01-01

    Hepatitis C virus (HCV) variability is mainly attributed to the ability of the virus to respond to host immune pressure, acting as a driving force for the evolution of quasispecies. This study was aimed at studying the changes in HVR-1 heterogeneity and the evolution of HCV quasispecies in HIV/HCV-coinfected patients according to the pattern of response to highly active antiretroviral therapy (HAART). Sixteen HIV/HCV-coinfected patients harbouring HCV genotype 1 and who had been on HAART for at least 1 year, 8 showing increasing CD4+ T-cell counts (immunological responders) and 8 showing a stable or decreasing CD4+ T-cell counts (immunological nonresponders), were selected from a prospective cohort study. After 1 year of HAART, 11 patients showed HIV viral load HVR-1 region of HCV. Nonsynonymous/synonymous substitutions ratio (Ka/Ks), aminoacidic complexity (normalized Shannon entropy) and diversity (p-distance), were considered as parameters of quasispecies heterogeneity. After 1 year of HAART, heterogeneity of HVR-1 quasispecies significantly decreased in virological non-responders, whereas the heterogeneity tended to increase in virological responders. The differences in the evolution were less stringent, when considering immunological response. On the other hand, profound qualitative modifications of HVR-1 quasispecies were observed only in patients with both immunological and virological HAART response. On the whole, these findings suggest that, in patients undergoing HAART, the extent of HCV variability and the evolution of HVR-1 quasispecies is influenced by the pattern of response to antiretroviral therapy.

  19. Impact of Chronic Hepatitis C Virus Genotype 1b Infection on Triglyceride Concentration in Serum Lipoprotein Fractions

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    Tomohisa Nagano

    2015-08-01

    Full Text Available Reduced low-density lipoprotein (LDL cholesterol level is a characteristic feature of dyslipidemia in chronic hepatitis C virus (HCV infection. However, abnormality in serum triglyceride (TG has not been fully investigated. To clarify the impact of HCV genotype 1b (G1b infection and advanced fibrosis on serum TG profiles, TG concentrations in lipoprotein fractions were examined in fasting sera from 185 subjects with active or cleared HCV infection by high-performance liquid chromatography. Serum lipoproteins were fractionated into four classes: chylomicron, very low-density lipoprotein (VLDL, LDL, and high-density lipoprotein (HDL. Then, the significance of HCV G1b infection on TG levels in each lipoprotein fraction was determined using multiple regression models. We found that active HCV G1b infection was positively associated with high HDL-TG levels and low VLDL-TG levels, independent of other factors included in the regression model. In VLDL sub-fractions, active HCV infection was only found to be associated with low levels of large VLDL-TG. Similarly, advanced liver fibrosis in chronic HCV G1b infection was associated with high levels of LDL-TG, HDL-TG, and small VLDL-TG, independent of other clinical factors. These findings indicate that active HCV G1b infection and advanced fibrosis are closely associated with abnormal serum TG profiles.

  20. Molecular characterization of HCV in a Swedish county over 8 years (2002–2009 reveals distinct transmission patterns

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    Josefine Ederth

    2016-02-01

    Full Text Available Background: Hepatitis C virus (HCV is a major public health concern and data on its molecular epidemiology in Sweden is scarce. We carried out an 8-year population-based study of newly diagnosed HCV cases in one of Sweden's centrally situated counties, Södermanland (D-county. The aim was to characterize the HCV strains circulating, analyze their genetic relatedness to detect networks, and in combination with demographic data learn more about transmission. Methods: Molecular analyses of serum samples from 91% (N=557 of all newly notified cases in D-county, 2002–2009, were performed. Phylogenetic analysis (NS5B gene, 300 bp was linked to demographic data from the national surveillance database, SmiNet, to characterize D-county transmission clusters. The linear-by-linear association test (LBL was used to analyze trends over time. Results: The most prevalent subtypes were 1a (38% and 3a (34%. Subtype 1a was most prevalent among cases transmitted via sexual contact, via contaminated blood, or blood products, while subtype 3a was most prevalent among people who inject drugs (PWIDs. Phylogenetic analysis revealed that the subtype 3a sequences formed more and larger transmission clusters (50% of the sequences clustered, while the 1a sequences formed smaller clusters (19% of the sequences clustered, possibly suggesting different epidemics. Conclusion: We found different transmission patterns in D-county which may, from a public health perspective, have implications for how to control virus infections by targeted interventions.

  1. Model projections on the impact of HCV treatment in the prevention of HCV transmission among people who inject drugs in Europe

    DEFF Research Database (Denmark)

    Fraser, Hannah; Martin, Natasha K; Brummer-Korvenkontio, Henrikki

    2018-01-01

    BACKGROUND: Prevention of hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is critical to eliminating HCV in Europe. We estimate impact of current and scaled-up HCV treatment with and without scaling-up opioid substitution therapy (OST) and needle and syringe programmes (...

  2. Hepatitis B and C virus prevalence in couples attending an in vitro fertilization clinic in a tertiary care hospital in Saudi Arabia: comparison with ten years earlier.

    Science.gov (United States)

    Albadran, Asma; Hibshi, Ali; Saeed, Bahjat; Coskun, Serdar; Awartani, Khalid Arab

    2017-01-01

    Viral hepatitis B (HBV) and C (HCV) are a major public health problem in Saudi Arabia. Recent data has indicated a major reduction in viral hepatitis prevalence in Saudi population. However, there is limited data for infertile Saudi couples. To determine the prevalence of HCV and HBV attending an in vitro fertilization (IVF) clinic in Saudi Arabia between 2012 and 2015 to compare with the prevalence 10 years earlier in the same center. Retrospective prevalence study. Tertiary care center in Riyadh. Data on the prevalence of HBV and HCV was collected on all couples seen at the IVF unit between 2002-2005 and 2012-2015. Prevalence of HBV and HCV. In 4442 patients during 2002-2005 and 5747 patients during 2012-2015, the prevalence of HBV was significantly less in 2012-2015 compared with 2002-2005 (1.67% [97 patients] vs 4.7% [210 patients], P < .0001), respectively, but HCV prevalence was similar for the two periods (0.7% for both periods) (P=.887). The hepatitis B seroprevalence rate was higher in males compared to females during 2002-2005 (6.3% vs 3.1%) (P < .0001) and 2012-2015 (2.4% vs 1.1% ) (P < .0001), respectively. The significant drop in HBV prevalence was most likely due to the introduction of the vaccination program in 1989, while reasons for HCV prevalence remaining unchanged are unclear. No data on confounding factors that may have affected the prevalence.

  3. Hepatitis B virus genotypes circulating in Brazil: molecular characterization of genotype F isolates

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    Virgolino Helaine A

    2007-11-01

    Full Text Available Abstract Background Hepatitis B virus (HBV isolates have been classified in eight genotypes, A to H, which exhibit distinct geographical distributions. Genotypes A, D and F are predominant in Brazil, a country formed by a miscegenated population, where the proportion of individuals from Caucasian, Amerindian and African origins varies by region. Genotype F, which is the most divergent, is considered indigenous to the Americas. A systematic molecular characterization of HBV isolates from different parts of the world would be invaluable in establishing HBV evolutionary origins and dispersion patterns. A large-scale study is needed to map the region-by-region distribution of the HBV genotypes in Brazil. Results Genotyping by PCR-RFLP of 303 HBV isolates from HBsAg-positive blood donors showed that at least two of the three genotypes, A, D, and F, co-circulate in each of the five geographic regions of Brazil. No other genotypes were identified. Overall, genotype A was most prevalent (48.5%, and most of these isolates were classified as subgenotype A1 (138/153; 90.2%. Genotype D was the most common genotype in the South (84.2% and Central (47.6% regions. The prevalence of genotype F was low (13% countrywide. Nucleotide sequencing of the S gene and a phylogenetic analysis of 32 HBV genotype F isolates showed that a great majority (28/32; 87.5% belonged to subgenotype F2, cluster II. The deduced serotype of 31 of 32 F isolates was adw4. The remaining isolate showed a leucine-to-isoleucine substitution at position 127. Conclusion The presence of genotypes A, D and F, and the absence of other genotypes in a large cohort of HBV infected individuals may reflect the ethnic origins of the Brazilian population. The high prevalence of isolates from subgenotype A1 (of African origin indicates that the African influx during the colonial slavery period had a major impact on the circulation of HBV genotype A currently found in Brazil. Although most genotype F

  4. Prevalence of hepatitis B virus and hepatitis C virus among blood donors at a tertiary care hospital in India: a five-year study.

