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  1. Survey of US Correctional Institutions for Routine HCV Testing

    OpenAIRE

    Beckwith, Curt G.; Kurth, Ann E.; Bazerman, Lauri; Solomon, Liza; Patry, Emily; Rich, Josiah D.; Kuo, Irene

    2015-01-01

    To ascertain HCV testing practices among US prisons and jails, we conducted a survey study in 2012, consisting of medical directors of all US state prisons and 40 of the largest US jails, that demonstrated a minority of US prisons and jails conduct routine HCV testing. Routine voluntary HCV testing in correctional facilities is urgently needed to increase diagnosis, enable risk-reduction counseling and preventive health care, and facilitate evaluation for antiviral treatment.

  2. Survey of US Correctional Institutions for Routine HCV Testing.

    Science.gov (United States)

    Beckwith, Curt G; Kurth, Ann E; Bazerman, Lauri; Solomon, Liza; Patry, Emily; Rich, Josiah D; Kuo, Irene

    2015-01-01

    To ascertain HCV testing practices among US prisons and jails, we conducted a survey study in 2012, consisting of medical directors of all US state prisons and 40 of the largest US jails, that demonstrated a minority of US prisons and jails conduct routine HCV testing. Routine voluntary HCV testing in correctional facilities is urgently needed to increase diagnosis, enable risk-reduction counseling and preventive health care, and facilitate evaluation for antiviral treatment. PMID:25393180

  3. Single Clinical Practice's Report of Testing Initiation, Antibody Clearance, and Transmission of Hepatitis C Virus (HCV) in Infants of Chronically HCV-Infected Mothers.

    Science.gov (United States)

    Bal, Aswine; Petrova, Anna

    2016-01-01

    Background.  Perinatally acquired hepatitis C virus (HCV) is the main source of pediatric HCV infection. However, the best time for initiation of screening and follow up of these infants is still unknown. Analysis of the clinical data of infants born to HCV-infected mothers, transmission rates, and pathway of HCV testing could be important for optimization of their management. Methods.  Children of mothers with chronic HCV infection, who were observed between 1998 and 2013 at the pediatric infectious disease clinic for the first 18 months of their life, were eligible for enrollment. We analyzed the factors influencing initiation of HCV testing in these children and rate of HCV transmission as demonstrated by consecutive HCV antibody and HCV ribonucleic acid (RNA) amplification testing. Results.  One hundred and forty-two mother-infant pairs were enrolled. The majority of mothers were intravenous drug users, had carried to term, and delivered vaginally. A high proportion of infants had at least 1 positive anti-HCV antibody assay without viremia. True HCV infection and intermittent viremia were recorded in 3.5% and 1.4% of infants, respectively. Initiation of HCV testing after 10 months of age was associated with a significant decline in the probability of obtaining a positive HCV antibody of maternal origin. Conclusions.  The low likelihood for detection and confirmation of true HCV transmission before 10 months of age could challenge the early initiation of HCV screening of infants exposed to maternal HCV infection but may affect the parental need for early monitoring and counseling. PMID:26985444

  4. Hepatitis C Virus Serologic and Virologic Tests and Clinical Diagnosis of HCV-Related Liver Disease

    Directory of Open Access Journals (Sweden)

    2006-04-01

    Full Text Available The use of serological and virological tests has become essential in the management of hepatitis C virus (HCV infection in order to diagnose infection, guide treatment decisions and assess the virological response to antiviral therapy. Virological tools include serological assays for anti-HCV antibody detection and serological determination of the HCV genotype, and molecular assays that detect and quantify HCV RNA and determine the HCV genotype. Anti-HCV antibody testing and HCV RNA testing are used to diagnose acute and chronic hepatitis C. Only patients with detectable HCV RNA should be considered for pegylated interferon alfa and ribavirin therapy and the HCV genotype should be systematically determined before treatment, as it determines the indication, the duration of treatment, the dose of ribavirin and the virological monitoring procedure. HCV RNA monitoring during therapy is used to tailor treatment duration in HCV genotype 1 infection, and molecular assays are used to assess the end-of-treatment and, most importantly the sustained virological response, i.e. the endpoint of therapy.

  5. Prevalence of active HCV infection among the blood donors of Khyber Pakhtunkwa and FATA region of Pakistan and evaluation of the screening tests for anti-HCV

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    Khan Sanaullah

    2011-04-01

    Full Text Available Abstract Hepatitis C is a fatal liver disease caused by the hepatitis C virus. In this study, blood donors, from various districts of the KPK province and the federally administered tribal area (FATA of Pakistan were tested for anti-HCV antibodies and HCV RNA by ICT (Immuno-chromatographic test, ELISA and RT-PCR. Out of the 7148 blood donors, 224 (3.13% were positive for anti-HCV antibodies by ICT, 135 (1.89% by ELISA while 118 (1.65% blood donors had active HCV infection as detected by RT-PCR. We suggest that ELISA should be used for anti-HCV screening in public sector hospitals and health care units.

  6. [Advanced Testing and Laboratory for HBV, HCV, and HIV Infection].

    Science.gov (United States)

    Deguchi, Matsuo

    2015-06-01

    Most target substances for immunoassay of infectious disease are antigens or antibodies which do not exist in the human body. Therefore, the method to set reference values is different from chemistry or hematology testing. High sensitivity is required for infectious disease testing, particularly for screening. Also, its reference values (cut-off values) are set as low as possible. Therefore, a false-positive reaction can be caused due to slightly non-specific reactions in infectious disease reagents. The specificities for infectious disease reagents were evaluated with 9 kinds of HCV antibody test kit and 9 kinds of HIV screening kit. The frequencies of false-positive results were 0.2-1.8 and 0.2-1.3%, respectively, and even a kit with a high specificity showed a false-positive result for 1 in 500 samples. The sensitivities for infectious disease reagents were evaluated with a newly developed super-high- sensitive HBs antigen assay kit and 8 kinds of chemiluminescence HBs antigen assay kit which are highly sensitive conventional kits. As a result, the super-high-sensitive kit was 10 to 40 times more sensitive than conventional kits. After introducing the super-high-sensitive kit to routine assays, 16 HBV-infected patients, who were not identified with the conventional kits, were detected for six months. On the other hand, we confirmed false-positive results due to contamination between specimens after introducing the super-high-sensitive kit. It is recommended to use the super-high-sensitive kit in a well-controlled environment to prevent contamination between specimens in order to generate highly reliable test results. PMID:26548240

  7. Seroprevalence of HCV and HIV Infections by Year of Birth in Spain: Impact of US CDC and USPSTF Recommendations for HCV and HIV Testing

    Science.gov (United States)

    Meijide, Héctor; Cañizares, Angelina; Castro-Iglesias, Ángeles; Delgado, Manuel; Pértega, Sonia; Pedreira, José; Bou, Germán; Poveda, Eva

    2014-01-01

    Background The US Centers for Disease Control and Prevention (CDC) recently add the advice of one-time testing of HCV infection in persons born during 1945–1965. Moreover, the US Preventive Services Task Force (USPSTF) newly recommended one-time HIV testing for persons aged 15–65. Herein, we evaluate the potential impact of these recommendations in a reference medical area of Spain. Methods All assays results entries for HCV and HIV serological markers ordered at a reference lab from primary care and specialized physicians between 2008 and 2012 were recorded in a medical area which covers 501,526 citizens in Northern Spain. The year of birth were also documented. Results A total of 108,159 anti-HCV-Ab results were generated during the study period. The global rate of anti-HCV-Ab+ was 7.7% (95% CI: 7.6%–7.9%), being more prevalent in men than women (8.6% vs. 4.5%). By year of birth, the highest prevalence was found in persons born between 1955 and 1970. HCV genotype 1 was the most prevalent (59.7%) followed by genotype 3 (22.7%). Regard HIV infection, among 65,279 anti-HIV results generated the prevalence of anti-HIV+ was 1.1% (95% CI: 1.0%–1.2%), being more frequent in men (2% vs 0.5%). The years of birth with highest rates of HIV infection exactly match with those for HCV infection. Conclusions The highest rates of HCV and HIV infections are found between 1960 and 1965. Different historical and social circumstances such as the huge intravenous drug use epidemic in the eighties in Spain, might explain it. Therefore, each country needs to determine its own HCV and HIV seroprevalences by year of birth to establish the proper recommendations for the screening of both infections. PMID:25436642

  8. Incidence of recent HCV infection among persons seeking voluntary counselling and testing for HIV and sexually transmitted infections in Taiwan

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    Yi-Ching Su

    2014-11-01

    Full Text Available Introduction: The incidence of recent hepatitis C virus infection (HCV infection has been noted to be increasing among men who have sex with men (MSM, especially those with HIV infection, in several resource-rich settings. In Taiwan, the incidence of recent HCV infection increased from 0 in 1994–2000, 2.29 in 2001–2005 to 10.13 per 1000 person-years of follow-up (PYFU in 2006–2010. In this study, we aimed to estimate the incidence rate of recent HCV infection among those individuals who sought voluntary counselling and testing (VCT service at a University Hospital. Methods: Between May 2006 and December 2013, 18,246 tests for HIV antibody were performed among 12,143 individuals at the VCT services. A total of 2157 clients without HIV or HCV infection at baseline were included for estimation of incidence rate of recent HCV infection. Antibodies to HCV were determined with a third-generation enzyme immunoassay. A nested case-control study with four matched controls without HCV seroconversion for one HCV seroconverter was conducted to investigate the factors associated with recent HCV infection. Phylogenetic analysis was performed among the HCV strains obtained from VCT clients and patients coinfected with HIV and HCV between 2006 and 2013. Results: During the study period, 2157 clients received a total of 8260 tests. The HCV seroprevalence at baseline was 0.3%. Of the 2150 HCV-negative clients who contributed 5074.99 PYFU, 17 developed HCV seroconversion (incidence rate, 3.35 per 1000 PYFU; 95% CI, 1.76–4.94; the rate increased from 2.28 per 1000 PYFU (95% CI, 0.05–4.51 in 2006–2009, to 3.33 per 1000 PYFU (95% CI, 0.86–5.80 in 2010–2011, to 4.94 per 1000 PYFU (95% CI, 0.99–8.99 in 2012–2013. In case-control study, HCV seroconverters were more likely to have HIV-infected partners, recent syphilis and a Rapid Plasma Reagin (RPR titre of 4 or greater. In multivariate analysis, having HIV-infected partners remained as the only

  9. [Human immunodeficiency virus (HIV) and Hepatitis C virus (HCV) testing among injecting drug users].

    Science.gov (United States)

    Gyarmathy, V Anna; Rácz, József

    2011-01-23

    In Hungary, there is a need for widely accessible HIV and HCV testing and counseling for injecting drug users. Theoretically, free and confidential rapid HIV and HCV testing would be the most suitable for this purpose. Low threshold agencies, such as needle and syringe programs, would provide ideal premises for such a testing system, Here, participants would be able to undergo regular testing every six months. Making rapid testing widely available raises the following three main issues: 1. validity of the testing results (or: the verification of positive rapid test results), 2. circumstances of taking blood (or: legislation regarding drawing blood), and 3. cost effectiveness (or: how important is it to prevent an HIV epidemic). The authors propose the establishment of a system that offers screening using rapid tests and which would be an expansion of a currently existing system of HIV and HCV testing based on finger prick blood. The current system would thus serve as a means to verify the results of the rapid tests. At the same time, there is a need to obtain permission from a public health body to enable in needle and syringe programs the provision of rapid testing and testing of blood using finger pricks. In many countries, test results are given to injecting drug users not by doctors but by trained social workers - such a system could also be established in Hungary. If preventing an HIV epidemic in Hungary is a priority, then wide access to rapid HIV testing is justified. Widely accessible free and confidential rapid HIV and HCV testing and counseling - combined with screening and verification using finger prick blood - may function not only as a testing and counseling service but also as a good quality public health monitoring system. Such a system, however, requires regular financial support from the government. PMID:21224188

  10. Sensitivity and specificity of point-of-care rapid combination syphilis-HIV-HCV tests.

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    Kristen L Hess

    Full Text Available New rapid point-of-care (POC tests are being developed that would offer the opportunity to increase screening and treatment of several infections, including syphilis. This study evaluated three of these new rapid POC tests at a site in Southern California.Participants were recruited from a testing center in Long Beach, California. A whole blood specimen was used to evaluate the performance of the Dual Path Platform (DPP Syphilis Screen & Confirm, DPP HIV-Syphilis, and DPP HIV-HCV-Syphilis rapid tests. The gold-standard comparisons were Treponema pallidum passive particle agglutination (TPPA, rapid plasma reagin (RPR, HCV enzyme immunoassay (EIA, and HIV-1/2 EIA.A total of 948 whole blood specimens were analyzed in this study. The sensitivity of the HIV tests ranged from 95.7-100% and the specificity was 99.7-100%. The sensitivity and specificity of the HCV test were 91.8% and 99.3%, respectively. The treponemal-test sensitivity when compared to TPPA ranged from 44.0-52.7% and specificity was 98.7-99.6%. The non-treponemal test sensitivity and specificity when compared to RPR was 47.8% and 98.9%, respectively. The sensitivity of the Screen & Confirm test improved to 90.0% when cases who were both treponemal and nontreponemal positive were compared to TPPA+/RPR ≥ 1 ∶ 8.The HIV and HCV on the multi-infection tests showed good performance, but the treponemal and nontreponemal tests had low sensitivity. These results could be due to a low prevalence of active syphilis in the sample population because the sensitivity improved when the gold standard was limited to those more likely to be active cases. Further evaluation of the new syphilis POC tests is required before implementation into testing programs.

  11. Evaluation of HBsAg, anti-HCV, anti-HIV and VDRL test results in blood donors

    OpenAIRE

    Deveci, Özcan; Tekin, Alicem; Günbay, Seda Sibel; Kılıç, Dilek; KAYGUSUZ, Sedat; Ağalar, Canan; Özer, Türkan Toka

    2011-01-01

    Objectives: The most frequently encountered complication in the transfusion of blood and blood products are transmitted infections from these products. Infections caused by hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) remain the leading most important health problems in the transfusion of blood and blood products worldwide. Therefore, screening tests such as HBsAg, anti-HCV, anti-HIV, and RPR or VDRL for Treponema pallidum are mandatory tests to loo...

  12. The molecular mimicry and its possible role in origin of false-positive results in HCV-infection testing

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    Benkovskaya L. K.

    2013-09-01

    Full Text Available The main reason for the false positive results of the detection of antibodies to HCV is considered the unspecific binding of the blood serum immunoglobulins with the components of the test-systems’ immunosorbent, what is observed in various pathologies. When considering the issues of diagnosis, prevention and treatment of infectious diseases examined the impact of antigenic heterogeneity and molecular mimicry. With regarding to hepatitis C this phenomenon more illustrated in terms of pathogenesis, autoimmune, extrahepatic lesions. This does not exclude the influence of antigenic mimicry on the specificity of serological tests for anti-HCV detection. Aim. Estimation the frequency of false-positive reactions of anti-HCV testing in patients with chronic somatic diseases and assessment of the antigenic mimicry’s role in their occurrence. Methods. Total anti-HCV, antibodies to the single viruses’ protein, and false positive sera antibodies’ interaction with microbial origin combinations (mimicrins were determined by ELISA. Mimicrins were separated from the cultural medium after cultivation Staphylococcus aureus, Micobacterium tuberculosis and Candida albicans. Results. Upon detection of anti-HCV in patients with chronic pathologies detected a significant number of false-positive results are more likely in patients with diabetes and among healthy individuals – in pregnant women.The majorities of false positive sera interacted with mimicrins. Conclusions. The antigenic crossings over between mimicrins and antibodies in the structure of false positive sera must be considered during the evaluation of the specific diagnostics’ results in the persons with different pathologic states.

  13. Performance of the New Aptima HCV Quant Dx Assay in Comparison to the Cobas TaqMan HCV2 Test for Use with the High Pure System in Detection and Quantification of Hepatitis C Virus RNA in Plasma or Serum.

    Science.gov (United States)

    Schalasta, Gunnar; Speicher, Andrea; Börner, Anna; Enders, Martin

    2016-04-01

    Quantitating the level of hepatitis C virus (HCV) RNA is the standard of care for monitoring HCV-infected patients during treatment. The performances of commercially available assays differ for precision, limit of detection, and limit of quantitation (LOQ). Here, we compare the performance of the Hologic Aptima HCV Quant Dx assay (Aptima) to that of the Roche Cobas TaqMan HCV test, version 2.0, using the High Pure system (HPS/CTM), considered a reference assay since it has been used in trials defining clinical decision points in patient care. The assays' performance characteristics were assessed using HCV RNA reference panels and plasma/serum from chronically HCV-infected patients. The agreement between the assays for the 3 reference panels was good, with a difference in quantitation values of 0.99). The assays had similar levels of total and intra-assay variability across all genotypes at concentrations from 1,000 to 25 IU/ml. Aptima had a greater analytical sensitivity, quantitating more than 50% of replicates at 25-IU/ml target. Aptima showed performance characteristics comparable to those of HPS/CTM and increased sensitivity, making it suitable for use as a clinical diagnostic tool on the fully automated Panther platform. PMID:26865682

  14. Is HCV core antigen a reliable marker of viral load? An evaluation of HCV core antigen automated immunoassay

    OpenAIRE

    Hadziyannis, Emilia; Minopetrou, Martha; Georgiou, Anastasia; Spanou, Fotini; Koskinas, John

    2013-01-01

    Background Hepatitis C viral (HCV) load detection and quantification is routinely accomplished by HCV RNA measurement, an expensive but essential test, both for the diagnosis and treatment of chronic hepatitis C (CHC). HCV core antigen (Ag) testing has been suggested as an attractive alternative to molecular diagnostics. The aim of the study was to evaluate an automated chemiluminescent immunoassay (CLIA) for HCV core Ag measurement in comparison to quantitative HCV RNA determination. Methods...

  15. Incidence of recent HCV infection among persons seeking voluntary counselling and testing for HIV and sexually transmitted infections in Taiwan

    OpenAIRE

    Yi-Ching Su; Wen-Chun Liu; Lan-Hsin Chang; Pei-Ying Wu; Yu-Zhen Luo; Cheng-Hsin Wu; Hsin-Yun Sun; Sui-Yuan Chang; Chien-Ching Hung

    2014-01-01

    Introduction: The incidence of recent hepatitis C virus infection (HCV) infection has been noted to be increasing among men who have sex with men (MSM), especially those with HIV infection, in several resource-rich settings. In Taiwan, the incidence of recent HCV infection increased from 0 in 1994–2000, 2.29 in 2001–2005 to 10.13 per 1000 person-years of follow-up (PYFU) in 2006–2010. In this study, we aimed to estimate the incidence rate of recent HCV infection among those individuals who so...

  16. PML tumor suppressor protein is required for HCV production

    International Nuclear Information System (INIS)

    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.

  17. Rheumatoid Case with HCV Infection

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    Bita Behnava

    2005-03-01

    Full Text Available 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 phosphatase 210, PT 13 second, total protein 7.2 g/dl, albumin 4 g/dl, gama globulin 1.6 g/dl, HBsAg negative and RF positive. She had a history of symmetrical polyarthritis of small joints of upper extremities and morning stiffness for 3 years ago and had been managed as rheumatoid arthritis (RA since then. She was managed with corticosteroids and methotrexate. Are there any relations between RA disease and HCV infection?HCV-related ArthritisRheumatologic complications of HCV infection are common and include mixedcryoglobulinemia, vasculitis, Sjogren’s syndrome, arthritis and fibromyalgia(1, 2. There is a welldefined picture of arthritis associated with the presence of mixed cryoglobulinemia that consists of an intermittent mono or oligoarticular,nondestructive arthritis affecting large and mediumsize joints(1. 2% to 20% of HCV-infected patients experience arthritis and as 50% experience arthralgia(3Clinical ManifestationsHCV-related arthritis (HCVra commonly presents as rheumatoid-like, symmetrical inflammatory polyarthritis involving mainly small joints or less commonly as mono- or oligoarthritis of large joints. The joints involved in HCV-related arthritis are similar to RA(4. In about two thirds of the affected individuals, morning stiffness may be severe, resolving after more than an hour(5. Clinical picture of arthritis associated with the presence of mixed cryoglobulinemia in patients with HCV infection consists of an intermittent, mono or

  18. Occult HCV in Egyptian volunteer blood donors

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    Mostafa A. Amin 1, Kouka S. E. Abdel-Wahab 2 and Adel A.

    2013-01-01

    Full Text Available Objective: The study aims to investigate the risk of post-transfusion transmission of hepatitis c virus (HCV in the circumstances of occult HCV when anti-HCV is undetectable by ELISA and HCV-RNA is detected by RT-PCR in the plasma and or in peripheral blood mononuclear cells (PBMCs of donor blood and the recipients are immunocompromised. Patients & methods: The study covered 18 chronic renal failure patients (CRF [12 males (66.7% their age ranged from 28 to 65 years and 6 females (33.3 % their age ranged from 15 to 55 years] undergoing hemodialysis in Nile Hospital as part of their therapy have to receive blood transfusions (275 blood units for the first time. Commercial ELISA kits for anti-HCV and nested-RT-PCR (N-RT-PCR kits were used. Results: Anti-HCV was positive in one serum from the eighteen (5.5% poly transfused CRF patients at the end of the study while the seventeen sera were negative. This serum was also positive for HCV RNA by N-RT-PCR. Out of the 20 transfused blood units, one blood unit (three components were tested by blood banking anti-HCV negative by ELISA, were positive for HCV RNA by N-RT-PCR. The collective markers of this blood unit represent an occult HCV. The risk of acquiring post-transfusion HCV infection from an occult HCV blood unit is 5%. Real time PCR showed variation in the viral load of the serum of the infected CRF patient, the plasma of blood unit, the PBMCs of this blood unit whether activated by PHA-M or not.

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

    DEFF Research Database (Denmark)

    Soriano, Vincent; Mocroft, Amanda; Rockstroh, Juergen;

    2008-01-01

    , respectively. A greater HCV RNA level was associated with a greater chance of being infected with HCV genotype 1 (aOR, 1.60 per 1 log higher [95% CI, 1.36-1.88]). CONCLUSIONS: More than three-quarters of the HIV- and HCV Ab-positive patients in EuroSIDA showed active HCV replication. Viremia was more frequent......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...... antibody (Ab)-positive patients with HIV infection in the EuroSIDA cohort who had stored samples were tested for serum HCV RNA, and HCV genotyping was done for subjects with viremia. Logistic regression was used to identify variables associated with spontaneous HCV clearance and HCV genotype 1. RESULTS: Of...

  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...... RNA during follow-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.......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...... clearance in the EuroSIDA cohort. METHODS: All HIV-infected patients with documented prior spontaneous HCV clearance, and at least one subsequently collected plasma sample, were examined. The last sample was tested for HCV RNA and those with HCV RNA ≥ 615 IU/mL were defined as having HCV recurrence and...

  1. Analysis of primary carcinoma of the liver of two semi hepatitis B and anti-HCV test results%探析原发性肝癌乙肝两对半及抗-HCV检测结果

    Institute of Scientific and Technical Information of China (English)

    任爱英

    2015-01-01

    目的:对原发性的肝癌乙肝两对半和抗-HCV 的检测结果进行临床分析,探讨乙型肝炎(HBV)和丙型肝炎(HCV)的感染模式和原发性肝癌之间的关系。方法:收治原发性的肝癌乙肝患者130例,于早晨抽取患者空腹静脉血5 mL,并采用酶联免疫法对乙肝两对半和抗-HCV 进行检测,观察检测结果。结果:130例患者中,HBV 的感染率96.15%(112/130),HCV 的感染率16.92%(22/130),HBV 与 HCV 的双重感染率10.77%(14/130)。结论:HBV 的感染很有可能是造成原发性的肝癌发生的主要因素,并对于HBV和HCV的双重感染也必须加以重视。%Objective:To analyze the primary carcinoma of the liver of two semi hepatitis B and anti -HCV test results,discussing the relationship between infection mode of Hepatitis B virus(HBV)and hepatitis C virus(HCV)and the primary hepatocellular carcinoma.Methods:130 patients with primary liver cancer Hepatitis B were selected,in the morning drawing fasting blood 5 mL, and using ELISA for hepatitis B two pairs of semi-detection and anti-HCV,observing the test results.Results:Among the 130 patients,HBV infection rate of 96.15%(112/130),HCV infection rate of 16.92%(22/130) HBV and HCV double infection rate of 10.77%(14/130).Conclusion:HBV infection is likely to be the main factors contributing to the occurrence of primary liver cancer, and for HBV and HCV co-infection must also be valued.

  2. Genotyping Pattern Among Iranian HCV Positive Patients

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    A Sarafnejad

    2010-06-01

    Full Text Available Background: Successful treatment to eliminate HCV RNA depends on the identified genotype. In the present study, we compared the frequency of different HCV genotypes, during four years study (2004 till 2008.Methods: Sera specimens were received from 16 provinces of Iran. We used High Pure Viral Nucleic Acid Purification kit for extraction and samples were tested with improved form of RT-PCR technique. HCV genotypes were determined using Amplisense PCR kit and Amplicor HCV Monitoring Version 2 test utilized a reverse transcription (RT-PCR approach to quantitative HCV RNA. Two hundreds six HCV positive specimens were entered to the study out of 389 tested samples.Results: Type 3a was the most frequent type (46.6%, followed by type 1 (including 1a and 1b with 25.73% and 17.47% for each respectively with 43.2%. Looking through collected results of the four years study confirmed the rate of HCV infection in those single genotypes 1b, 3a were slightly increased from 12.22% and 38.88% in the first year to 18.66 and 46.51% in the fourth year of the study period.Conclusion: The analyzed data proved that some patients were infected with two different types. High viral load was also more correlated to genotype 1 than other types.

  3. HIV, HCV & Leprosy co-infection.

    Science.gov (United States)

    George, A; Kanish, B

    2014-01-01

    In the era where Hansen's disease has achieved elimination status in India, co-infection with HIV can possibly cause a resurgence of this disease. A young intravenous drug abuser was found to have triple affliction, where HIV and HCV infection were discovered on testing after the patient was clinically diagnosed to have Hansen's disease. To our knowledge, there has been no case reported where leprosy was seen with HIV and HCV infection. We are reporting a patient with lepromatous Hansen's disease in type 2 reaction in whom HIV and HCV was incidentally diagnosed. PMID:26118224

  4. The HCV care continuum among people who use drugs: protocol for a systematic review and meta-analysis

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    Reed, Jennifer R.; Jordan, Ashly E.; Perlman, David C.; Smith, Daniel J; Hagan, Holly

    2016-01-01

    Introduction The diagnosis, management, and treatment for hepatitis C virus (HCV) infection (the “HCV care continuum”) have improved in recent years. People who use drugs (PWUD) have a prevalence of HCV infection from 30 to 70 %, yet rates of testing, engagement in care, and treatment for HCV are disproportionately low compared to other populations. Delineating the progression of PWUD through the steps in the HCV care continuum in the USA is important in informing efforts to improve HCV outco...

  5. [Investigation of the correlation between anti-HCV levels (S/Co) with HCV-RNA in the diagnosis of hepatitis C virus (HCV) infection].