    Science.gov (United States)

    Meena, Monika; Jindal, Tarun; Hazarika, Anjali

    2011-01-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) are important transfusion-transmissible infections. This study was performed to assess the prevalence of HBV and HCV seropositivity among blood donors at a tertiary care hospital-based blood bank in India. The blood donation records over 5 years (2005-2009) were reviewed, retrospectively, for the prevalence and yearly trends of HBV and HCV seropositivity. A total of 94,716 donations were received. The overall number of HBV-seropositive donations was 1353 and that for HCV was 537, with the prevalence rates of 1.43% for hepatitis B surface antigen (HBsAg) and 0.57% for HCV. The seropositivity rate was higher in the replacement donors compared to the voluntary donors. The annual rates showed decreasing trends in case of HBsAg, but in case of HCV, there was a linear increase. Our study raises serious concerns regarding the HBV and HCV prevalence in our country. Although HBV showed decreasing trends, it cannot be relied upon because the donors were screened only for HBsAg. HCV is clearly on the rise. Stringent measures need to be taken on urgent basis including dissemination of information, strict screening of blood, inclusion of antibody to hepatitis B core antigen and other sensitive markers to the screening protocol, and better donor recruitment. © 2010 American Association of Blood Banks.

  5. The HIV, syphilis, and HCV epidemics among female sex workers in china: results from a serial cross-sectional study between 2008 and 2012.

    Science.gov (United States)

    Wang, Lu; Tang, Weiming; Wang, Lan; Qian, Shasha; Li, Yin-Ge; Xing, Jiannan; Li, Dongmin; Ding, Zhengwei; Babu, Giridhara R; Wang, Ning

    2014-07-01

    Studies on the transmission of human immunodeficiency virus (HIV) and sexually transmitted diseases in female sex workers (FSWs) have been limited primarily to inferences drawn by focusing on defined geographical areas. This serial cross-sectional study was conducted in mainland China from 2008 through 2012. Data for 827 079 participants was analyzed. We classified venues such as karaoke bars and hotels as high tier and venues such as hair salons and barbershops, massage parlors, and other public outdoor venues as low tier based on the participants' socioeconomic status. FSWs who worked at the venues and those who were present on the days of the survey were recruited. The prevalence of HIV decreased from 0.6% in 2008 to 0.3% in 2012, the syphilis prevalence ranged from 2.4% to 3.2% between 2008 and 2012, and hepatitis C virus (HCV) prevalence decreased from 0.9% in 2008 to 0.8% in 2012. Further, we found that HIV, syphilis, and HCV prevalence proportions were high in FSWs from low tiers. HIV, syphilis, and HCV prevalence among FSWs in our study decreased during the study period. Comprehensive intervention strategies, particularly those that focus on low-tier and older FSWs, are needed in order to decrease the disease burden in this population. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Prevalence and trend of hepatitis C virus infection among blood donors in Chinese mainland: a systematic review and meta-analysis

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    Ding Keqin

    2011-04-01

    Full Text Available Abstract Background Blood transfusion is one of the most common transmission pathways of hepatitis C virus (HCV. This paper aims to provide a comprehensive and reliable tabulation of available data on the epidemiological characteristics and risk factors for HCV infection among blood donors in Chinese mainland, so as to help make prevention strategies and guide further research. Methods A systematic review was constructed based on the computerized literature database. Infection rates and 95% confidence intervals (95% CI were calculated using the approximate normal distribution model. Odds ratios and 95% CI were calculated by fixed or random effects models. Data manipulation and statistical analyses were performed using STATA 10.0 and ArcGIS 9.3 was used for map construction. Results Two hundred and sixty-five studies met our inclusion criteria. The pooled prevalence of HCV infection among blood donors in Chinese mainland was 8.68% (95% CI: 8.01%-9.39%, and the epidemic was severer in North and Central China, especially in Henan and Hebei. While a significant lower rate was found in Yunnan. Notably, before 1998 the pooled prevalence of HCV infection was 12.87% (95%CI: 11.25%-14.56% among blood donors, but decreased to 1.71% (95%CI: 1.43%-1.99% after 1998. No significant difference was found in HCV infection rates between male and female blood donors, or among different blood type donors. The prevalence of HCV infection was found to increase with age. During 1994-1995, the prevalence rate reached the highest with a percentage of 15.78% (95%CI: 12.21%-19.75%, and showed a decreasing trend in the following years. A significant difference was found among groups with different blood donation types, Plasma donors had a relatively higher prevalence than whole blood donors of HCV infection (33.95% vs 7.9%. Conclusions The prevalence of HCV infection has rapidly decreased since 1998 and kept a low level in recent years, but some provinces showed relatively

  7. HCV viremia in clinical and biomedical perspective

    International Nuclear Information System (INIS)

    Hussain, A.B.; Tariq, W.Z.; Karamat, K.A.; Ghani, E.; Mushtaq, S.

    2000-01-01

    Sera of 172 patients from military / civil hospitals and general practitioners of Rawalpindi/Islamabad region and vicinity areas of northern Pakistan with anti-HCV IgG positive aerostats were tested at Armed Forces Institute of Pathology (AFIP), Rawalpindi, between July and November, 1997 for detection of HCV viremia by reverse transcriptases polymerase chain reaction (RT-PCR). Randomly selected 100 samples (40 viremia positive and 60 negative after PCR) were tested for serum alanine aminotransferase (ALT) levels. For each patient, information based upon clinical and laboratory findings was recorded on a performa to correlate the clinical and biochemical findings with the results of qualitative reverse transcriptase polymerase Chain Reaction (RT PCR) for HCV in Hepatitis C virus (HCV) infected patients. Of the total 172 HCV infected (Anti HCV Positive), 61(35.61%) patients were found to be viremic. Active infection was more frequent in the age of 30 years onwards. The past history of jaundice, surgical operation and chronic renal failure was more frequent with the viremia positive cases. Although, statistically insignificant, there was evidence of some association of diabetes mellitus with viremia ALT levels and its mean were higher in viremics, 27(73%) of 37 cases with a minimum three months history of interferon treatment for hepatitis C were found negative for viremia. (author)

  8. Differential sensitivity of 5'UTR-NS5A recombinants of hepatitis C virus genotypes 1-6 to protease and NS5A inhibitors

    DEFF Research Database (Denmark)

    Li, Yi-Ping; Ramirez, Santseharay; Humes, Daryl

    2014-01-01

    BACKGROUND & AIMS: Hepatitis C virus (HCV) therapy will benefit from the preclinical evaluation of direct-acting antiviral (DAA) agents in infectious culture systems that test the effects on different virus genotypes. We developed HCV recombinants comprising the 5' untranslated region-NS5A (5-5A...... daclatasvir. The 1a(TN) 5-5A and JFH1-independent full-length viruses had similar levels of sensitivity to the DAA agents, validating the 5-5A recombinants as surrogates for full-length viruses in DAA testing. Compared with the 1a(TN) full-length virus, the 3a(S52) 5-5A recombinant was highly resistant to all...... protease inhibitors, and the 4a(ED43) recombinant was highly resistant to telaprevir and boceprevir, but most sensitive to other protease inhibitors. Compared with other protease inhibitors, MK-5172 had exceptional potency against all HCV genotypes. The NS5A inhibitor daclatasvir had the highest potency...