    Science.gov (United States)

    Şanlıdağ, Tamer; Akçalı, Sinem; Ecemiş, Talat; Süer, Kaya; Erbay Dündar, Pınar; Arıkan, Ayşe; Güvenir, Meryem; Güler, Emrah

    2016-07-01

    Detection of borderline and/or low positive anti-HCV results by enzyme immunoassay (EIA) leads to severe problems in routine laboratories and needs confirmation with nucleic acid amplification tests which can increase the cost. In EIA tests, if the ratio of sample to cut-off (S/Co) is ≥ 1, the sample is accepted as positive according to the manufacturers' instructions. Although over the last decade the application of S/Co values have also applied to HCV-RNA readings, the current study aims to determine whether the S/Co value is adequate and applicable for the anti-HCV EIA test, and to determine whether a correlation exists between HCV-RNA and HCV infections. A total of 658 cases (402 female, 256 male; mean age: 49.4 ± 17.0 years) who were found anti-HCV positive between January 2011-July 2013 were included in the study. Anti-HCV tests were performed by chemiluminescent EIA (Architect i2000SR, Abbott, USA and LiaisonXL Murex, DiaSorin, Italy) and HCV-RNA by real-time PCR (Cobas Ampliprep/Cobas TaqMan HCV, Roche, USA). The mean S/Co value of the cases was 7.3 ± 4.8 (range: 1.00-17.59) and mean HCV-RNA value was 2.3x105 ± 2.1x106 copies/ml. When the anti-HCV S/Co value of varying ranges was compared with HCV-RNA readings a particular trend was noted. In the anti-HCV S/Co values of 1.0-4.0; 4.1-7.0; 7.1-10.0; 10.1-13.0; 13.1-16.0 and ³16.1, HCV-RNA positivity rates were detected as 1.9%, 24.7%,37.1%, 46.7%, 56.4% and 75%, respectively. Statistical analysis indicated an intermediate positive correlation (r= 0.454) between anti-HCV ve HCV-RNA readings (p= 0.000). An adequate S/Co value was accepted as 5.0 based on the ROC analysis, and this value gave a performance confidence level of 95.6% when determining whether a patient is HCV positive. Based on the data of this study it became evident that further EIA testing is not required if the S/Co value is ≥ 5.0, however if the S/Co value is less than 5.0, then further clinical analysis and revaluation of the patient

  6. Prevalence of hepatitis C virus (HCV coinfection in HIV infected individuals in south India and characterization of HCV genotypes

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    Ponamgi SPD

    2009-01-01

    Full Text Available Purpose: To determine anti-HCV antibodies and genomic subtype of HCV in 1487 confirmed human immunodeficiency virus (HIV positive samples. Methods: A total of 1487 confirmed HIV-positive samples were tested for anti-HCV antibodies by using a third generation ELISA kit (Ortho 3.0 and by RT PCR for HCV. HIV and HCV coinfected samples were selected for HCV genotyping by RFLP and subtyping with NS5-type specific primers. Results: A total of 1487 HIV-infected serum samples were screened for HCV infection, of which, a 1443 (97.04% were negative and 45 (3.02% were coinfected. HIV-HCV coinfection was predominant in the age group 41-50 years (51.1%. HCV genotyping and subtyping was done for the 45 HCV RNA-positive specimens of which genotype 1 was observed in 31 (68.8% and genotype 3 was observed in 14 (31.1% subjects. Further subtyping analysis showed the genotype 1b in 23 (51.1%, 1a in eight (17.7%, 3a in 10 (22.2% and 3b in four (8.8% subjects. Conclusion: HIV and HCV seroprevalence is higher in South India, and the most prevalent genotype in coinfection was genotype 1b.

  7. PML tumor suppressor protein is required for HCV production

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    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.

  8. Anti-HCV prevalence in the general population of Lithuania

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    Liakina, Valentina; Valantinas, Jonas

    2012-01-01

    Summary Background The aim of this study was to assess risk factors for HCV acquisition and prevalence of anti-HCV in the general population of Lithuania. Material/Methods The study enrolled 1528 randomly selected adults from the 5 biggest cities of Lithuania and its rural regions. Screening for anti-HCV was performed by analysis of peripheral capillary blood with lateral flow immunochromatography and confirmation of positive cases by peripheral venous blood testing with 2-step chemiluminescent microparticle immunoassay. Results Anti-HCV prevalence in Lithuania is 2.78% and according to the standard European population the adjusted anti-HCV rate is 2.85%. It is more prevalent among men (crude rates: 4.02% males vs. 1.49% females, p=.0030) and this does not depend on age. Vilnius and Kaunas regions have higher infection rates than smaller rural regions (2.92% and 3.01% vs. 2.24%, 0.74% and 1.35%). Nowadays among our population HCV infection spreads mainly via intravenous drug use (OR=42.5, p<.0001). HCV transmission occurs through blood transfusions (OR=6.4, p=.0002), tooth removal (OR=4.1, p=.0048), childbirth (OR=5.0, p=.0224), multiple and a long-term hospitalization (OR=3.0, p=.0064), tattooing (OR=4.4, p=.0013), open traumas (OR=3.7, p=.0009) and intrafamilially (OR=11.3, p=.0002). Conclusions 2.78% of the population is anti-HCV-positive. The anti-HCV rate is higher in Vilnius and Kaunas in comparison with other regions. HCV spreads mainly through intravenous drug use, but intrafamilial and some nosocomial routes are also important. The anti-HCV prevalence did not depend on age. Despite active prevention of nosocomial HCV transmission, the incidence of HCV infection does not decrease due to virus spread mostly in “trusted networks” of intravenous drug users. PMID:22367136

  9. HCV Transmission between serodiscordant couples through sexual route

    International Nuclear Information System (INIS)

    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

  10. Prevalence of hepatitis C virus (HCV infection and HCV genotypes of hemodialysis patients in Salvador, Northeastern Brazil

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    Silva L.K.

    2006-01-01

    Full Text Available Hepatitis C virus (HCV infection has been identified as the major cause of chronic liver disease among patients on chronic hemodialysis (HD, despite the important reduction in risks obtained by testing candidate blood donors for anti-HCV antibodies and the use of recombinant erythropoietin to treat anemia. A cross-sectional study was performed to estimate the prevalence of HCV infection and genotypes among HD patients in Salvador, Northeastern Brazil. Anti-HCV seroprevalence was determined by ELISA in 1243 HD patients from all ten different dialysis centers of the city. HCV infection was confirmed by RT-PCR and genotyping was performed by restriction fragment length polymorphism. Anti-HCV seroprevalence among HD patients was 10.5% (95% CI: 8.8-12.3 (Murex anti-HCV, Abbott Murex, Chicago, IL, USA. Blood samples for qualitative HCV detection and genotyping were collected from 125/130 seropositive HD patients (96.2%. HCV-RNA was detected in 92/125 (73.6% of the anti-HCV-positive patients. HCV genotype 1 (77.9% was the most prevalent, followed by genotype 3 (10.5% and genotype 2 (4.6%. Mixed infections of genotypes 1 and 3 were found in 7.0% of the total number of patients. The present results indicate a significant decrease in anti-HCV prevalence from 23.8% detected in a study carried out in 1994 to 10.5% in the present study. The HCV genotype distribution was closely similar to that observed in other hemodialysis populations in Brazil, in local candidate blood donors and in other groups at risk of transfusion-transmitted infection.

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

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    Lauren E Kushner

    Full Text Available BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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

  12. Epidemiology of HCV infection.

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    Baldo, V; Baldovin, T; Trivello, R; Floreani, A

    2008-01-01

    It is estimated that approximately 130-170 million people worldwide are infected with hepatitis C virus (HCV). According to data from WHO community and blood donor surveys, the African and Eastern Mediterranean countries report the highest prevalence rates (>10%). The rates of infection in the general population and the incidence of newly-acquired cases indicate an appreciable change in the epidemiology of the infection in recent years. Prior to the widespread screening of blood donations, infected blood and blood products represented a common source of infection. On the other hand, the high peak in HCV antibodies among the elderly in Italian epidemiological studies on the population at large reflects a cohort effect due to an epidemic of HCV infection occurring after the Second World War. According to data reported by the CDC Surveillance System, the incidence of acute hepatitis C has declined since the late 1980s. In 2005, as in previous years, the majority of such cases in North America and Northern Europe occurred among young adults and injected drug use was the most common risk factor. Other, less commonly reported modes of HCV acquisition are occupational exposure to blood, high-risk sexual activity, tattooing, body piercing and other forms of skin penetration. Finally, the overall rate of mother-to-child transmission from HCV-infected, HIV-negative mothers has been estimated at around 5% (coinfection with HIV raises this figure to 19.4%). HCV prevention relies on identifying and counseling uninfected persons at risk of contracting hepatitis C. PMID:18673187

  13. 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.

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

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    Zhifang Jia

    Full Text Available BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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

  15. HCV seropositivity in inmates and in the general population: an averaging approach to establish priority prevention interventions

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    Roux, P; Sagaon-Teyssier, L; C. Lions; Fugon, L.; Verger, P.; Carrieri, M. P.

    2014-01-01

    Objectives Despite the fact that a considerable portion of hepatitis C virus (HCV) positive individuals are viraemic, the risk of transmitting HCV to others is context dependent. Prison is a particularly risky environment as HCV prevention tools are often unavailable. Using data from a cross-sectional study conducted in centres for HCV testing in southeastern France, we aimed to compare the patterns of risk factors in HCV-positive inmates with those in the general population. Setting 26 centr...

  16. The association of syringe type and syringe cleaning with HCV infection among IDUs in Budapest, Hungary.

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    Gyarmathy, V Anna; Neaigus, Alan; Mitchell, Mary M; Ujhelyi, Eszter

    2009-03-01

    We assessed whether syringe type, syringe cleaning and distributive syringe sharing were associated with self-reported and laboratory-confirmed HCV infection among Hungarian IDUs. Injecting drug users (N=215) were recruited from non-treatment settings in Budapest, Hungary between October 2005 and December 2006. Multivariate logistic regression models identified correlates of self-report of being HCV infected and testing positive for HCV. While 37% tested positive for HCV, 14% of the total (39% of those who tested positive) self-reported being HCV infected. Using any two-piece syringes was significantly associated with self-reported HCV infection, while distributive syringe sharing was not associated with self-report of being HCV infected. Engaging in receptive sharing of only one-piece syringes but always cleaning before reuse was not associated with testing HCV positive, while any receptive sharing of only one-piece syringes and not always cleaning before reuse was significantly associated with testing HCV positive. Sharing cookers and squirting drugs from one syringe into another syringe were not associated with testing HCV positive. The high percent of those HCV infected who did not know they were infected highlights the need to provide better access to confidential testing and counseling services. Counseling should emphasize secondary prevention of HCV among HCV infected IDUs. Our findings also indicate that syringe type and syringe cleaning practices may play a role in HCV transmission. Ethnographic research should identify the reasons why IDUs may use two-piece syringes and suggest means to reduce their use. Thorough cleaning of one-piece syringes when sterile syringes are unavailable may be an efficient way to reduce the risk of HCV infection. PMID:19058925

  17. A Practical Approach to Managing Patients with HCV Infection

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    2006-04-01

    Full Text Available Hepatitis C virus (HCV infection is a major worldwide public health concern. It is a common cause of chronic liver disease and hepatocellular carcinoma. HCV antibody and HCV RNA testing are available diagnostic studies that offer high degree of accuracy. Current standard therapy includes a combination of pegylated interferon and ribavirin. Response rate is approximately 40% for genotype 1 and 80% for genotypes 2 and 3, respectively. Successful treatment can stop the progression of chronic liver disease, reduce the need for liver transplantation, and possibly decrease the risk for Hepatocellular carcinoma (HCC. Evaluating for potential treatment candidacy is an important initial step in the management of chronic HCV infection as not all individuals may need or qualify for the treatment. Understanding the natural history, the different diagnostic modalities, the current therapeutic options and, the treatment response and adverse effect profiles can help the practitioners better manage chronic HCV infection.

  18. 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.

  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

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    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)

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

    Science.gov (United States)

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

    2015-01-01

    Objective: 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. Methods: 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. Results: 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. Conclusion: 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. PMID:26649001

  2. Effect of combined siRNA of HCV E2 gene and HCV receptors against HCV

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    Ashfaq Usman Alli A

    2011-06-01

    Full Text Available Abstract Background/Aim Hepatitis C virus (HCV is a major threat as almost 3% of the world's population (350 million individual and 10% of the Pakistani population is chronically infected with this virus. RNA interference (RNAi, a sequence-specific degradation process of RNA, has potential to be used as a powerful alternative molecular therapeutic approach in spite of the current therapy of interferon-α and ribavirin against HCV which has limited efficiency. HCV structural gene E2 is mainly involved in viral cell entry via attachment with the host cell surface receptors i.e., CD81 tetraspanin, low density lipoprotein receptor (LDLR, scavenger receptor class B type 1 (SR-B1, and Claudin1 (CLDN1. Considering the importance of HCV E2 gene and cellular receptors in virus infection and silencing effects of RNAi, the current study was designed to target the cellular and viral factors as new therapeutic options in limiting HCV infection. Results In this study the potential of siRNAs to inhibit HCV-3a replication in serum-infected Huh-7 cells was investigated by combined treatment of siRNAs against the HCV E2 gene and HCV cellular receptors (CD81 and LDLR, which resulted in a significant decrease in HCV viral copy number. Conclusion From the current study it is concluded that the combined RNAi-mediated silencing of HCV E2 and HCV receptors is important for the development of effective siRNA-based therapeutic option against HCV-3a.

  3. 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.

  4. Acetaminophen-induced acute liver injury in HCV transgenic mice

    International Nuclear Information System (INIS)

    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.

  5. 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.

  6. Nucleic acid amplification technology screening for hepatitis C virus and human immunodeficiency virus for blood donations

    International Nuclear Information System (INIS)

    To investigate the performance of the commercial Roche COBAS AmpliScreen assay, and demonstrate whether the COBAS AmpliScreen human immunodeficiency virus-1 (HIV-1) test, v1.5, and COBAS AmpliScreen hepatitis C virus (HCV) v 2.0 for screening for HIV-1 and HCV RNA in the donated blood units from which plasma mini pools were collected, by nucleic acid amplification technology (NAT), could detect the positive pools and reduce the risk of transmission of infections for those routinely tested by serological assays. The study was performed on 3288 plasma samples collected from blood donors in a period of 13 months, from August 2004 to August 2005, at Al-Hada Armed Forces Hospital, Molecular Pathology Laboratory, Taif, Kingdom of Saudi Arabia. The samples were tested by the reverse transcriptase polymerase chain reaction (RT-PCR) after RNA extraction (this represents the major method in NAT assays), in parallel with the routine serological testing to detect qualitatively for HIV-1 and HCV. The NAT assays that include an automated COBAS AmpliPrep system for RNA extraction and COBAS Amplicor Analyzer using AmpliScreen kits for RT-PCR assays, and the routine serological screening assays for the detection of the HIV-1 and HCV RNA in the plasma samples from the blood donors have shown to be a reliable combination that would meet our requirements. The collected data further confirms the results from the serological assays and enables us to decrease the residual risk of transmission to a minimum with the finding of no seronegative window period donation. The results demonstrate that out of 3288 samples, the percentages of RT-PCR (NAT) negative blood donations that were also confirmed as seronegative were 99% for HCV, and 99.1% for HIV-1. The modified combined systems (automated COBAS AmpliPrep system for RNA extraction and COBAS Amplicor Analyzer using AmpliScreen kits for RT-PCR assays) for NAT screening assays has allowed the release of all blood donations supplied in the

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

    Science.gov (United States)

    Merkinaite, Simona; Lazarus, Jeffrey V; Gore, Charles

    2008-09-01

    The hepatitis C virus (HCV) is a major public health problem due to its high prevalence, high rate of onward transmission and health complications. As many as 85% of people infected with HCV may go on to become chronic carriers of the disease with the risk of developing liver cancer or cirrhosis. 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 data suggest that only between 10% and 40% of people with HCV in Europe are aware of their infection (up to 90% of the prevalent pool are undiagnosed in such countries as Germany or Poland). Though the virus affects people of all ages, races and backgrounds, in Europe, between 20% and 90% of new HCV cases have been identified among past or current injecting drug users (IDUs). It is of the utmost importance to improve both public awareness and access to early testing and counselling, with the goal of prevention of further infections, maintenance of health and provision of treatment to avoid cirrhosis and liver cancer. Additionally, as previous studies in central and eastern Europe show, evidence-based measures to prevent and manage HCV among IDUs, where most current transmission is concentrated, remain limited. Therefore, there is a strong need for intensified advocacy to put HCV higher on both public health and harm reduction agendas. PMID:18935772

  8. Co-infection rate of HIV, HBV and Syphilis among HCV seropositive identified blood donors in Kathmandu, Nepal

    OpenAIRE

    Shrestha, Ashish Chandra; Ghimire, Prakash; Tiwar, Bishnu Raj; Rajkarnikar, Manita

    2012-01-01

    Background: HIV, HBV, Syphilis and HCV share common modes of transmission. Objective: The study was aimed to determine the co-infection rate of HIV, HBV and Syphilis among HCV seropositive identified blood donors. Methods: The study was conducted on blood samples screened as HCV seropositive at Nepal Red Cross Society, Central Blood Transfusion Service, Kathmandu, Nepal. HCV seropositive samples were further tested for HIV, HBV and Syphilis. Results: Eight co-infections were observed in 139 H...