  9. High prevalence of hepatitis B virus genotype C/C1 in the Minangkabau ethnic group in Indonesia

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    Siburian Marlinang D

    2013-01-01

    Full Text Available Abstract Background The Minangkabau is one of the major ethnic groups in Indonesia. Previous studies with a limited number of samples have shown a different prevalence of HBV/C in the Minangkabau compared to the Indonesian population in general. The aim of this study was to assess the HBV genotype distribution pattern and the prevalence of pre-S, T1753V and A1762T/G1764A mutations among the Minangkabau HBV carriers. The samples were collected from Padang, West Sumatera and from western Java. Mixed primers for specific genotypes were used to determine the HBV genotype. Pre-S or S genes were amplified, sequenced and aligned with reference sequences from GenBank to derive a phylogenetic tree for subgenotyping. Pre-S genes were also analyzed for mutations. The basal core promoter (BCP region was amplified and directly sequenced to analyze T1753V and A1762T/G1764A mutations. Results The predominant HBV genotype among the Minangkabau HBV carriers (n=117 was C (72.6% followed by B (24.8% and co-infection with B and C (2.6%. The prevalence of pre-S mutations, including both the pre-S deletion and pre-S2 start codon mutation, was 41.0%, and the T1753V and A1762T/G1764A mutations were found in 51.9% and 71.2% respectively. HBV/C1 was the predominant HBV subgenotype in the Minangkabau HBV carriers, and was found in 66.2%, followed by B3, B7, C8, B2, B9, C2, and C10 (18.3%, 7.0%, 2.8%, 1.4%, 1.4%, 1.4%, and 1.4% respectively. From samples that were found to be co-infected with HBV B and C, two samples were successfully cloned and subgenotyped, including one with mixed subgenotypes of B3 and C1, and another one with mixed subgenotypes of B7, C1, putative intergenotypic of B/A, and C/A. Furthermore, three samples from donors of non-Minangkabau ethnicity from Padang were found to be infected with an intragenotypic recombination form, including a putative recombinant of B8/B3 and B9/B7. Conclusion HBV/C with subgenotype C1 was the predominant HBV genotype among

  10. High prevalence of HBV infection, detection of subgenotypes F1b, A2, and D4, and differential risk factors among Mexican risk populations with low socioeconomic status.

    Science.gov (United States)

    Jose-Abrego, Alexis; Panduro, Arturo; Fierro, Nora A; Roman, Sonia

    2017-12-01

    Hepatitis B virus (HBV) infection may be underestimated among high-risk individuals in regions of low HBs antigenemia. This study aimed to assess HBV serological markers, genotypes, and risk factors in Mexican patients with risk of HBV infection and low socioeconomic status. Demographics, clinical, and risk factor data were collected in patients with HIV (n = 289), HCV (n = 243), deferred blood donors (D-BD) (n = 83), and two native populations, Mixtecos (n = 57) and Purepechas (n = 44). HBV infection was assessed by HBsAg, anti-HBc, and HBV-DNA testing. Overall, patients had low education and very-low income. Totally, HBsAg prevalence was 16.5% (113/684) ranging from 0.7% (HCV) to 37.3% (D-BD), while anti-HBc was 30.2% (207/684). Among 52 sequences, genotypes H (n = 34, 65.4%), G (n = 4, 7.7%), subgenotypes F1b (n = 7, 13.5%), A2 (n = 6, 11.5%), and D4 (n = 1, 1.9%) were detected. Surgeries, sexual promiscuity, and blood transfusions had a differential pattern of distribution. In HCV patients, single (OR = 5.84, 95%Cl 1.91-17.80, P = 0.002), MSM (OR = 4.80, 95%Cl 0.75-30.56, P = 0.097), and IDU (OR = 2.93, 95%CI 1.058-8.09, P = 0.039) were predictors for HBV infection. While IDU (OR = 2.68, 95%CI 1.08-6.61, P = 0.033) and MSM (OR = 2.64, 95%CI 1.39-5.04, P = 0.003) were predictors in HIV patients. In this group, MSM was associated with HBsAg positivity (OR = 3.45, 95%CI 1.48-8.07, P = 0.004) and IDU with anti-HBc positivity (OR = 5.12, 95%CI 2.05-12.77, P HBV markers, a high prevalence of HBV infection, a differential distribution of HBV genotypes, including subgenotypes F1b, A2, and D4, as well as risk factors in low-income Mexican risk groups were detected. © 2017 Wiley Periodicals, Inc.

  11. Epidemic dynamics of two coexisting hepatitis C virus subtypes.

    Science.gov (United States)

    Jiménez-Hernández, Nuria; Torres-Puente, Manuela; Bracho, Maria Alma; García-Robles, Inmaculada; Ortega, Enrique; del Olmo, Juan; Carnicer, Fernando; González-Candelas, Fernando; Moya, Andrés

    2007-01-01

    Hepatitis C virus (HCV) infection affects about 3% of the human population. Phylogenetic analyses have grouped its variants into six major genotypes, which have a star-like distribution and several minor subtypes. The most abundant genotype in Europe is the so-called genotype 1, with two prevalent subtypes, 1a and 1b. In order to explain the higher prevalence of subtype 1b over 1a, a large-scale sequence analysis (100 virus clones) has been carried out over 25 patients of both subtypes in two regions of the HCV genome: one comprising hypervariable region 1 and another including the interferon sensitivity-determining region. Neither polymorphism analysis nor molecular variance analysis (attending to intra- and intersubtype differences, age, sex and previous history of antiviral treatment) was able to show any particular difference between subtypes that might account for their different prevalence. Only the demographic history of the populations carrying both subtypes and analysis of molecular variance (AMOVA) for risk practice suggested that the route of transmission may be the most important factor to explain the observed difference.

  12. Treatment response in HCV related chronic hepatitis

    International Nuclear Information System (INIS)

    Hussain, A.B.; Hussain, T.; Hussain, S.; Masood, A.; Kazmi, Y.; Tariq, W.Z.; Karamat, K.A.

    2004-01-01

    Objective: To evaluate the virological response to treatment with interferon and ribavirin in-patients with hepatitis C related liver disease. Material and Methods: Two hundred seventy-nine patients were included in the study. These patients had taken interferon and ribavirin treatment for HCV related chronic hepatitis, and were referred to AFIP for HCV RNA testing by polymerase chain reaction (PCR) between January 2002 and September 2002. Out of 279 cases, 229 had taken the treatment for 06 or 12 months and were tested for end-of-treatment response (ETR). Fifty patients had completed there treatment regimens of 6 or 12 months treatment, at least 24 weeks before their PCR test and were having follow-up testing for sustained viral response (SVR). The sera of these patients were tested for HCV RNA by PCR, using a commercial kit of Amplicor (Roche) for qualitative detection of HCV RNA. Results: Out of 229 cases tested for end-of-treatment response, 198 (86.5%) had no detectable HCV RNA (responders) and 31 (13.50%) were PCR positive (non-responders). Thirty-eight out of 50 cases, tested for a sustained viral response, had a negative result for HCV PCR thus showing sustained response rate of 76%. Conclusion: The viral remission/response to interferon and ribavirin combination therapy in our patients was better than that quoted in other regions. (author)

  13. Virological Mechanisms in the Coinfection between HIV and HCV

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    Maria Carla Liberto

    2015-01-01

    Full Text Available Due to shared transmission routes, coinfection with Hepatitis C Virus (HCV is common in patients infected by Human Immunodeficiency Virus (HIV. The immune-pathogenesis of liver disease in HIV/HCV coinfected patients is a multifactorial process. Several studies demonstrated that HIV worsens the course of HCV infection, increasing the risk of cirrhosis and hepatocellular carcinoma. Also, HCV might increase immunological defects due to HIV and risk of comorbidities. A specific cross-talk among HIV and HCV proteins in coinfected patients modulates the natural history, the immune responses, and the life cycle of both viruses. These effects are mediated by immune mechanisms and by a cross-talk between the two viruses which could interfere with host defense mechanisms. In this review, we focus on some virological/immunological mechanisms of the pathogenetic interactions between HIV and HCV in the human host.

  14. Genetic Barrier to Direct Acting Antivirals in HCV Sequences Deposited in the European Databank.

    Directory of Open Access Journals (Sweden)

    Dimas Alexandre Kliemann

    Full Text Available Development of resistance results from mutations in the viral genome, and the presence of selective drug pressure leads to the emergence of a resistant virus population. The aim of this study was to analyze the impact of genetic variability on the genetic barrier to drug resistance to DAAs.The genetic barrier was quantified based on the number and type of nucleotide mutations required to impart resistance, considering full-length HCV NS3, NS5A and NS5B regions segregated by genotype into subtypes 1a, 1b, 2a, 2b and 3a. This study analyzeds 789 NS3 sequences, 708 sequences and 536 NS5B sequences deposited in the European Hepatitis C Virus Database, in the following resistance-associated positions: NS3: F43/I/L/S/V, Q80K/R, R155K/G, A156G/S/T and D168A/C/E/G/H/N/T/V/Y; NS5A: L/M28A/T/V, Q30E/H/R, L31F/I/M/V, H58D or P58S and Y93C/F/H/N/S; NS5B: S282P/R/T, C316H/N/Y, S368T, Y448C/H, S556G/R, D559R.Variants that require only one transversion in NS3 were found in 4 positions and include F43S, R80K, R155K/G and A156T. The genetic barrier to resistance shows subtypic differences at position 155 of the NS3 gene where a single transition is necessary in subtype 1a. In the NS5A gene, 5 positions where only one nucleotide change can confer resistance were found, such as L31M which requires one transversion in all subtypes, except in 0.28% of 1b sequences; and R30H, generated by a single transition, which was found in 10.25% of the sequences of genotype 1b. Other subtypic differences were observed at position 58, where resistance is less likely in genotype 1a because a transversion is required to create the variant 58S. For the NS5B inhibitors, the genetic barrier at positions conferring resistance was nearly identical in subtypes 1a and 1b, and single transitions or transversions were necessary in 5 positions to generate a drug-resistant variant of HCV. The positions C316Y and S556D required only one transition in all genotypes, Y448H and S556 G

  15. Autophagy in HCV Infection: Keeping Fat and Inflammation at Bay

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    Tiziana Vescovo

    2014-01-01

    Full Text Available Hepatitis C virus (HCV infection is one of the main causes of chronic liver disease. Viral persistence and pathogenesis rely mainly on the ability of HCV to deregulate specific host processes, including lipid metabolism and innate immunity. Recently, autophagy has emerged as a cellular pathway, playing a role in several aspects of HCV infection. This review summarizes current knowledge on the molecular mechanisms that link the HCV life cycle with autophagy machinery. In particular, we discuss the role of HCV/autophagy interaction in dysregulating inflammation and lipid homeostasis and its potential for translational applications in the treatment of HCV-infected patients.

  16. Cost comparison of treating chronic hepatitis C genotype one with pegylated interferons in Ukraine

    NARCIS (Netherlands)

    E.A. Mandrik (Olena); S. Knies (Saskia); O. Golubovska (Olha); O. Duda (Oleksandr); L. Dudar (Larisa); S. Fedorchenko (Sergiy); O. Zaliska (Ožlha); J.L. Severens (Hans)

    2015-01-01

    textabstractBased on the pivotal trial showing no clinicallyrelevant differences between pegylated interferon α-2b (Peg-α-2b) and α-2a (Peg-α-2a) combined with ribavirin for treatment of chronic hepatitis C virus (HCV) genotype 1 infection in Ukraine, a cost-minimization analysis was performed using

  17. Hiv/hbv, hiv/hcv and hiv/htlv-1 co infection among injecting drug user patients hospitalized at the infectious disease ward of a training hospital in iran

    International Nuclear Information System (INIS)

    Alavi, S.M.; Etemadi, A.

    2007-01-01

    To assess the prevalence and risk factors for HBV, HCV and HTLV-I co-infection in the Iranian HIV positive Injecting Drug Users (IDU) patients admitted in hospital. Analyses were based on 154 male IDU patients admitted in Infectious disease ward of Razi Hospital, Ahwaz, Iran, from April 2001 to March 2003. All of them had been tested for HIV infection (Elisa-antibody and Western blot), HBV surface antigen, HCV antibody and HTLV-1 antibody. One hundred and four patients (67.53%) were identified as HIV infected. Among HIV infected, HB surface antigen, HCV antibody and HTLV-I antibody were positive in 44.23% and 74.04% and 16.33% patients respectively. HCV/HBV/HIV and HCV/HBV/HIV/HTLV-1 co-infection were 20.20% and 8.65% respectively. Co-infection with HBV or HCV or HTLV-1 is common among hospitalized HIV-infected IDU patients in the region of study. HIV disease outcomes appear to be adversely affected by HBV/HCV/HTLV-I co-infection, so identification of these viral infections is recommended as routine tests for this population. (author)

  18. Rise and fall of HCV-related hepatocellular carcinoma in Italy: a long-term survey from the ITA.LI.CA centres.

    Science.gov (United States)

    Cazzagon, Nora; Trevisani, Franco; Maddalo, Gemma; Giacomin, Anna; Vanin, Veronica; Pozzan, Caterina; Poggio, Paolo Del; Rapaccini, Gianludovico; Nolfo, Anna M Di; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Giannini, Edoardo G; Caturelli, Eugenio; Chiaramonte, Maria; Foschi, Francesco G; Cabibbo, Giuseppe; Felder, Martina; Ciccarese, Francesca; Missale, Gabriele; Baroni, Gianluca Svegliati; Morisco, Filomena; Pecorelli, Anna; Farinati, Fabio

    2013-10-01

    Hepatitis C virus (HCV) is the leading aetiological factor of HCC in the western world where, overall, its incidence is increasing, despite data suggesting an initial drop in some areas. The aim of this study was to evaluate epidemiology, clinical features and survival of HCV-related HCC (HCV-HCC) in a wide time range in Italy. Multicentre retrospective study including 3695 patients prospectively recruited by the ITA.LI.CA group. Patients were classified into three subgroups according to aetiology (Group A[GA], pure HCV; Group B[GB], HCV + cofactors; and Group C[GC], non-HCV) and in 5 time cohorts (5 years each), according to the year of diagnosis. Age, gender, Child-Pugh score, modality of diagnosis, stage, presence of thrombosis/metastases, type of treatment and survival were analysed. A total of 1801 GA patients, 445 GB and 1333 GC were recruited. The number of GA patients peaked in the 1996-2000, gradually dropping thereafter (P < 0.0001), as observed for GB (P < 0.0001). Age at diagnosis increased (P < 0.0001), while percentage of patients diagnosed during surveillance and stage improved only in GA (P = 0.02 and P = 0.003 respectively). The survival significantly increased over time particularly in GA (median 37 months) and was longer in GA than in GB and GC (P < 0.0001). The prevalence of HCC-HCV is decreasing in Italy since 2001. HCV-HCC patients are older, more frequently diagnosed under surveillance and in an earlier stage. HCC survival improved in the last 15 years and is significantly higher in patients with HCV-HCC. We therefore expect a further drop in both incidence and mortality for HCV-HCC in the years to come. © 2013 John Wiley & Sons A/S.