  9. HCV and HCC molecular epidemiology

    Directory of Open Access Journals (Sweden)

    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

  10. HCV counselling in haemophilia care.

    Science.gov (United States)

    Miller, R; Telfer, P

    1996-01-01

    The many areas of uncertainty about HCV make counselling patients with haemophilia and HCV a challenge. In this review a brief summary is made of the current understanding of the natural history of hepatitis C infection, the modes of transmission, diagnostic techniques, and treatment options available. This forms a necessary background to counselling patients and their contacts. Some difficulties are highlighted and counselling guidelines about the disease with patients are suggested. PMID:27213897

  11. Targeting HCV Entry For Development of Therapeutics

    Directory of Open Access Journals (Sweden)

    Jeffrey F. McKelvy

    2010-08-01

    Full Text Available Recent progress in defining the molecular mechanisms of Hepatitis C Virus (HCV entry affords the opportunity to exploit new viral and host targets for therapeutic intervention. Entry inhibitors would limit the expansion of the infected cell reservoir, and would complement the many replication inhibitors now under development. The current model for the pathway of entry involves the initial docking of the virus onto the cell surface through interactions of virion envelope and associated low density lipoproteins (LDL with cell surface glycosaminoglycans and lipoprotein receptors, followed by more specific utilization with other hepatocyte membrane proteins: Scavenger Receptor Class B type 1 (SR-BI, CD81, Claudin 1 (CLDN1 and Occludin (OCLN. The use of blockers of these interactions, e.g. specific antibodies, suggests that inhibition of any one step in the entry pathway can inhibit infection. Despite this knowledge base, the tools for compound screening, HCV pseudoparticles (HCVpp and cell culture virus (HCVcc, and the ability to adapt them to industrial use are only recently available and as a result drug discovery initiatives are in their infancy. Several therapies aiming at modulating the virus envelope to prevent host cell binding are in early clinical testing. The first test case for blocking a cellular co-receptor is an SR-BI modulator. ITX 5061, an orally active small molecule, targets SR-BI and has shown potent antiviral activity against HCVpp and HCVcc. ITX 5061 has exhibited good safety in previous clinical studies, and is being evaluated in the clinic in chronic HCV patients and patients undergoing liver transplantation. Entry inhibitors promise to be valuable players in the future development of curative therapy against HCV.

  12. High burden of HCV disease and poor access to HCV services among people who inject drugs in India: A cross-sectional study among 14,481 drug users across India

    Science.gov (United States)

    Solomon, Sunil Suhas; Mehta, Shruti H; Srikrishnan, Aylur K; Solomon, Suniti; McFall, Allison M.; Laeyendecker, Oliver; Celentano, David D; Iqbal, Syed H; Anand, Santhanam; Vasudevan, Canjeevaram K; Saravanan, Shanmugam; Lucas, Gregory M; Kumar, Muniratnam S; Sulkowski, Mark S; Quinn, Thomas C

    2014-01-01

    Background Globally, 90% of HCV-infected individuals reside in resource-limited settings (RLS). We characterized the prevalence of HCV, HIV/HCV co-infection, and the HCV care continuum among people who inject drugs (PWID) in India. Methods 14,481 PWID were sampled from 15 cities throughout India using respondent-driven sampling (RDS) from January–December 2013. HCV prevalence was estimated by the presence of anti-HCV antibodies incorporating RDS weights. HCV care continuum outcomes were self-reported except for viral clearance among treatment-experienced participants. Findings Median age was 30 years and 13,608/14,449 (92·4%) were male. Overall weighted HCV prevalence was 37·2% (5,777/14,447); HIV/HCV co-infection prevalence was 13·2% (2,085/14,435). Correlates of HCV infection included higher lifetime injection frequency, HIV positivity, and a higher prevalence of persons with HIV RNA > 1000 copies/ml in the community. Of 5,777 HCV antibody positive PWID, 440 (5·5%) were aware of their status, 225 (3·0%) had seen a doctor for their HCV, 79 (1·4%) had taken HCV treatment, and 18 (0·4%) had undetectable HCV RNA. Overall, 6,138/12,128 (50·5%) did not get tested for HCV because they had never heard of HCV. Among the 5,777 HCV antibody positives, 2,086 (34·4%) reported harmful/hazardous alcohol use of whom 1,082 (50·4%) were dependent; 3,007 (52.9%) reported recent needle sharing. Awareness of HCV positive status was significantly associated with higher education, HIV testing history, awareness of HIV positive status, and higher community antiretroviral therapy coverage. Interpretation The high burden of HCV and HIV/HCV co-infection coupled with low-access to HCV services highlights an urgent need to include RLS in the global HCV agenda. While newer treatments will become available globally in the near future, programs to improve awareness, and reduce disease progression and transmission need to be scaled-up without further delay. Failure to do so could

  13. Modeling HCV Disease in Animals: Virology, Immunology and Pathogenesis of HCV and GBV-B Infections

    Directory of Open Access Journals (Sweden)

    Cordelia eManickam

    2014-12-01

    Full Text Available Hepatitis C virus (HCV infection has become a global public health burden costing billions of dollars in health care annually. Even with rapidly advancing scientific technologies, this disease still looms large due to a lack of vaccines and affordable treatment options. The immune correlates of protection and predisposing factors towards chronicity remain major obstacles to development of HCV vaccines and immunotherapeutics due, at least in part, to lack of a tangible infection animal model. This review discusses the currently available animal models for HCV disease, with a primary focus on GB virus B (GBV-B infection of New World primates that recapitulates the dual hepacivirus phenotypes of acute viral clearance and chronic pathologic disease. HCV and GBV-B are also closely phylogenetically related, and advances in characterization of the immune systems of New World primates have already led to the use of this model for drug testing and vaccine trials. Herein, we discuss the benefits and caveats of the GBV-B infection model and discuss potential avenues for future development of novel vaccines and immunotherapies.

  14. Seroprevalences of HBV, HCV and HIV among healthcare workers in a state hospital

    OpenAIRE

    Tekin, Alicem; Deveci, Özcan

    2010-01-01

    Objectives: In present study was aimed to investigate the seroprevalences of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) among healthcare workers in Mardin Obstetric and Children Hospital between 2008 and 2009. Methods: In sera samples obtained from 180 healthcare workers, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), HCV antibody (anti-HCV) and HIV antibody (anti-HIV) markers were tested by chemiluminescent immun...

  15. Seroprevalences of HBV, HCV and HIV among healthcare workers in a state hospital

    OpenAIRE

    Özcan Deveci; Alicem Tekin

    2010-01-01

    Objectives: In present study was aimed to investigate the seroprevalences of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) among healthcare workers in Mardin Obstetric and Children Hospital between 2008 and 2009.Methods: In sera samples obtained from 180 healthcare workers, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), HCV antibody (anti-HCV) and HIV antibody (anti-HIV) markers were tested by chemiluminescent immunoassa...

  16. An accurate assay for HCV based on real-time fluorescence detection of isothermal RNA amplification.

    Science.gov (United States)

    Wu, Xuping; Wang, Jianfang; Song, Jinyun; Li, Jiayan; Yang, Yongfeng

    2016-09-01

    Hepatitis C virus (HCV) is one of the common reasons of liver fibrosis and hepatocellular carcinoma (HCC). Early, rapid and accurate HCV RNA detection is important to prevent and control liver disease. A simultaneous amplification and testing (SAT) assay, which is based on isothermal amplification of RNA and real-time fluorescence detection, was designed to optimize routine HCV RNA detection. In this study, HCV RNA and an internal control (IC) were amplified and analyzed simultaneously by SAT assay and detection of fluorescence using routine real-time PCR equipment. The assay detected as few as 10 copies of HCV RNA transcripts. We tested 705 serum samples with SAT, among which 96.4% (680/705) showed consistent results compared with routine real-time PCR. About 92% (23/25) discordant samples were confirmed to be same results as SAT-HCV by using a second real-time PCR. The sensitivity and specificity of SAT-HCV assay were 99.6% (461/463) and 100% (242/242), respectively. In conclusion, the SAT assay is an accurate test with a high specificity and sensitivity which may increase the detection rate of HCV. It is therefore a promising tool to diagnose HCV infection. PMID:27283884

  17. HCV NS3Ag: a reliable and clinically useful predictor of antiviral outcomes in genotype 1b hepatitis C virus-infected patients.

    Science.gov (United States)

    Ren, S; Jin, Y; Huang, Y; Ma, L; Liu, Y; Meng, C; Guan, S; Xie, L; Chen, X

    2016-07-01

    Since hepatitis C virus (HCV) non-structural 3 (NS3) protease inhibitor (PI) combined with pegylated interferon/ribavirin (PR) has been approved for chronic HCV genotype (GT) 1b infection, a reliable and clinically useful predictor combining with serum HCV RNA to predict early virologic response, breakthrough, and relapse is important during HCV antiviral treatment. We evaluated the role of HCV NS3 antigen (HCV NS3Ag) on the prediction of virologic response in patients with HCV GT1b during PR or PR/simeprevir (triple) therapy. Three hundred patients were recruited, and HCV RNA and HCV NS3Ag were tested at baseline and weeks 2, 4, 12, 24, 48, and 72. NS3Ag and HCV RNA were significantly related (r(2) = 0.67) in the whole patient selection. The kinetic pattern of HCV RNA and HCV NS3Ag during triple treatment was similar. HCV NS3Ag levels in the triple group closely followed those of HCV RNA; the r(2) values were 0.756 (baseline), 0.837 (2 weeks), 0.989 (4 weeks), and 0.993 (12 weeks), respectively. For patients treated with PR, the positive and negative predictive values (PPVs and NPVs) for viral response were 96.31 % and 67.19 %, respectively, at week 4 by using the decrease of NS3Ag (dHCV NS3Ag) combined with HCV RNA. At week 12, the PPV was similar at 94.16 %, while the NPV reached 87.26 %. The PPV and NPV for the prediction of relapse and breakthrough were 90.6 % and 76.7 %, respectively. HCV NS3Ag is a valuable marker and could be a supplementary predictor of HCV RNA for the prediction of antiviral response, breakthrough, or relapse during HCV antiviral treatment. PMID:27173787

  18. Prevalences and associated risk factors of HCV/HIV co-infection and HCV mono-infection among injecting drug users in a methadone maintenance treatment program in Taipei, Taiwan

    Directory of Open Access Journals (Sweden)

    Yen Yung-Feng

    2012-12-01

    Full Text Available Abstract Background Injecting drug users (IDUs in Taiwan contributed significantly to an HIV/AIDS epidemic in 2005. In addition, studies that identified risk factors of HCV/HIV co-infection among IDUs were sparse. This study aimed to identify risk factors of HCV/HIV co-infection and HCV mono-infection, as compared with seronegativity, among injecting drug users (IDUs at a large methadone maintenance treatment program (MMTP in Taipei, Taiwan. Methods Data from enrollment interviews and HCV and HIV testing completed by IDUs upon admission to the Taipei City Hospital MMTP from 2006–2010 were included in this cross-sectional analysis. HCV and HIV testing was repeated among re-enrollees whose HCV or HIV test results were negative at the preceding enrollment. Backward stepwise multinomial logistic regression was used to identify risk factors associated with HCV/HIV co-infection and HCV mono-infection. Results Of the 1,447 IDUs enrolled, the prevalences of HCV/HIV co-infection, HCV mono-infection, and HIV mono-infection were 13.1%, 78.0%, and 0.4%, respectively. In backward stepwise multinomial regression analysis, after controlling for potential confounders, syringe sharing in the 6 months before MMTP enrollment was significantly positively associated with HCV/HIV co-infection (adjusted odds ratio [AOR]=27.72, 95% confidence interval [CI] 13.30–57.76. Incarceration was also significantly positively associated with HCV/HIV co-infection (AOR=2.01, 95% CI 1.71–2.37 and HCV mono-infection (AOR=1.77, 95% CI 1.52–2.06, whereas smoking amphetamine in the 6 months before MMTP enrollment was significantly inversely associated with HCV/HIV co-infection (AOR=0.44, 95% CI 0.25–0.76 and HCV mono-infection (AOR=0.49, 95% CI 0.32–0.75. HCV seroincidence was 45.25/100 person-years at risk (PYAR; 95% CI 24.74–75.92/100 PYAR and HIV seroincidence was 0.53/100 PYAR (95% CI 0.06–1.91/100 PYAR among re-enrolled IDUs who were HCV- or HIV-negative at the

  19. 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

    OpenAIRE

    Latronico, Tiziana; Mascia, Claudia; Pati, Ilaria; Zuccala, Paola; Mengoni, Fabio; Marocco, Raffaella; Tieghi, Tiziana; Belvisi, Valeria; Lichtner, Miriam; Vullo, Vincenzo; Mastroianni, Claudio Maria; Liuzzi, Grazia Maria

    2016-01-01

    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 ...

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

    International Nuclear Information System (INIS)

    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)

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

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    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

  2. Animal models for HCV and HBV studies

    Directory of Open Access Journals (Sweden)

    Isabelle Chemin

    2007-02-01

    develop fulminant hepatitis, acute hepatitis, or chronic liver disease after adoptive transfer, and others spontaneously develop hepatocellular carcinoma (HCC. Among HCV transgenic mice, most develop no disease, but acute hepatitis has been observed in one model, and HCC in another. Although mice are not susceptible to HBV and HCV, their ability to replicate these viruses and to develop liver diseases characteristic of human infections provides opportunities to study pathogenesis and develop novel therapeutics In the search for the mechanism of hepatocarcinogenesis in hepatitis viral infection, two viral proteins, the core protein of hepatitis C virus (HCV and the HBx protein of hepatitis B virus (HBV, have been shown to possess oncogenic potential through transgenic mouse studies, indicating the direct involvement of the hepatitis viruses in hepatocarcinogenesis.

    This may explain the very high frequency of HCC in patients with HCV or HBV infection.

    Chimpanzees remain the only recognized animal model for the study of hepatitis C virus (HCV. Studies performed in chimpanzees played a critical role in the discovery of HCV and are continuing to play an essential role in defining the natural history of this important human pathogen. In the absence of a reproducible cell culture system, the infectivity titer of HCV challenge pools can be determined only in chimpanzees.

    Recent studies in chimpanzees have provided new insight into the nature of host immune responses-particularly the intrahepatic responses-following primary and secondary experimental HCV infections. The immunogenicity and efficacy of vaccine candidates against HCV can be tested only in chimpanzees. Finally, it would not have been possible to demonstrate

  3. HBV-DNA in hemodialysis patients infected by HCV

    International Nuclear Information System (INIS)

    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)

  4. HBV-DNA in hemodialysis patients infected by HCV

    Directory of Open Access Journals (Sweden)

    Arababadi Mohammad

    2009-01-01

    Full Text Available 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 de-termine 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 HBsAg. 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.

  5. ED-based screening programs for hepatitis C (HCV) highlight significant opportunity to identify patients, prevent downstream costs/complications.

    Science.gov (United States)

    2014-01-01

    New data suggest there is a huge opportunity for EDs to identify patients with the hepatitis C virus (HCV) and link them into care before downstream complications lead to higher medical costs and adverse outcomes. Early results from a pilot study at the University of Alabama Medical Center in Birmingham show that at least 12% of the targeted baby boomer population being screened for HCV in the ED is testing positive for HCV, with confirmatory tests showing that about 9% of the screened population is infected with the disease. Both the Centers for Disease Control in Atlanta and the US Preventive Services Task Force recommend one-time HCV screening for patients who were born between 1945 and 1965. Public health experts say 75% of HCV infections occur in patients born during the baby boomer years, and that roughly half of them are unaware of their HCV status. Researchers at UAB report that so many patients are testing positive for HCV that demand for care can quickly overwhelm the health system if new primary care/specialty resources are not identified. Administrators of ED-based HCV screening programs in both Birmingham and Houston note that EDs with existing screening programs for HIV should have the easiest time implementing HCV screening. They also stress that patients are more accepting of HCV screening, and that the counseling process is easier. PMID:24432549

  6. Increases in acute hepatitis C (HCV incidence across Europe: which regions and patient groups are affected?

    Directory of Open Access Journals (Sweden)

    Rockstroh J

    2012-11-01

    Full Text Available Background In the last decade, several outbreaks of sexually acquired acute HCV have been described in men who have sex with men (MSM infected with HIV in Australia, Europe, and North America. The aims of this study were to determine the incidence of acute HCV within the large EuroSIDA cohort and to explore possible regional differences throughout Europe and in different HIV transmission risk groups. Methods Baseline was defined as 1st Jan of 2002 or entry into EuroSIDA, whichever comes later. All patients from EuroSIDA who were HCV antibody-negative at baseline and had at least 2 HCV antibody test results available were included into the study. HCV seroconversion was defined as change from negative to positive HCV-antibody test within the observation period from 2002 onwards. Follow-up was counted from baseline to HCV antibody positivity for seroconverters and to the last HCV antibody-negative test result for those that did not seroconvert for HCV. Poisson regression analyses were performed to identify predictive factors for HCV seroconversion. Results A total of 150 HCV seroconversions (95 [63.3%] in MSM occurred in 4295 patients during 18,928 person years of follow-up (PYFU, overall incidence of 0.79 acute infections per 100 PYFU (95% CI: 0.67–0.92 (see figure. The incidence of HCV seroconversions increased from 0.47 (CI: 0.19–0.74 in 2002 to 2.34 (CI: 1.24–3.44 in 2010. Similar patterns were observed across all European regions (p=0.89, test for interaction. In multivariate analysis, IDU was associated with a higher incidence rate ratio (IRR than MSM: 4.59 (2.40–8.80; p<0.0001, South and East Europe both had higher IRR compared to Western Europe, respectively (1.98 [1.12–3.49]; p=0.018 and 2.41 [1.41–4.12]; p=0.0014. Calendar year per 2 years was also associated with a higher IRR (1.29 [1.19–1.39]; p<0.0001. Conclusion The incidence of acute HCV within EuroSIDA increased over time. Although, the incidence of seroconversion was

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

    International Nuclear Information System (INIS)

    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)

  8. 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

  9. Changing strategies for hepatitis C testing.

    Science.gov (United States)

    Teo, Chong Gee

    2012-01-01

    Recent approvals of direct-acting, orally delivered pharmaceuticals for the treatment of patients with infection by HCV and of a point-of-care assay for community screening of HCV infection have generated impetus to widen the identification of HCV-infected individuals. Diagnosis of HCV infection is, however, still based on the detection of anti-HCV immunoglobulin G. As treatment is intended for individuals with current infection, testing for evidence of infection would need to centre on the detection of HCV viraemia. Minimizing the complexity and costs associated with HCV nucleic acid testing and speeding the development and validation of HCV antigen assays expedite the identification of HCV-viraemic individuals. Establishing means to diagnose recent HCV infection and to engage in surveillance of drug-resistant HCV are also apposite. Successful implementation of these various measures brightens prospects for the eventual elimination of HCV. PMID:23322655

  10. Hepatitis C virus (HCV infection & risk factors for HCV positivity in injecting & non-injecting drug users attending a de-addiction centre in northern India

    Directory of Open Access Journals (Sweden)

    Debasish Basu

    2015-01-01

    Full Text Available Background & objectives: Injecting drug use is a major route of hepatitis C virus (HCV infection in India, but there may be other risk factors also. This study was carried out to determine the seroprevalence of anti-HCV antibody in injecting drug users (IDUs vs. non-IDUs (NIDUs, and to study the risk estimates for HCV seropositivity in the total sample of substance users with regard to various demographic, clinical, behavioural and personality factors. Methods: The IDUs (n = 201 and NIDUs (n = 219 were assessed for demographic, clinical and behavioural information, and were rated on instruments for severity of dependence, risk behaviour and personality profiles. Anti-HCV antibody was tested by ELISA and confirmed by recombinant immunoblot assay (RIBA test. Results: Almost one-third of the IDUs (64 of 201; 31.8% were positive for anti-HCV antibody, as opposed to only seven (3.2% of the NIDUs. The four risk factors strongly associated with HCV positivity in multivariate analysis were sharing syringe [Exp(B 75.04; 95%CI 18.28-307.96; P<0.001], reuse of injection accessories (16.39; 3.51-76.92; P<0.001, blood transfusion (5.88; 1.63-21.23; P=0.007 and IDU status (3.60; 1.26-10.31; P=0.017. Other variables less strongly but significantly associated with HCV positivity were multiple sex partners, opioid dependence, risk behaviour scores, impulsivity, and lower age of onset of drug use. Interpretation & conclusions: Our study showed a high seroprevalence of anti-HCV antibody in IDUs. In the substance users, HCV positivity was significantly and independently associated with several clinical, behavioural, and personality risk factors.

  11. Heterologous Immunity between Adenoviruses and Hepatitis C Virus: A New Paradigm in HCV Immunity and Vaccines.

    Science.gov (United States)

    Singh, Shakti; Vedi, Satish; Samrat, Subodh Kumar; Li, Wen; Kumar, Rakesh; Agrawal, Babita

    2016-01-01

    Adenoviruses (Ad) are commonly used as vectors for gene therapy and/or vaccine delivery. Recombinant Ad vectors are being tested as vaccines for many pathogens. We have made a surprising observation that peptides derived from various hepatitis C virus (HCV) antigens contain extensive regions of homology with multiple adenovirus proteins, and conclusively demonstrate that adenovirus vector can induce robust, heterologous cellular and humoral immune responses against multiple HCV antigens. Intriguingly, the induction of this cross-reactive immunity leads to significant reduction of viral loads in a recombinant vaccinia-HCV virus infected mouse model, supporting their role in antiviral immunity against HCV. Healthy human subjects with Ad-specific pre-existing immunity demonstrated cross-reactive cellular and humoral immune responses against multiple HCV antigens. These findings reveal the potential of a previously uncharacterized property of natural human adenovirus infection to dictate, modulate and/or alter the course of HCV infection upon exposure. This intrinsic property of adenovirus vectors to cross-prime HCV immunity can also be exploited to develop a prophylactic and/or therapeutic vaccine against HCV. PMID:26751211

  12. Heterologous Immunity between Adenoviruses and Hepatitis C Virus: A New Paradigm in HCV Immunity and Vaccines

    Science.gov (United States)

    Singh, Shakti; Vedi, Satish; Samrat, Subodh Kumar; Li, Wen; Kumar, Rakesh; Agrawal, Babita

    2016-01-01

    Adenoviruses (Ad) are commonly used as vectors for gene therapy and/or vaccine delivery. Recombinant Ad vectors are being tested as vaccines for many pathogens. We have made a surprising observation that peptides derived from various hepatitis C virus (HCV) antigens contain extensive regions of homology with multiple adenovirus proteins, and conclusively demonstrate that adenovirus vector can induce robust, heterologous cellular and humoral immune responses against multiple HCV antigens. Intriguingly, the induction of this cross-reactive immunity leads to significant reduction of viral loads in a recombinant vaccinia-HCV virus infected mouse model, supporting their role in antiviral immunity against HCV. Healthy human subjects with Ad-specific pre-existing immunity demonstrated cross-reactive cellular and humoral immune responses against multiple HCV antigens. These findings reveal the potential of a previously uncharacterized property of natural human adenovirus infection to dictate, modulate and/or alter the course of HCV infection upon exposure. This intrinsic property of adenovirus vectors to cross-prime HCV immunity can also be exploited to develop a prophylactic and/or therapeutic vaccine against HCV. PMID:26751211

  13. 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.

  14. A Nucleotide Binding Motif in Hepatitis C Virus (HCV) NS4B Mediates HCV RNA Replication

    OpenAIRE

    Einav, Shirit; Elazar, Menashe; Danieli, Tsafi; Glenn, Jeffrey S.

    2004-01-01

    Hepatitis C virus (HCV) is a major cause of viral hepatitis. There is no effective therapy for most patients. We have identified a nucleotide binding motif (NBM) in one of the virus's nonstructural proteins, NS4B. This structural motif binds and hydrolyzes GTP and is conserved across HCV isolates. Genetically disrupting the NBM impairs GTP binding and hydrolysis and dramatically inhibits HCV RNA replication. These results have exciting implications for the HCV life cycle and novel antiviral s...

  15. A Nucleotide Binding Motif in Hepatitis C Virus (HCV) NS4B Mediates HCV RNA Replication

    Science.gov (United States)

    Einav, Shirit; Elazar, Menashe; Danieli, Tsafi; Glenn, Jeffrey S.

    2004-01-01

    Hepatitis C virus (HCV) is a major cause of viral hepatitis. There is no effective therapy for most patients. We have identified a nucleotide binding motif (NBM) in one of the virus's nonstructural proteins, NS4B. This structural motif binds and hydrolyzes GTP and is conserved across HCV isolates. Genetically disrupting the NBM impairs GTP binding and hydrolysis and dramatically inhibits HCV RNA replication. These results have exciting implications for the HCV life cycle and novel antiviral strategies. PMID:15452248

  16. Gene profiling, biomarkers and pathways characterizing HCV-related hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Buonaguro Luigi

    2009-10-01

    Full Text Available Abstract Background Hepatitis C virus (HCV infection is a major cause of hepatocellular carcinoma (HCC worldwide. The molecular mechanisms of HCV-induced hepatocarcinogenesis are not yet fully elucidated. Besides indirect effects as tissue inflammation and regeneration, a more direct oncogenic activity of HCV can be postulated leading to an altered expression of cellular genes by early HCV viral proteins. In the present study, a comparison of gene expression patterns has been performed by microarray analysis on liver biopsies from HCV-positive HCC patients and HCV-negative controls. Methods Gene expression profiling of liver tissues has been performed using a high-density microarray containing 36'000 oligos, representing 90% of the human genes. Samples were obtained from 14 patients affected by HCV-related HCC and 7 HCV-negative non-liver-cancer patients, enrolled at INT in Naples. Transcriptional profiles identified in liver biopsies from HCC nodules and paired non-adjacent non-HCC liver tissue of the same HCV-positive patients were compared to those from HCV-negative controls by the Cluster program. The pathway analysis was performed using the BRB-Array- Tools based on the "Ingenuity System Database". Significance threshold of t-test was set at 0.001. Results Significant differences were found between the expression patterns of several genes falling into different metabolic and inflammation/immunity pathways in HCV-related HCC tissues as well as the non-HCC counterpart compared to normal liver tissues. Only few genes were found differentially expressed between HCV-related HCC tissues and paired non-HCC counterpart. Conclusion In this study, informative data on the global gene expression pattern of HCV-related HCC and non-HCC counterpart, as well as on their difference with the one observed in normal liver tissues have been obtained. These results may lead to the identification of specific biomarkers relevant to develop tools for detection

  17. Co-infection rate of HIV, HBV and Syphilis among HCV seropositive identified blood donors in Kathmandu, Nepal

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    Ashish Chandra Shrestha

    2012-02-01

    Full Text Available Background: HIV, HBV, Syphilis and HCV share common modes of transmission. Objective: The study was aimed to determine the co-infection rate of HIV, HBV and Syphilis among HCV seropositive identified blood donors. Methods: The study was conducted on blood samples screened as HCV seropositive at Nepal Red Cross Society, Central Blood Transfusion Service, Kathmandu, Nepal. HCV seropositive samples were further tested for HIV, HBV and Syphilis. Results: Eight co-infections were observed in 139 HCV seropositives with total co-infection rate of 5.75% (95% CI = 2.52-11.03. Conclusion: Co-infection of HIV, HBV and Syphilis with HCV is prevalent in the healthy looking blood donors of Kathmandu, Nepal.