  19. HCV and HBV coexist in HBsAg-negative patients with HCV viremia; possibility of coinfection in these patients must be considered in HBV-high endemic area

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong Soon [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1998-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers and is highly associated with HBV infection in Korea. It has been suggested that HCV core protein may impair the polymerase activity of HBV in vitro, potentially lowering HBV titre in coinfected patients. The aim of this study was to confirm the coexistence of HBV viremia in HCV infected patients HCC who have apparent HBsAg seronegativity. The serological profiles of HBV and HCV in 616 patients with HCC were analysed and coinfection rate of HBV and HCV investigated. Sera were obtained from 16 patients who were both anti-HCV and HCV RNA positive but HbsAg negative, and tested for HBV BY PCR. As a control group, sera were obtained from 15 patients with HCC and 30 non-A abd non-B chronic hepatitis patients without HCC; both were anti-HCV, HCV-RNA, and HBsAg negative and tested for HBV PCR. Of 616 patients with HCC, 450 (73.1 %) had current HBV infection, 48 (7.8 %) had anti-HCV antibodies, and nine (1.5 %) had viral markers of both HCV abd HBV by serological profiles. Of 27 the patients with HCV viremia and HBsAg seronegativity, 14 (51.9 %) showed HBV viremia by PCR. In contrast, of the 75 patients in the control group who were both HCV PCR negative and HBsAg negative, five (11.1 %) showed HBV viremia by PCR. The PCR for HBV revealed coexistent HBV viremia in HCV viremia patients, despite HBsAg negativity by EIA. In HBV-endemic areas, the possibility of coinfection of HBV in HBsAg-negative patients with HCV viremia should be considered and molecular analysis for HBV-DNA performed. (author). 18 refs., 4 tabs.

  20. HCV and HBV coexist in HBsAg-negative patients with HCV viremia; possibility of coinfection in these patients must be considered in HBV-high endemic area

    International Nuclear Information System (INIS)

    Lee, Dong Soon

    1998-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers and is highly associated with HBV infection in Korea. It has been suggested that HCV core protein may impair the polymerase activity of HBV in vitro, potentially lowering HBV titre in coinfected patients. The aim of this study was to confirm the coexistence of HBV viremia in HCV infected patients HCC who have apparent HBsAg seronegativity. The serological profiles of HBV and HCV in 616 patients with HCC were analysed and coinfection rate of HBV and HCV investigated. Sera were obtained from 16 patients who were both anti-HCV and HCV RNA positive but HbsAg negative, and tested for HBV BY PCR. As a control group, sera were obtained from 15 patients with HCC and 30 non-A abd non-B chronic hepatitis patients without HCC; both were anti-HCV, HCV-RNA, and HBsAg negative and tested for HBV PCR. Of 616 patients with HCC, 450 (73.1 %) had current HBV infection, 48 (7.8 %) had anti-HCV antibodies, and nine (1.5 %) had viral markers of both HCV abd HBV by serological profiles. Of 27 the patients with HCV viremia and HBsAg seronegativity, 14 (51.9 %) showed HBV viremia by PCR. In contrast, of the 75 patients in the control group who were both HCV PCR negative and HBsAg negative, five (11.1 %) showed HBV viremia by PCR. The PCR for HBV revealed coexistent HBV viremia in HCV viremia patients, despite HBsAg negativity by EIA. In HBV-endemic areas, the possibility of coinfection of HBV in HBsAg-negative patients with HCV viremia should be considered and molecular analysis for HBV-DNA performed. (author). 18 refs., 4 tabs

  1. Knowledge of HBV and HCV and individuals' attitudes toward HBV- and HCV-infected colleagues: a national cross-sectional study among a working population in Japan.

    Directory of Open Access Journals (Sweden)

    Hisashi Eguchi

    Full Text Available Prejudice and discrimination in the workplace regarding the risk of transmission of Hepatitis B virus (HBV and Hepatitis C virus (HCV are increased by excess concerns due to a lack of relevant knowledge. Education to increase knowledge about HBV and HCV and their prevention could be the first step to reduce prejudice and discrimination. This study aimed to determine the association between the level of knowledge and negative attitudes toward HBV- and HCV-infected colleagues among the Japanese working population. An online anonymous nationwide survey involving about 3,000 individuals was conducted in Japan. The questionnaire consisted of knowledge of HBV and HCV, and attitudes toward HBV- and HCV-infected colleagues in the workplace. Knowledge was divided into three categories: "ensuring daily activities not to be infected"; "risk of infection"; and "characteristics of HBV/HCV hepatitis", based on the result of factor analysis. Multiple logistic regression analysis was applied. A total of 3,129 persons responded to the survey: 36.0% reported they worried about the possibility of transmission of HBV and HCV from infected colleagues; 32.1% avoided contact with infected colleagues; and 23.7% had prejudiced opinions about HBV and HCV infection. The participants were classified into tertiles. A higher level of knowledge of HBV and HCV was significantly associated with these three negative attitudes (P for trend < 0.005. This study suggests that increasing knowledge may decrease individuals' negative attitudes towards HBV- and HCV-infected colleagues. Thus, we should promote increased knowledge of HBV and HCV in stages to reduce negative attitudes toward HBV- and HCV-infected colleagues.

  2. Epidemiological profile and risk factors of HIV and HBV/HCV co-infection in Fujian Province, southeastern China.

    Science.gov (United States)

    Wu, Shouli; Yan, Pingping; Yang, Tianfei; Wang, Zhenghua; Yan, Yansheng

    2017-03-01

    This study aimed to investigate the epidemiological features of HIV-infected subjects co-infected with HBV/HCV in Fujian Province, southeastern China, and identify the risk factors. Blood samples were collected from 2,028 HIV antibody-positive subjects in Fujian Province. Serum HBsAg and anti-HCV antibody were detected, and CD4 + T cell count was measured. Of the 2,028 subjects, the prevalence of HIV-HBV, HIV-HCV, and HIV-HBV-HCV co-infections was 16.22%, 3.7%, and 0.79%, respectively. Man (OR = 1.912, 95% CI: 1.371-2.667), key population (OR = 0.756, 95% CI: 0.57-0.976) and detainee (OR = 0.486, 95% CI: 0.259-0.909) were risk factors of HIV-HBV co-infection, and man (OR = 2.227, 95% CI: 1.096-4.525), minority (OR = 5.04, 95% CI: 1.696-14.98), junior high school or lower education (OR = 2.32, 95% CI: 1.071-5.025), intravenous drug use (OR = 38.46, 95% CI: 11.46-129.11) and detainee (OR = 5.687, 95% CI: 2.44-13.25) were risk factors of HIV-HCV co-infection. In addition, a lower mean CD4 + T cell count was measured in HIV/HBV and HIV/HCV co-infected subjects than in HIV-infected subjects among the untreated individuals, while in the treated populations, a higher mean CD4 + T cell count was detected in HIV/HBV and HIV/HCV co-infected subjects than in HIV-infected subjects. HIV co-infection with HBV or HCV, notably HIV-HBV co-infection, is widespread in southeastern China. Hepatitis virus screening should be included in monitoring of HIV infection, and HIV and hepatitis virus co-infection should be considered during the development of HIV antiretroviral therapy scheme. J. Med. Virol. 89:443-449, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Influence of IL28B polymorphisms on response to a lower-than-standard dose peg-IFN-α 2a for genotype 3 chronic hepatitis C in HIV-coinfected patients.

    Directory of Open Access Journals (Sweden)

    Luis F López-Cortés

    Full Text Available Data on which to base definitive recommendations on the doses and duration of therapy for genotype 3 HCV/HIV-coinfected patients are scarce. We evaluated the efficacy of a lower peginterferon-α 2a dose and a shorter duration of therapy than the current standard of care in genotype 3 HCV/HIV-coinfected patients.Pilot, open-label, single arm clinical trial which involved 58 Caucasian HCV/HIV-coinfected patients who received weekly 135 µg peginterferon-α 2a plus ribavirin 400 mg twice daily during 20 weeks after attaining undetectable viremia. The relationships between baseline patient-related variables, including IL28B genotype, plasma HCV-RNA, ribavirin dose/kg, peginterferon-α 2a and ribavirin levels with virological responses were analyzed. Only 4 patients showed lack of response and 5 patients dropped out due to adverse events related to the study medication. Overall, sustained virologic response (SVR rates were 58.3% by intention-to-treat and 71.4% by per protocol analysis, respectively. Among patients with rapid virologic response (RVR, SVR and relapses rates were 92.6% and 7.4%, respectively. No relationships were observed between viral responses and ribavirin dose/kg, peginterferon-α 2a concentrations, ribavirin levels or rs129679860 genotype.Weekly 135 µg pegIFN-α 2a could be as effective as the standard 180 µg dose, with a very low incidence of severe adverse events. A 24-week treatment duration appears to be appropriate in patients achieving RVR, but extending treatment up to just 20 weeks beyond negativization of viremia is associated with a high relapse rate in those patients not achieving RVR. There was no influence of IL28B genotype on the virological responses.ClinicalTrials.gov NCT00553930.

  4. Prevalence of hepatitis B, hepatitis C and human immunodeficiency viruses, and evaluation of risk factors for transmission: Report of a population screening in Nigeria

    Directory of Open Access Journals (Sweden)

    U C Okonkwo

    2017-04-01

    Full Text Available Background. Hepatitis B virus (HBV, hepatitis C virus (HCV and HIV are common blood-borne infections unevenly distributed across regions in Nigeria. Few population-based prevalence studies have been done in Nigeria. Objective. To determine the prevalence of HBV, HCV and HIV and risk factors for infection with these viruses in a Nigerian population. Methods. Hepatitis B surface antigen, anti-HCV and HIV were assayed in 1 498 healthy adult participants. A structured questionnaire was used to assess risk factors for viral acquisition. Bivariate analysis was used to compare differences in sociodemographic characteristics. Significant risk factors were identified by stepwise logistic regression. A p-value <0.05 was considered significant. Results. The prevalences of HBV, HCV and HIV were 8.8%, 10.0% and 12.9%, respectively, with urban/rural disparity. HBV/HCV positivity was higher among males than females. The reverse was true for HIV. Age was significantly associated with being HBV-, HCV- or HIV-positive. Communal use of a toothbrush was significantly associated with HBV positivity in the final model (odds ratio 2.46, 95% confidence interval 1.45 - 4.18. Conclusions. The prevalence of HBV, HCV and HIV infection is high in Nigeria, with urban/rural disparity. HCV may be more of a public health concern than HBV in some communities. Population-based studies are required to provide vital data to inform optimal national control strategies.

  5. Boceprevir plus pegylated interferon/ribavirin to re-treat hepatitis C virus genotype 1 in HIV–HCV co-infected patients: final results of the Spanish BOC HIV–HCV Study

    Directory of Open Access Journals (Sweden)

    M. Laguno

    2016-12-01

    Conclusions: Response-guided therapy with BOC in combination with PEG-IFN/RBV led to an overall SVR rate of 67%, but an SVR rate of only 51% in patients with cirrhosis. The therapy was generally well tolerated. Although the current standards of care do not include BOC + PEG-IFN/RBV, the authors believe that this combination can be beneficial in situations where new HCV direct antiviral agent interferon-free therapies are not available yet.

  6. Prevalence and risk factors for Hepatitis C and HIV-1 infections among pregnant women in Central Brazil

    Directory of Open Access Journals (Sweden)

    Stefani Mariane MA

    2009-07-01

    Full Text Available Abstract Background Hepatitis C (HCV and human immunodeficiency virus (HIV infections are a major burden to public health worldwide. Routine antenatal HIV-1 screening to prevent maternal-infant transmission is universally recommended. Our objectives were to evaluate the prevalence of and potential risk factors for HCV and HIV infection among pregnant women who attended prenatal care under the coverage of public health in Central Brazil. Methods Screening and counselling for HIV and HCV infections was offered free of charge to all pregnant women attending antenatal clinic (ANC in the public health system, in Goiania city (~1.1 million inhabitants during 2004–2005. Initial screening was performed on a dried blood spot collected onto standard filter paper; positive or indeterminate results were confirmed by a second blood sample. HCV infection was defined as a positive or indeterminate sample (EIA test and confirmed HCV-RNA technique. HIV infection was defined according to standard criteria. Factors associated with HIV and HCV infections were identified with logistic regression. The number needed to screen (NNS to prevent one case of infant HIV infection was calculated using the Monte Carlo simulation method. Results A total of 28,561 pregnant women were screened for HCV and HIV-1 in ANC. Mean maternal age was 23.9 years (SD = 5.6, with 45% of the women experiencing their first pregnancy. Prevalence of HCV infection was 0.15% (95% CI 0.11%–0.20%, and the risk increased with age (p Conclusion The prevalence of HIV and HCV infections were low among pregnant women, with high acceptability rates in the opt-in strategy in primary care. Older maternal age was a risk factor for HCV and antenatal HCV testing does not fulfill the requirements for screening recommendation. The finding of higher risk of HIV-1 infection among black women despite being in consonance with the HIV-1 ethnic pattern in some American regions cannot be ruled out to be a surrogate

  7. Efficient Culture Adaptation of Hepatitis C Virus Recombinants with Genotype-Specific Core-NS2 by Using Previously Identified Mutations

    DEFF Research Database (Denmark)

    Scheel, Troels Kasper Høyer; Gottwein, Judith M; Carlsen, Thomas H R

    2011-01-01

    Hepatitis C virus (HCV) is an important cause of chronic liver disease, and interferon-based therapy cures only 40 to 80% of patients, depending on HCV genotype. Research was accelerated by genotype 2a (strain JFH1) infectious cell culture systems. We previously developed viable JFH1-based...... (HC-TN and DH6), 1b (DH1 and DH5), and 3a (DBN) isolates, using previously identified adaptive mutations. Introduction of mutations from isolates of the same subtype either led to immediate efficient virus production or accelerated culture adaptation. The DH6 and DH5 recombinants without introduced...... mutations did not adapt to culture. Universal adaptive effects of mutations in NS3 (Q1247L, I1312V, K1398Q, R1408W, and Q1496L) and NS5A (V2418L) were investigated for JFH1-based genotype 1 to 5 core-NS2 recombinants; several mutations conferred adaptation to H77C (1a), J4 (1b), S52 (3a), and SA13 (5a...

  8. Hepatic HMOX1 expression positively correlates with Bach-1 and miR-122 in patients with HCV mono and HIV/HCV coinfection.

    Science.gov (United States)

    Jabłonowska, Elżbieta; Wójcik, Kamila; Szymańska, Bożena; Omulecka, Aleksandra; Cwiklińska, Hanna; Piekarska, Anna

    2014-01-01

    To analyze the expression of HMOX1 and miR-122 in liver biopsy samples obtained from HCV mono-and HIV/HCV co-infected patients in relation to selected clinical parameters, histological examination and IL-28B polymorphism as well as to determine whether HMOX1 expression is dependent on Bach-1. The study group consisted of 90 patients with CHC: 69 with HCV mono and 21 with HIV/HCV co-infection. RT-PCR was used in the analysis of HMOX1, Bach-1 and miR-122 expression in liver biopsy samples and in the assessment of IL-28B single-nucleotide polymorphism C/T (rs12979860) in the blood. Moreover in liver biopsy samples an analysis of HO-1 and Bach-1 protein level by Western Blot was performed. HCV mono-infected patients, with lower grading score (G600000 IU/mL) demonstrated higher expression of HMOX1. In patients with HIV/HCV co-infection, the expression of HMOX1 was lower in patients with lower lymphocyte CD4 count and higher HIV viral load. IL28B polymorphism did not affect the expression of either HMOX1 or miR-122. Higher HMOX1 expression correlated with higher expression of Bach-1 (Spearman's ρ = 0.586, p = 0.000001) and miR-122 (Spearman's ρ = 0.270, p = 0.014059). HMOX1 and miR-122 play an important role in the pathogenesis of CHC in HCV mono-and HIV/HCV co-infected patients. Reduced expression of HMOX1 in patients with HIV/HCV co-infection may indicate a worse prognosis in this group. Our results do not support the importance of Bach-1 in repression of HMOX1 in patients with chronic hepatitis C.