  18. Transfusionsoverført hepatitis C. Den danske "lookback"-undersøgelse. Den Danske HCV lookback gruppe

    DEFF Research Database (Denmark)

    Christensen, P B; Grønbaek, K E; Krarup, H B

    2000-01-01

    This study accumulated results of the HCV lookback in Denmark and described the morbidity of the infected recipients. Donor records were identified for at least ten years back, and recipients still alive were tested for hepatitis C. Those with positive results were referred for clinical evaluation....... A total of 150 Danish anti-HCV positive donors had donated blood to 1018 recipients of whom 288 (29%) were still alive. Because of age, malignancy or other severe diseases 118 (41%) of these were not contacted. Of 157 recipients screened for HCV, 128 (82%) were anti-HCV positive and 88 (56%) were...

  19. The epidemiologic feature of HCV prevalence in Fujian

    Institute of Scientific and Technical Information of China (English)

    Ling Fen Li; Yong Zhou; Sheng Xia; Li Lai Zhao; Zi Xin Wang; Cheng Qin Wang

    2000-01-01

    AIM To investigate the epidemiological features of HCV prevalence, a seroepidemiological survey on HCVinfection has been carried out in Fujian since 1992.METHODS Using stratified multistage random cluster sampling, 3809 serum samples collected from 1237families in the diseases surveillance points were tested by UBI HCV EIA kit.RESULTS The results showed that the prevalence rate was 3.99%. The rate in male and female was3.63% and 4.25%, and in urban and rural 3.12% and 4.6% respectively (P>0.05). There was lower ratein children aged under 10 years. The highest rate was in 20 - 24 years old. The rates in different areas wereranged from 1.39% to 6.08% (P<0.05). The intrafamilial transmission was not important, indicating nointrafamilial aggregation. The superinfection of HCV with HAV, HBV and HEV were existed. The HCVinfection was slightly correlated with the history of hepatitis and transfusion.CONCLUSION It suggests that the HCV transmission among the population in Fujian is mainly sporadicinfection.

  20. Prevalence and Risk Factors of Hepatitis C Infection (HCV in Birjand, Iran, 2014

    Directory of Open Access Journals (Sweden)

    Ebrahimzadeh

    2016-01-01

    Full Text Available Background Hepatitis C virus (HCV infection is an important global concern, with a frequency of 3% (i.e., 170 million of the population has HCV-Ab. Additionally, 50% of HCV and 80% of transfusion transmitted infections (TTI are chronic. In 20% of cases, HCV occurs as an acute infection, and in the remaining 80% of cases, it becomes chronic. In chronic patients, risk of cirrhosis is up to 44%, risk of hepatocellular carcinoma (HCC is 13%, and risk of mortality is 14%. As there is no vaccine available for the virus yet, and since most of the cases are asymptomatic, attention to the epidemiology of the disease among the population is a pressing concern. Objectives The aim of this study is to determine the prevalence and risk factors of HCV in Birjand city. Patients and Methods In this descriptive-analytical study, 5,235 people who live in Birjand city were selected; after gaining permission for the study, a signed consent form was obtained from each patient. Prevalence of HCV was determined by ELISA test, and positive cases underwent Polymerase chain reaction (PCR and genotyping for confirmation. Results The mean age of the participants was 39.7 ± 14.4. Among them, 52.2% were female and 29.9% had university degrees. Prevalence of HCV-Ab+ was about 0.2% with ELISA, and 0.14% of entire group were confirmed by PCR. No significant relationship was found for age, sex, and education (P > 0.05. Also, there was no significant relationship found with risk factors such as endoscopy, blood transfusion, surgery, hospitalization, phlebotomy, and alcohol drinking (P > 0.05. HCV-Ab was 200 times more prevalent in IV-drug abusers compared to non-addicted people. Also, the prevalence of HCV-Ab in non-IV-drug abuser addicts was 9.3 times higher than in non-addict patients. Prevalence of HCV-Ab in patients who reported illicit sexual activities was 13.3 times higher. In patients with a familial history of HCV, infection was 26.3 times more prevalent than in patients

  1. Inhibition of HCV 3a core gene through Silymarin and its fractions

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    Nawaz Zafar

    2011-04-01

    Full Text Available Abstract Hepatitis C is a major health problem affecting 270 million individuals in world including Pakistan. Current treatment regimen, interferon alpha and ribavirin only cure half of patients due to side effects and high cost. Results In the present study Silybum marianum (Milk thistle seeds were collected, extracted and analyzed against HCV 3a core gene by transiently transfecting the liver cells with HCV core plasmid. Our results demonstrated that Silymarin (SM dose dependently inhibit the expression or function of HCV core gene at a non toxic concentration while the GAPDH remained constant. To identify the active ingredient, SM was fractioned by thin layer chromatography (TLC, column chromatography and HPLC. Purified fractions were tested for HCV core gene and western blotting results showed that two factions of SM (S1 and S2 inhibit HCV 3a core expression or function in liver cells Conclusion Our results suggest SM and its fractions (S1 and S2 inhibit HCV core gene of 3a genotype and combination of SM and its fractions with interferon will be a better option to treat HCV infection

  2. 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)

    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)

  3. Toward a simple risk assessment screening tool for HCV infection in Egypt.

    Science.gov (United States)

    El-Ghitany, Engy M; Farghaly, Azza G; Abdel Wahab, Moataza M; Farag, Shehata; Abd El-Wahab, Ekram W

    2016-10-01

    Asymptomatic patients with HCV infection identified through screening program could benefit not only from treatment but also from other interventions such as counseling to maintain health and avoid risk behaviors. This might prevent the spread of infection and result in significant public health benefits. However, mass screening would quickly deplete resources. This work aims to develop a brief HCV risk assessment questionnaire that inquires initially about a wide range of risk factors found to be potentially associated with HCV infection in order to identify the few most significant questions that could be quickly used to facilitate cost-effective HCV case-finding in the general population in Egypt. An exhaustive literature search was done to include all reported HCV risk factors that were pooled in a 65 item questionnaire. After an initial pilot study, a case-control study was performed that included 1,024 cases and 1,046 controls. In a multivariable model, a list of independent risk factors were found to be significant predictors for being HCV seropositive among two age strata (45 years) for each gender. A simplified model that assigned values of the odds ratio as a weight for each factor present predicted HCV infection with high diagnostic accuracy. Attaining the defined cut-off value of the total risk score enhances the effectiveness of screening. HCV risk factors in the Egyptian population vary by age and gender. An accurate prediction screening tool can be used to identify those at high risk who may benefit most from HCV serologic testing. These results are to be further validated in a large scale cross-sectional study to assess the wider use of this tool. J. Med. Virol. 88:1767-1775, 2016. © 2016 Wiley Periodicals, Inc. PMID:26970264

  4. Heterologous Immunity between Adenoviruses and Hepatitis C Virus: A New Paradigm in HCV Immunity and Vaccines

    OpenAIRE

    Singh, Shakti; Vedi, Satish; Samrat, Subodh Kumar; Li, Wen; Kumar, Rakesh; Agrawal, Babita

    2016-01-01

    Adenoviruses (Ad) are commonly used as vectors for gene therapy and/or vaccine delivery. Recombinant Ad vectors are being tested as vaccines for many pathogens. We have made a surprising observation that peptides derived from various hepatitis C virus (HCV) antigens contain extensive regions of homology with multiple adenovirus proteins, and conclusively demonstrate that adenovirus vector can induce robust, heterologous cellular and humoral immune responses against multiple HCV antigens. Intr...

  5. Comparison of seropositivity of HCV between oral lichen planus and healthy control group in Hamedan province (west of Iran

    Directory of Open Access Journals (Sweden)

    Ahmad Reza Mobaien

    2011-10-01

    Full Text Available Background: Lichen planus is an idiopathic inflammatory disease of the skin, nail, hair and mucous membranes. Oral lichen planus (LP is a chronic inflammatory condition that affects the oral mucous membranes with a variety of clinical presentations. Various etiologies include HCV suggested for LP, and the aim of this study was comparison of seropositivity of HCV in LP patients and control group. Methods: All oral LP patients that were referred to dermatology clinic of farshchian hospitalwere entered in the study. Five cc of clot blood was taken from each patient and tested for anti-HCVand when anti-HCV tested positive another 2cc clot bloodwas taken for HCV-Rt-PCR test. The results were analyzed with SPSS 16. Results: This prospective cross-sectional study was conducted on 30 oral lichen planus patients [males 13(43.3% females 17(56.7%] with mean ages of 46±13.7years and 60 healthy individual [males 26(43.3% females 34(56.7%]. There was no oral lichen planus patients who had anti-HCV positive whiles 2 males(3.3% of healthy group had anti-HCV positive which was confirmed by HCV-Rt-PCR. Conclusions: This study showed that there is no correlation between seropositivity of HCV and oral lichen planus in our patients in the west of Iran.

  6. HCV genotyping using statistical classification approach

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    Norris Ellie D

    2009-07-01

    Full Text Available Abstract The genotype of Hepatitis C Virus (HCV strains is an important determinant of the severity and aggressiveness of liver infection as well as patient response to antiviral therapy. Fast and accurate determination of viral genotype could provide direction in the clinical management of patients with chronic HCV infections. Using publicly available HCV nucleotide sequences, we built a global Position Weight Matrix (PWM for the HCV genome. Based on the PWM, a set of genotype specific nucleotide sequence "signatures" were selected from the 5' NCR, CORE, E1, and NS5B regions of the HCV genome. We evaluated the predictive power of these signatures for predicting the most common HCV genotypes and subtypes. We observed that nucleotide sequence signatures selected from NS5B and E1 regions generally demonstrated stronger discriminant power in differentiating major HCV genotypes and subtypes than that from 5' NCR and CORE regions. Two discriminant methods were used to build predictive models. Through 10 fold cross validation, over 99% prediction accuracy was achieved using both support vector machine (SVM and random forest based classification methods in a dataset of 1134 sequences for NS5B and 947 sequences for E1. Prediction accuracy for each genotype is also reported.

  7. HCV genotype distribution and possible transmission risks in Lahore, Pakistan

    Institute of Scientific and Technical Information of China (English)

    Waqar; Ahmad; Bushra; Ijaz; Fouzia; Tahir; Javed; Shah; Jahan; Imran; Shahid; Fawad; Mumtaz; Khan; Sajida; Hassan

    2010-01-01

    AIM: To investigate the prevalence of hepatitis C virus (HCV) genotypes and their association with possible transmission routes in the general population of Lahore, as the data exclusively related to this city is limited. METHODS: Complete data regarding patient's history, possible route of infection and biochemical tests was collected from the public hospital for 1364 patients. SPSS version 16 windows software was used for data analysis by univariate and multivariate techniques. RESULTS: Age range ≤ 40 yea...

  8. No requirement of HCV 5'NCR for HCV-like particles assembly in insect cells

    Institute of Scientific and Technical Information of China (English)

    Wei Zhao; Guo-Yang Liao; Yah-Jun Jiang; Shu-De Jiang

    2003-01-01

    AIM: To express all three HCV structural proteins in the presence or absence of HCV 5'NCR to investigate the requirement of 5'NCR for the assembly of HCV-like particles in insect cells.METHODS: HCV structural protein encoding sequences CE1E2 and 5'NCR-CE1E2 were amplified with PCR.Recombinant baculovirus were constructed with recombinant DNA techniques. HCV structural proteins expressed in insect cells were analyzed by immunofluorescence and SDS-PAGE.Immunoprecipitation experiment of insect cell lysates with anti-E2 monodonal antibody (Mab) was carried out and the immunoprecipitated proteins were subjected to SDS-PAGE and immunoblotting with anti-C, anti-E2 Mabs and HCV positive serum. The virus-like particles in insect cells were visualized by electron microscopy (EM). The HCV-like particles were purified by sucrose gradient centrifugation and identified by EM and immune aggregation EM.RESULTS: The recombinant baculovirus reBV/CE1E2containing HCV C, E1, E2 genes and reBV/CS containing the same structural protein genes plus 5'NCR were constructed. The insect cells infected with either reBV/CE1E2or reBV/CS expressed HCV C, E1 and E2 proteins with a molecular weight of 20 kD, 35 kD and 66 kD respectively.The results of immunoprecipitation and the immunoblotting revealed the coimmunoprecipitation of C, E1, and E2proteins, indicating the interaction of HCV structural proteins expressed in insect cells. Electron microscopy of insect cells infected with reBV/CE1E2 or reBV/CS demonstrated spherical particles (40 to 60 nm in diameter)similar to the HCV virions from sera or hepatic tissues of HCV infected humans. The HCV-like particles were partially purified by sucrose gradient centrifugation, and the purified VLPs showed immuno-reactivity with anti-HCV antibodies.CONCLUSION: HCV 5'NCR is not required for the assembly of HCV-like particles in insect cells, HCV core and envelope proteins are sufficient for viral particle formation.

  9. Multicentric performance analysis of HCV quantification assays and its potential relevance for HCV treatment.

    Science.gov (United States)

    Wiesmann, F; Naeth, G; Berger, A; Hirsch, H H; Regenass, S; Ross, R S; Sarrazin, C; Wedemeyer, H; Knechten, H; Braun, P

    2016-06-01

    An accurate quantification of low viremic HCV RNA plasma samples has gained importance since the approval of direct acting antivirals and since only one single measurement predicts the necessity of a prolonged or shortened therapy. As reported previously, HCV quantification assays such as Abbott RealTime HCV and Roche COBAS AmpliPrep/COBAS TaqMan HCV version 2 (CTM v2) may vary in sensitivity and precision particularly in low-level viremia. Importantly, substantial variations were previously demonstrated between some of these assays compared to the Roche High Pure System/COBAS TaqMan assay (HPS) reference assay, which was used to establish the clinical decision points in clinical studies. In this study, the reproducibility of assay performances across several laboratories was assessed by analysing quantification results generated by six independent laboratories (3× RealTime, 3× CTM v2) in comparison with one HPS reference laboratory. The 4th WHO Standard was diluted to 100, 25 and 10 IU/ml, and aliquots were tested in triplicates in 5 independent runs by each assay in the different laboratories to assess assay precision and detection rates. In a second approach, 2 clinical samples (GT 1a & GT 1b) were diluted to 100 and 25 IU/ml and tested as described above. While the result range for WHO 100 IU/ml replicates across all laboratories was similar in this analysis, the CVs of each laboratory ranged from 19.3 to 25.6 % for RealTime laboratories and were lower than CVs of CTM v2 laboratories with a range of 26.1-47.3 %, respectively, and also in comparison with the CV of the HPS reference laboratory (34.9 %). At WHO standard dilution of 25 IU/ml, 24 replicates were quantified by RealTime compared to 8 replicates with CTM v2. Results of clinical samples again revealed a higher variation of CTM v2 results as compared to RealTime values. (CVs at 100 IU/ml: RealTime: 13.1-21.0 % and CTM v2: 15.0-32.3 %; CVs at 25 IU/ml: RealTime 17.6-34.9 % and CTM v2 28

  10. High HCV seroprevalence and HIV drug use risk behaviors among injection drug users in Pakistan

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    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.