  9. Assessment of hepatic fibrosis by fibroscan in egyptian chronic hemodialysis patients with chronic Hepatitis C (genotype 4: A single-center study

    Directory of Open Access Journals (Sweden)

    Bahaa El-Din Moustafa Zayed

    2017-01-01

    Full Text Available Assessing hepatic fibrosis in hemodialysis patients with chronic hepatitis C (CHC can help to evaluate the long-term prognosis, complications of hepatitis C virus (HCV as well as eligibility for renal transplantation,. Our aim was to assess liver fibrosis in Egyptian hemodialysis (HD patients infected with CHC genotype 4 using a fibroscan. This cross-sectional observational study was conducted over two years on a cohort of 134 Egyptian patients on prevalent HD at Kasr Al Ainy Hospital. All patients were subjected to routine laboratory evaluation including, hepatitis B surface antigen, hepatitis B core antibody, hepatitis Be antigen, hepatitis C antibody (HCVAb and human immunodeficiency virus antibody, quantitative polymerase chain reaction (PCR for both HCV and hepatitis B virus (HBV, serum hyaluronic acid level, and alpha-fetoprotein (AFP. Fibroscan was performed on all HCV-positive patients. The mean age was 47.43 ± 12.65 years, 50.7% were male, and 49.3% were female. The most common causes of end-stage renal disease were hypertensive nephropathy (32.1% and diabetic nephropathy (18.7%. HCVAb was positive in 57.5% of the patients and HBV was positive in 3%. Forty HCV-positive patients (57.1% who underwent fibroscan had mild to significant fibrosis, and thirty patients (42.9% had advanced fibrosis. There was significant correlation between HCV PCR and duration on HD, number of blood transfusions, and hyaluronic acid (HA level. In addition, there was a significant correlation between serum HA and HD duration as well as liver fibrosis. No significant correlation was found between duration on HD and fibrosis stage (P = 0.619; also, no significant correlation was noted between the age of the patients and HA level or stage of fibrosis (P = 0.970. Fibro-scan is a simple noninvasive test that can be used to assess liver fibrosis in HD patients with CHC. Most of the study patients had mild to significant fibrosis.

  10. HCV Co-infection is Associated with Metabolic Abnormalities among ...

    African Journals Online (AJOL)

    Table 3 shows results of simple linear regression of glucose and the cholesterol fractions against HCV co- infection status. HIV/HCV co infection predicted a statistically significant reduction in all the cholesterol containing fractions. No such relationship existed between the HCV co infection and glucose or triglycerides. The.

  11. School adolescents’ knowledge concerning hepatitis C virus (HCV

    Directory of Open Access Journals (Sweden)

    Lidia Sierpińska

    2017-01-01

    Full Text Available Introduction. Infection with hepatitis C virus (HCV is a serious clinical, epidemiological and social problem inPoland.    Objective. The objective of the study was recognition of knowledge concerning HCV infection among adolescents attending post-secondary schools. Material and method. The study was conducted in 2016, among 106 school adolescents attending two post-secondary schools inRadom, by means of a questionnaire designed by the author and a standardized questionnaire according to the Polish Group of HCV Experts. Statistical analysis was performed using the software Statistica 10.0. Results. The majority of adolescents (84.5% knew that HCV causes hepatitis C.  Boys more frequently than girls knew that the disease spreads by contact with infected blood (72.0% and 50.6%, respectively. Girls significantly more often than boys knew that approximately 700,000 people inPoland are infected with HCV (54.3% and 24.0%, respectively. According to 84.1% of respondents everyone is exposed to this infection.  Boys more often than girls (72.0% and 55.6% correctly provided examples of situations in which the infection may occur. The majority of adolescents (88.5% knew that the hepatitis C antibody (anti-HCV blood test indicates whether the person has an infection. A half of the examined adolescents (50.9% knew that there is currently no vaccine available to protect against hepatitis C, and that it is possible to cure the person infected with HCV. Conclusions. The level of adolescents’ knowledge concerning HCV infection varied according to the demographic and social factors. School adolescents should be provided incentives for prophylaxis of infection and participation in prophylactic programmes, in order to limit the risk of contracting hepatitis C.

  12. Alterations in microRNA expression profile in HCV-infected hepatoma cells: Involvement of miR-491 in regulation of HCV replication via the PI3 kinase/Akt pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Hisashi; Tatsumi, Tomohide; Hosui, Atsushi; Nawa, Takatoshi; Kodama, Takahiro; Shimizu, Satoshi; Hikita, Hayato; Hiramatsu, Naoki; Kanto, Tatsuya [Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita 565-0871 (Japan); Hayashi, Norio [Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki 660-8511 (Japan); Takehara, Tetsuo, E-mail: takehara@gh.med.osaka-u.ac.jp [Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita 565-0871 (Japan)

    2011-08-19

    Highlights: {yields} HCV infection upregulated miR-192, -194, -215, downregulated miR-320, -491. {yields} Transfection of miR-192, -215, and -491 enhanced HCV replication. {yields} Transfection of miR-491 inhibited Akt phosphorylation. {yields} Akt inhibition could be responsible for augmentation of HCV replication by miR-491. -- Abstract: The aim of this study was to investigate the role of microRNA (miRNA) on hepatitis C virus (HCV) replication in hepatoma cells. Using miRNA array analysis, miR-192/miR-215, miR-194, miR-320, and miR-491 were identified as miRNAs whose expression levels were altered by HCV infection. Among them, miR-192/miR-215 and miR-491 were capable of enhancing replication of the HCV replicon as well as HCV itself. HCV IRES activity or cell proliferation was not increased by forced expression of miR-192/miR-215 or miR-491. Investigation of signaling pathways revealed that miR-491 specifically suppressed the phosphoinositol-3 (PI3) kinase/Akt pathway. Under inhibition of PI3 kinase by LY294002, the suppressive effect of miR-491 on HCV replication was abolished, indicating that suppression of HCV replication by miR-491 was dependent on the PI3 kinase/Akt pathway. miRNAs altered by HCV infection would then affect HCV replication, which implies a complicated mechanism for regulating HCV replication. HCV-induced miRNA may be involved in changes in cellular properties including hepatocarcinogenesis.

  13. Acetaminophen-induced acute liver injury in HCV transgenic mice

    International Nuclear Information System (INIS)

    Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U.; Tech, Katherine; Macdonald, Jeffrey M.; Boorman, Gary A.; Chatterjee, Saurabh; Mason, Ronald P.; Melnyk, Stepan B.; Tryndyak, Volodymyr P.; Pogribny, Igor P.; Rusyn, Ivan

    2013-01-01

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  14. Acetaminophen-induced acute liver injury in HCV transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U. [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Tech, Katherine; Macdonald, Jeffrey M. [Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Boorman, Gary A. [Covance, Chantilly, VA 20151 (United States); Chatterjee, Saurabh; Mason, Ronald P. [Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, RTP, NC 27713 (United States); Melnyk, Stepan B. [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72201 (United States); Tryndyak, Volodymyr P.; Pogribny, Igor P. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Rusyn, Ivan, E-mail: iir@unc.edu [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States)

    2013-01-15

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  15. Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitors

    Directory of Open Access Journals (Sweden)

    Luciana Bonome Zeminian

    2013-02-01

    Full Text Available The goal of treatment of chronic hepatitis C is to achieve a sustained virological response, which is defined as exhibiting undetectable hepatitis C virus (HCV RNA levels in serum following therapy for at least six months. However, the current treatment is only effective in 50% of patients infected with HCV genotype 1, the most prevalent genotype in Brazil. Inhibitors of the serine protease non-structural protein 3 (NS3 have therefore been developed to improve the responses of HCV-infected patients. However, the emergence of drug-resistant variants has been the major obstacle to therapeutic success. The goal of this study was to evaluate the presence of resistance mutations and genetic polymorphisms in the NS3 genomic region of HCV from 37 patients infected with HCV genotype 1 had not been treated with protease inhibitors. Plasma viral RNA was used to amplify and sequence the HCV NS3 gene. The results indicate that the catalytic triad is conserved. A large number of substitutions were observed in codons 153, 40 and 91; the resistant variants T54A, T54S, V55A, R155K and A156T were also detected. This study shows that resistance mutations and genetic polymorphisms are present in the NS3 region of HCV in patients who have not been treated with protease inhibitors, data that are important in determining the efficiency of this new class of drugs in Brazil.

  16. Inhibition of HCV replication by oxysterol-binding protein-related protein 4 (ORP4 through interaction with HCV NS5B and alteration of lipid droplet formation.

    Directory of Open Access Journals (Sweden)

    In-Woo Park

    Full Text Available Hepatitis C virus (HCV RNA replication involves complex interactions among the 3'x RNA element within the HCV 3' untranslated region, viral and host proteins. However, many of the host proteins remain unknown. In this study, we devised an RNA affinity chromatography /2D/MASS proteomics strategy and identified nine putative 3' X-associated host proteins; among them is oxysterol-binding protein-related protein 4 (ORP4, a cytoplasmic receptor for oxysterols. We determined the relationship between ORP4 expression and HCV replication. A very low level of constitutive ORP4 expression was detected in hepatocytes. Ectopically expressed ORP4 was detected in the endoplasmic reticulum and inhibited luciferase reporter gene expression in HCV subgenomic replicon cells and HCV core expression in JFH-1-infected cells. Expression of ORP4S, an ORP4 variant that lacked the N-terminal pleckstrin-homology domain but contained the C-terminal oxysterol-binding domain also inhibited HCV replication, pointing to an important role of the oxysterol-binding domain in ORP4-mediated inhibition of HCV replication. ORP4 was found to associate with HCV NS5B and its expression led to inhibition of the NS5B activity. ORP4 expression had little effect on intracellular lipid synthesis and secretion, but it induced lipid droplet formation in the context of HCV replication. Taken together, these results demonstrate that ORP4 is a negative regulator of HCV replication, likely via interaction with HCV NS5B in the replication complex and regulation of intracellular lipid homeostasis. This work supports the important role of lipids and their metabolism in HCV replication and pathogenesis.

  17. Insulin resistance and response to telaprevir plus peginterferon alpha and ribavirin in treatment-naive patients infected with HCV genotype 1

    NARCIS (Netherlands)

    Serfaty, L.; Forns, X.; Goeser, T.; Ferenci, P.; Nevens, F.; Carosi, G.; Drenth, J.P.H.; Lonjon-Domanec, I.; DeMasi, R.; Picchio, G.; Beumont, M.; Marcellin, P.

    2012-01-01

    OBJECTIVE: Insulin resistance is a predictor of poor response to peginterferon/ribavirin in patients infected with the chronic hepatitis C virus (HCV). There are no data on direct-acting antivirals. This exploratory analysis assessed the effect of metabolic factors and insulin resistance, measured

  18. Prevalence of High-Risk Genotypes of Human Papillomavirus: Women Diagnosed with Premalignant and Malignant Pap Smear Tests in Southern Ecuador

    Science.gov (United States)

    Loján González, Cisne; Córdova Rodríguez, Ana; Acurio Páez, Katherine; Arévalo, Ana Paulina; Bobokova, Jana

    2017-01-01

    Human papillomavirus (HPV) is the primary infectious agent for the development of cervical cancer, although the presence of the virus alone is insufficient for viral development and proliferation; this can be attributed to the increase in potential oncogenic risk, along with other risk factors. In the present investigation, the prevalence of high-risk HPV was determined from samples of premalignant or malignant cervical cytology in women from the southern region of Ecuador. The kit we used was able to detect genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. In addition, 64.5% of the analyzed samples were positive for HPV, with genotypes 16 and 18 being the most prevalent (16 was detected in 148 samples and 18 in 108). Genotypes 58 and 51 were the third most frequent simple and multiple infections, respectively. The data are very similar to those obtained worldwide, suggesting that the strategy of sex education, and the use of vaccines as primary prevention agents, could significantly decrease the incidence and mortality rate of cervical cancer in the southern region of Ecuador. PMID:28717342

  19. Assessment of hepatitis C virus infection in two adjacent Thai provinces with drastically different seroprevalence.

    Directory of Open Access Journals (Sweden)

    Rujipat Wasitthankasem

    Full Text Available Improved awareness of the hepatitis C virus (HCV transmission has contributed to the overall decline in the HCV infection rate in some developing countries including Thailand. Chronic HCV infection in some rural Thai communities, however, presents a challenge in the efforts to treat and manage HCV-related diseases. Published and unpublished studies have suggested an unusually high incidence of HCV infection in a Thai province of Phetchabun compared to elsewhere in Thailand. To determine the magnitude of HCV infection and identify potential factors contributing to the higher rate of HCV infection in this province, we performed a population-based study in Phetchabun (n = 1667 and the neighboring Khon Kaen province (n = 1410 where HCV prevalence is much lower. Individuals between 30 and 64 years old completed detailed questionnaires designed to identify HCV risk factors and provided blood samples for anti-HCV antibody screening. The anti-HCV seropositive rates were 15.5% (259/1667 in Phetchabun and 3.6% (51/1410 in Khon Kaen. Positive samples were subsequently genotyped for HCV core gene sequence and assessed for the hepatitis B virus surface antigen (HBsAg and human immunodeficiency virus antigen/antibody (HIV Ag/Ab. More individuals in Phetchabun possessed the combined presence of HBsAg (5.0% and HIV Ag/Ab (0.4% than those in Khon Kaen (3.9% HBsAg and 0.0% HIV Ag/Ab. While male gender, intravenous drug use (IVDU and tattoos were significant HCV risk factors in both provinces (p <0.05, education less than high school and agriculture-related occupation were additionally associated with HCV in Phetchabun. HCV genotypes 6, 3, and 1 were identified in similar frequency in both provinces. We estimated that prevalence of HCV seropositivity and viremic carriers were higher in Phetchabun (143 and 111 per 1000 than in Khon Kaen (34 and 22 per 1000. Finally, we derived a simple risk factor-based scoring system as a useful preclinical tool to screen

  20. Alcohol and HCV Chronic Infection Are Risk Cofactors of Type 2 Diabetes Mellitus for Hepatocellular Carcinoma in Italy

    Directory of Open Access Journals (Sweden)

    Massimiliano Balbi

    2010-03-01

    Full Text Available Type 2 diabetes mellitus (DM2 has been associated with hepatocellular carcinoma (HCC development. To study this relationship, we enrolled 465 HCC patients compared with 618 Cirrhotic cases and 490 Controls. The prevalence of DM2 is significantly higher in HCC patients with an Odds Ratio of 3.12 versus Controls. In HCC cases with alcohol abuse, the frequency of DM2 is the highest. In our HCC patients, when HCV infection is associated with alcohol abuse, the liver cancer develops earlier. In addition, multivariate analysis shows that alcohol consumption is an independent risk factor for HCC more relevant than HCV infection.