  11. 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 effici...

  12. Il controllo di qualità nell’impiego della PCR applicata alla determinazione qualitativa dell’HCV-RNA

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    Giuseppe Giuliani

    2004-03-01

    Full Text Available Detection of hepatitis C virus (HCV RNA in samples of plasma/serum has become an essential part of the diagnosis and management of HCV-infected patients. Qualitative HCV-RNA tests are used to identify acute HCV infections as well as chronic HCV carriers.In recent years,a variety of commercial and non commercial test systems have been developed for this purpose. Each of these methods is calibrate with proprietary standards and exhibits its own sensitivity (detection limit and specificity. Obviously, laboratories performing HCV-RNA test should report accurate and reliable results regardless of the type of assay used.Where commercial kit are used for part of or the complete analytical procedure, documented validation points already covered by the kit manufacturer can substitute for the validation by the user.Nevertheless, the performance of the kit with respect to its intended use has to be demonstrated by the user. One of the best ways to assess the performance of individual laboratories for validation of qualitative HCV-RNA test is determine: 1. Specificity. In order to validate the specificity of the analytical procedure, at least 100 HCV-RNA-negative plasma pools should be tested and shown to be non-reactive. 2. Positive cut-off point (detection limit/sensitivity.The positive cut-off point (as defined in the Ph Eur General Method 2. 6. 21 is the minimum number of the target sequences per volume sample which can be detected in 95% of test runs.A dilution series of a working reagent or reference material, which has been calibrated against the WHO HCV International Standard (96/790, should be tested on different days to examine variation between test runs.At least 3 independent dilution series should be tested with a sufficient number of replicates at each dilution to give a total number of 24 test results for each dilution to enable a statistical analysis of the results; 3. Robustness.To demonstrate robustness, at least 20 HCV-RNA negative plasma

  13. The Molecular Epidemiological Study of HCV Subtypes among Intravenous Drug Users and Non-Injection Drug Users in China.

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    Jun Tao

    Full Text Available More than half of intravenous drug users (IDUs in China suffer from the Hepatitis C virus (HCV. The virus is also more prevalent in non-injection drug users (NIDUs than in the general population. However, not much is known about HCV subtype distribution in these populations.Our research team conducted a cross-sectional study in four provinces in China. We sampled 825 IDUs and 244 NIDUs (1162 total, genotyped each DU's virus, and performed a phylogenetic analysis to differentiate HCV subtypes.Nucleic acid testing (NAT determined that 82% percent (952/1162 of samples were HCV positive; we subtyped 90% (859/952 of these. We found multiple HCV subtypes: 3b (249, 29.0%, 3a (225, 26.2%, 6a (156, 18.2%, 1b (137, 15.9%, 6n (50, 5.9%, 1a (27, 3.1%, and 2a (15, 1.7%. An analysis of subtype distributions adjusted for province found statistically significant differences between HCV subtypes in IDUs and NIDUs.HCV subtypes 3b, 3a, 6a, and 1b were the most common in our study, together accounting for 89% of infections. The subtype distribution differences we found between IDUs and NIDUs suggested that sharing syringes was not the most likely pathway for HCV transmission in NIDUs. However, further studies are needed to elucidate how NIDUs were infected.

  14. Association of HCV Core Antigen Seropositivity with Long-Term Mortality in Patients on Regular Hemodialysis

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    Akihiko Kato

    2012-03-01

    Full Text Available Anti-hepatitis C virus (HCV antibody seropositivity is independently associated with poor prognosis in hemodialysis (HD patients. However, anti-HCV antibody cannot distinguish between patients with active infection and those who have recovered from infection. We therefore aimed in this study to examine the association of HCV core antigen (HCVcAg seropositivity with mortality in HD patients. We first measured serum HCVcAg using an immunoradiometric assay and anti-HCV antibody in 405 patients on regular HD, and followed them for 104 months. There were 82 patients (20.2% who had been positive for anti-HCV antibodies; 57 (69.5% of these were positive for HCVcAg. During the follow-up, 29 patients were excluded, so we tested the association of HCVcAg seropositivity with all-cause, cardiovascular (CV and non-CV mortalities in 376 patients. A total of 209 patients (55.6% had expired during the observational period, 92 out of them due to CV causes. After adjusting for comorbid parameters, HCVcAg was independently associated with overall mortality (HR 1.61, 95% CI 1.05–2.47, p < 0.05. HCV infection was significantly related to liver disease-related mortality. Past HCV infection also contributed to CV mortality (HR 2.63, 95% CI 1.27–5.45, p < 0.01. In contrast, anti-HCV antibody and HCVcAg seropositivities did not associate with infectious disease-related and cancer-related (expect for hepatocellular carcinoma mortality. It follows from these findings that HCVcAg serology is associated with all-cause and CV mortality in HD patients.

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

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    Mohamed A Daw

    Full Text Available 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.

  16. Upregulated hepatic expression of mitochondrial PEPCK triggers initial gluconeogenic reactions in the HCV-3 patients

    Institute of Scientific and Technical Information of China (English)

    Taimoor; Islam; Sheikh; Tashfeen; Adam; Ishtiaq; Qadri

    2015-01-01

    Objective: To identify the differential expression of candidate gluconeogenic genes which may initiate hepatitis C virus(HCV) related metabolic disorder during early stages of disease. Methods: Patients of diverse age and sex, with positive HCV genotype 3(HCV-3) RNA in serum and with no history of other related infections, co-infections, alcoholism, diabetes or chemotherapeutic treatments were considered for this study. Semi-quantitative reverse transcriptase PCR analysis and quantitative fold change analysis of the fresh liver biopsies of eight chronically infected HCV-3 patients and six healthy individuals were evaluated for three potential biomarkers involved in glucose homeostasis induction, namely mitochondrial phosphoenolpyruvate carboxykinase 2(PCK2), glucose-6-phosphatase catalytic subunit(G6PC) and associated forkhead box protein 01(FOXO1). Results: Symptomatic evaluation, clinical history and blood test were conducted according to general disease prognosis procedures and reported here. Significantly upregulated expression of PCK2 independent of age, sex and viral infectivity levels in all HCV patients was observed, whereas no significant changes in the expression of G6 PC and FOXO1 were found. Conclusions: PCK2 triggers initial gluconeogenic reactions which ultimately result in the accumulation of glycogen in the liver hepatocytes. We therefore suggest that the overproduction of PCK2 has important physiological role in the onset of metabolic disorder in the HCV-3 patients.

  17. Upregulated hepatic expression of mitochondrial PEPCK triggers initial gluconeogenic reactions in the HCV-3 patients

    Institute of Scientific and Technical Information of China (English)

    Taimoor Islam Sheikh; Tashfeen Adam; Ishtiaq Qadri

    2015-01-01

    Objective:To identify the differential expression of candidate gluconeogenic genes which may initiate hepatitis C virus (HCV) related metabolic disorder during early stages of disease. Methods:Patients of diverse age and sex, with positive HCV genotype 3 (HCV-3) RNA in serum and with no history of other related infections, co-infections, alcoholism, diabetes or chemotherapeutic treatments were considered for this study. Semi-quantitative reverse transcriptase PCR analysis and quantitative fold change analysis of the fresh liver biopsies of eight chronically infected HCV-3 patients and six healthy individuals were evaluated for three potential biomarkers involved in glucose homeostasis induction, namely mitochondrial phosphoenolpyruvate carboxykinase 2 (PCK2), glucose-6-phosphatase catalytic subunit (G6PC) and associated forkhead box protein 01 (FOXO1).Results:Symptomatic evaluation, clinical history and blood test were conducted according to general disease prognosis procedures and reported here. Significantly upregulated expression ofPCK2 independent of age, sex and viral infectivity levels in all HCV patients was observed, whereas no significant changes in the expression ofG6PC andFOXO1were found.Conclusions:PCK2 triggers initial gluconeogenic reactions which ultimately result in the accumulation of glycogen in the liver hepatocytes. We therefore suggest that the overproduction of PCK2 has important physiological role in the onset of metabolic disorder in the HCV-3 patients.

  18. 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. PMID:23192857

  19. 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.

  20. 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.

  1. 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.

    Science.gov (United States)

    Latronico, Tiziana; Mascia, Claudia; Pati, Ilaria; Zuccala, Paola; Mengoni, Fabio; Marocco, Raffaella; Tieghi, Tiziana; Belvisi, Valeria; Lichtner, Miriam; Vullo, Vincenzo; Mastroianni, Claudio Maria; Liuzzi, Grazia Maria

    2016-01-01

    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. PMID:27023536

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

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    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.

  3. New Insights in Recurrent HCV Infection after Liver Transplantation

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    Shih-Hsien Hsu

    2013-01-01

    Full Text Available Hepatitis C virus (HCV is a small-enveloped RNA virus belonging to the Flaviviridae family. Since first identified in 1989, HCV has been estimated to infect 170 million people worldwide. Mostly chronic hepatitis C virus has a uniform natural history, from liver cirrhosis to the development of hepatocellular carcinoma. The current therapy for HCV infection consists of a combination of Pegylated interferon and ribavirin. On the other hand, HCV-related liver disease is also the leading indication for liver transplantation. However, posttransplant HCV re-infection of the graft has been reported to be universal. Furthermore, the graft after HCV re-infection often results in accelerated progression to liver failure. In addition, treatment of recurrent HCV infection after liver transplantation is often compromised by enhanced adverse effects and limited efficacy of interferon-based therapies. Taken together, poor outcome after HCV re-infection, regardless of grafts or recipients, poses a major issue for the hepatologists and transplant surgeons. The aim of this paper is to review several specific aspects regarding HCV re-infection after transplant: risk factors, current therapeutics for HCV in different stages of liver transplantation, cellular function of HCV proteins, and molecular mechanisms of HCV entry. Hopefully, this paper will inspire new strategies and novel inhibitors against recurrent HCV infection after liver transplantation and greatly improve its overall outcome.

  4. 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.

  5. HIV and HCV prevalence and incarceration-related risks among injecting drug users in three West Bank governorates.

    Science.gov (United States)

    Štulhofer, Aleksandar; Jwehan, Isam; AbuRabie, Randa

    2016-09-01

    In the Middle East, the HIV epidemic among injecting drug users (IDUs) seems to be in an early phase, which increases the importance of prevention and systematic risk surveillance. To gain information about HIV and HCV infection rates among IDUs in the West Bank, a biobehavioral survey was conducted using time-location sampling in the Ramallah, Hebron, and Bethlehem governorates in 2013. The researchers recruited 288 Palestinian IDUs ages 16-64 (Mage = 39.2, SD = 11.11). While no HIV cases were found in the sample, 41% of participants tested positive for HCV. Imprisonment was common among participants (83%), so we explored the association of incarceration experience with HCV infection and HIV testing. In multivariate assessments, incarceration was shown to increase the odds of being infected with HCV and ever tested for HIV. HIV prevention should be strengthened in West Bank prisons and correctional facilities, and imprisonment for drug use re-examined. PMID:26936370

  6. Down-regulation of IRES containing 5'UTR of HCV genotype 3a using siRNAs

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    Ali Ashfaq Usman

    2011-05-01

    Full Text Available Abstract Background Hepatitis C virus (HCV is a major causative agent of liver associated diseases leading to the development of hepatocellular carcinoma (HCC all over the world and genotype-3a responsible for most of the cases in Pakistan. Due to the limited efficiency of current chemotherapy of interferon-α (IFN-α and ribavirin against HCV infection alternative options are desperately needed out of which the recently discovered RNAi represent a powerful silencing approach for molecular therapeutics through a sequence-specific RNA degradation process to silence virus infection or replication. HCV translation is mediated by a highly conserved internal ribosome entry site (IRES within the 5'UTR region making it a relevant target for new drug development. Materials and methods The present study was proposed to assess and explore the possibility of HCV silencing using siRNA targeting 5'UTR. For this analysis full length HCV 5'UTR of HCV-3a (pCR3.1/5'UTR was tagged with GFP protein for in vitro analysis in Huh-7 cells. siRNA targeting 5'UTR were designed, and tested against constructed vector in Huh-7 cell line both at RNA and Protein levels. Furthermore, the effect of these siRNAs was confirmed in HCV-3a serum infected Huh-7 cell line. Results The expression of 5'UTR-GFP was dramatically reduced both at mRNA and protein levels as compared with Mock transfected and control siRNAs treated cells using siRNAs against IRES of HCV-3a genotype. The potential of siRNAs specificity to inhibit HCV-3a replication in serum-infected Huh-7 cells was also investigated; upon treatment with siRNAs a significant decrease in HCV viral copy number and protein expression was observed. Conclusions Overall, the present work of siRNAs against HCV 5'UTR inhibits HCV-3a expression and represents effective future therapeutic opportunities against HCV-3a genotype.

  7. 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.

  8. Ever closer to a prophylactic vaccine for HCV

    OpenAIRE

    Swadling, Leo; Klenerman, Paul; Barnes, Eleanor

    2013-01-01

    Introduction With 3 – 4 million new infections occurring annually, hepatitis C virus (HCV) is a major global health problem. There is increasing evidence to suggest that HCV will be highly amenable to a vaccine approach, and despite advances in treatment, a vaccine remains the most cost-effective and realistic means to significantly reduce the worldwide mortality and morbidity associated with persistent HCV infection. Areas covered In this review we discuss immune responses to HCV during natu...

  9. Nicht-invasive Fibrosegradbestimmung bei Patienten mit HIV-Monoinfektion und Anzeichen für chronische Leberveränderungen im Vergleich zu Patienten mit HIV/HCV-Koinfektion und HCV-Monoinfektion

    OpenAIRE

    Keim, Hannah

    2013-01-01

    Non-invasive assessment of liver-fibrosis in HIV monoinfected patients with signs of chronic liver disease compared to HIV/HCV-coinfected and HCV monoinfected patients Background: Elevated liver function tests (eLFT) in HIV monoinfected patients (pts) have been previously reported, caused by several medical conditions such as hepatic steatosis, non-alcoholic steatohepatitis (NASH) or drug toxicity. They may lead to liver fibrosis or portal hypertension. The best method to stage liver disea...

  10. HCV encephalopathy - an artefact due to medical care?

    Science.gov (United States)

    Weissenborn, K; Tillmann, H L

    2016-08-01

    Anti-HCV positive individuals frequently complain about chronic disabling fatigue, mood alterations and deficits in concentration and memory. Several data provide evidence that such alterations are unrelated to hepatitis C virus (HCV) viremia. Thus, merely being exposed to HCV in the past may be sufficient to trigger, but the HCV exposure itself. This commentary reviews the available data upon this topic with special reference to the paper by Lowry and colleagues published in this issue of the Journal of Viral hepatitis. We will carefully discuss scientific reasons, why HCV may be directly involved in the development of neuropsychiatric symptoms independent from ongoing detectable viremia, as suggested by epidemiological data. PMID:27225063

  11. Molecular Virology of Hepatitis C Virus (HCV: 2006 Update

    Directory of Open Access Journals (Sweden)

    2006-04-01

    Full Text Available Fascinating progress in the understanding of the molecular biology of hepatitis C virus (HCV was achieved recently. The replicon system revolutionized the investigation of HCV RNA replication and facilitated drug discovery. Novel systems for functional analyses of the HCV glycoproteins allowed the validation of HCV receptor candidates and the investigation of cell entry mechanisms. Most recently, recombinant infectious HCV could be produced in cell culture, rendering all steps of the viral life cycle, including entry and release of viral particles, amenable to systematic analysis. In this review, we summarize recent advances and discuss future research directions.

  12. Frequency of active HCV infection among anti-HCV positive patients in selected districts of Khyber Pakhtunkhwa, Pakistan

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    Sajid Ali

    2013-12-01

    Full Text Available Objective: The objective of this study was to determine frequency of active HCV infection among confirmed anti-HCV positive subjects of KPK in order to help the infected subjects decide about anti-viral treatment options. Methods: Blood samples (3075 samples were collected from patients in selected districts of KPK and were transported to Centre of Biotechnology and Microbiology, Diagnostic laboratory, University of Peshawar. These patients were already screened for anti-HCV by ICT (Immuno Chromatographic Technique and ELISA (Enzyme Linked Immunosorbant Assay in the local laboratories of the concern districts. Subsequently, viral RNA was isolated from serum sample and subjected to Real-time PCR. The frequency of the results was calculated for the HCV-RNA positive and negative samples. Results:Out of 3075 confirmed anti-HCV samples, HCV-RNA positive and negative samples were 2055 (66.6% and 1020 (33.3% respectively. The frequency of male and female HCV-RNA positive samples was 57.6% and 42.4% respectively. Rate of false anti-HCV positivity was 33.3%. Moreover, rate of active HCV infection was found more in district Bunir followed by districts Dir and Mardan. Comparatively less positive percent frequency of active HCV infection was found in districts Swabi, Peshawar and Kohat, respectively. Conclusion: It is concluded that viremia is present in more than 50% of confirmed anti-HCV positive patients. Anti-HCV positive, but HCV-RNA negative samples represent either false- positivity of anti-HCV or a spontaneous clearance of HCV.J Microbiol Infect Dis 2013;3(4: 199-202

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

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    John Rusine

    Full Text Available BACKGROUND: Data on prevalence and incidence of hepatitis B virus (HBV and hepatitis C virus (HCV infection in Rwanda are scarce. METHODS: 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 women initiating antiretroviral therapy (ART at baseline, and 200 women not yet eligible for ART. RESULTS: Baseline prevalence of active HBV infection (HBsAg positive, past or occult HBV infection (anti-HBc positive and HBsAg negative and anti-HCV was 5.2%, 42.9%, and 5.7%, respectively. The active HBV incidence rate was 4.2/1,000 person years (PY. In a multivariable logistic regression model using baseline data, participants with WHO stage 3 or 4 HIV disease were 4.19 times (95% CI 1.21-14.47 more likely to have active HBV infection, and older patients were more likely to have evidence of past exposure to HBV (aRR 1.03 per year; 95%CI 1.01-1.06. Older age was also positively associated with having anti-HCV antibodies (aOR 1.09; 95%CI 1.04-1.14 while having a higher baseline HIV viral load was negatively associated with HCV (aOR 0.60; 95% CI 0.40-0.98. The median CD4 increase during the first 12 months of ART was lower for those with active HBV infection or anti-HCV at baseline. Almost all participants (88% with active HBV infection who were on ART were receiving lamivudine monotherapy for HBV. CONCLUSION: HBV and HCV are common in HIV-infected patients in Rwanda. Regular HBsAg screening is needed to ensure that HIV-HBV co-infected patients receive an HBV-active ART regimen, and the prevalence of occult HBV infection should be determined. Improved access to HBV vaccination is recommended. Active HCV prevalence and incidence should be investigated further to determine whether HCV RNA PCR testing should be introduced in Rwanda.

  14. CD81 and Hepatitis C Virus (HCV Infection

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    Lucie Fénéant

    2014-02-01

    Full Text Available Hepatitis C Virus (HCV infection is a global public health problem affecting over 160 million individuals worldwide. Its symptoms include chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV is an enveloped RNA virus mainly targeting liver cells and for which the initiation of infection occurs through a complex multistep process involving a series of specific cellular entry factors. This process is likely mediated through the formation of a tightly orchestrated complex of HCV entry factors at the plasma membrane. Among HCV entry factors, the tetraspanin CD81 is one of the best characterized and it is undoubtedly a key player in the HCV lifecycle. In this review, we detail the current knowledge on the involvement of CD81 in the HCV lifecycle, as well as in the immune response to HCV infection.

  15. Characteristics of HCV co-infection among HIV infected individuals from an area with high risk of blood-borne infections in central China.

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    Tiejun Zhang

    Full Text Available OBJECTIVE: Hepatitis C virus (HCV and human immunodeficiency virus (HIV co-infection has been proved to be a growing public health concern. The prevalence and genotypic pattern vary with geographic locations. Limited information is available to date with regard to HCV genotype and its clinical implications among those former commercial blood donor communities. The aims of this study were to genetically define the HCV genotype and associated clinical characteristics of HIV/HCV co-infected patients from a region with commercial blood donation history in central China. METHODS: A cross sectional study, including 164 HIV infected subjects, was conducted in Shanxi province central China. Serum samples were collected and HCV antibody testing, AST and ALT testing were performed. Seropositive samples were further subjected to RT-PCR followed by direct sequence coupled with phylogenetic analysis of Core-E1 and NS5B regions performed in comparison with known reference genotypes. FINDINGS: A total of 139 subjects were HCV antibody positive. Genotype could be determined for 88 isolates. Phylogenetic analysis revealed that the predominant circulating subtype was HCV 1b (65.9%, followed by HCV 2a (34.1%. The HCV viral load in the subjects infected with HIV1b was significantly higher than those infected with HCV 2a (P = 0.006. No significant difference for HCV RNA level was detected between ART status, CD4+ cell count level and HIV RNA level. Serum AST and ALT level were likely to increase with HCV RNA level, although no significance was observed. Those who had conducted commercial donation later than 1991 (OR 3.43, 95% CI: 1.12-10.48 and had a short duration of donation (OR 0.35, 95% CI: 0.13-0.96 were more likely to be infected with HCV 1b. CONCLUSION: These results suggest that HCV subtype 1b predominates in this population, and the impact of HIV status and ART on HCV disease progression is not significantly correlated.

  16. Optimal treatment with boceprevir for chronic HCV infection.

    Science.gov (United States)

    Maasoumy, Benjamin; Manns, Michael P

    2013-02-01

    There are 160-170 million people with chronic hepatitis C virus (HCV) infection worldwide. The marketing of protease inhibitors (PIs) has been a milestone in the history of HCV therapy. In phase III studies, up to 75% of the patients achieved a sustained virological response (SVR) after triple therapy with pegylated-interferon (PEG-IFN)-α, ribavirin (RBV) and boceprevir (BOC). However, triple regimens are more expensive and associated with drug-drug interactions (DDIs) and more adverse events (AEs). According to results in 'real-world' settings, safety seems to be limited, in particular in patients with advanced liver disease. To optimize efficacy while minimizing AEs as well as costs, the optimal treatment strategy must be determined for BOC. Optimizing treatment is based on patient selection, the most efficient treatment design, management of side effects and the challenge of DDIs. Therapy-associated risks, treatment urgency and chances of SVR must all be considered for patient selection. In addition, certain differences between the two approved PIs may help identify the ideal candidates for each HCV PI. Optimal treatment design is based on the results of phase II and III studies, in which different approaches have been tested including 'lead-in' and response-guided strategies. Treatment regimens and stopping rules recommended by the FDA and EMA should normally be followed. Still, there are some cases in which more personalized strategies may be more promising. Management of side effects is a major challenge and plays a crucial role in ensuring safety and adherence. PMID:23286841

  17. Detection of HCV Core Antigen in the Diagnosis of Hepatitis C%丙肝病毒核心抗原的检测在诊断丙肝中的意义

    Institute of Scientific and Technical Information of China (English)

    刘胜林

    2014-01-01

    Objective Hepatitis C virus core antigen (HCV-cAg) was used to detect hepatitis C virus antibody (HCV-Ab), and quantitative detection of HCV-RNA, to explore the signiifcance of the hepatitis C virus core antigen testing for hepatitis C diagnosis. Methods 36 cases of hepatitis C antibody-positive patients and 120 cases of hepatitis C antibody-negative patients with simultaneous detection of HCV-Ab, HCV-cAg HCV-of RNA. HCV antibodies were detected by indirect ELISA, HCV core antigen detection by double antibody sandwich ELISA HCV of HCV-RNA was detected by fluorescent PCR assay for quantification. Results 36 cases of hepatitis C antibody-positive group, cAg of HCV-positive in 28 cases, 25 cases of HCV-RNA positive. The 120 cases of hepatitis C antibody negative out-patient hepatitis patients HCV-cAg in positive cases, HCV-RNA positive 1 cases. Conclusions Detection of HCV-cAg can shorten the window period of HCV antibody detection, high speciifcity, easy to operate, can be combined together to improve the detection of hepatitis C virus and accuracy.%目的:通过分别检测丙肝病毒抗体(HCV-Ab)、丙肝病毒核心抗原(HCV-cAg)和定量检测HCV-RNA,探究丙肝病毒核心抗原检测对于丙型肝炎诊断的意义。方法对36例丙肝抗体阳性患者和120例丙肝抗体阴性患者同时检测HCV-Ab、HCV-cAg和HCV-RNA。丙肝抗体检测采用间接ELISA法,丙肝核心抗原检测采用双抗体夹心ELISA法,丙肝HCV-RNA检测采用荧光PCR法定量检测。结果36例丙肝抗体阳性组中,HCV-cAg阳性28例,HCV-RNA阳性25例。120例丙肝抗体阴性的门诊肝炎患者中HCV-cAg阳性有2例,HCV-RNA阳性有1例。结论 HCV-cAg检测可以缩短HCV抗体检测窗口期,特异性高,操作简便,可将二者联合起来,提高丙型肝炎病毒的检出率及准确度。

  18. HCV virological response during treatment of chronic hepatitis C is associated with liver histological Improvement in patients with HCV/HIV co-infection

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    Gleusa Castro

    2008-06-01

    Full Text Available Liver histological improvement after treatment for chronic hepatitis C in patients co-infected with human immunodeficiency virus-1 (HIV-1 has been described. Paired liver biopsies in twenty six HCV/HIV co-infected patients were compared to determine factors possibly associated with histological improvement. The patients were submitted to a liver biopsy before treatment for hepatitis C and 25 months after the end of treatment. Fragments of the liver biopsy obtained before and after treatment were compared regarding the following parameters: histological activity index (HAI and degree of fibrosis (Knodell; intensity of collagen deposits (Sirius Red staining and degree of stellate cell activation (alpha-smooth muscle actin labeling. The ratios of the post and pre-treatment variables were related through logistic regression to body mass index (BMI, alcohol ingestion, HCV genotype, HCV viremia, presence of hepatic iron and pre-treatment hepatic steatosis. A negative RNA test in the 24th week of treatment was associated with improvement in fibrosis, collagen deposits and stellate cell numbers. The other variables analyzed did not correlate to an improvement in hepatic histology after hepatitis C treatment. Reduction in HCV viremia during treatment may result in reduced hepatic fibrosis even in patients without a sustained virological response.

  19. Rapid hepatitis C testing among persons at increased risk for infection--Wisconsin, 2012-2013.

    Science.gov (United States)

    Stockman, Lauren J; Guilfoye, Sheila M; Benoit, Andrea L; Vergeront, James M; Davis, Jeffrey P

    2014-04-11

    An estimated 3.2 million persons in the United States have chronic infection with hepatitis C virus (HCV). Most new HCV transmissions occur among persons who inject drugs, often within the first few years of their injection drug use. During 2003-2012, reports of HCV infection increased from 15 to 54 cases per 100,000 among persons aged HCV infection reported injecting drugs (Wisconsin Division of Public Health, unpublished data, 2013). To increase detection of HCV infection, the Wisconsin Division of Public Health (WDPH) piloted a program during October 2012-October 2013 that offered rapid HCV testing to clients of four agencies providing outreach testing for HCV and human immunodeficiency virus infection, syringe exchange, counseling, and other harm reduction services to persons with drug dependence. During that period, 1,255 persons were tested using a rapid HCV test, and 246 (20%) of the results were positive. Most (72%) of the infections had not been reported to WDPH. A blood specimen for further testing was collected from 192 (78%) participants with positive HCV test results; among these participants, 183 were tested for HCV RNA using reverse transcription-polymerase chain reaction (RT-PCR), and these results were positive for 128 (70%) participants, indicating active infection. Use of the rapid HCV test detected previously unreported HCV infections and raised awareness of HCV. Persons identified with active HCV infection should be referred to medical care and counseled on ways to prevent HCV transmission to others. PMID:24717818

  20. Clinical relevance of HCV antiviral drug resistance.

    Science.gov (United States)

    Welsch, C; Zeuzem, S

    2012-10-01

    The approval of direct-acting antiviral agents (DAAs) against the hepatitis C virus (HCV) NS3 protease revolutionized antiviral therapy in chronic hepatitis C. They mark the beginning of an era with drugs designed to inhibit specific viral proteins involved in the virus life cycle rather than the nonspecific antiviral activity of interferon. Upcoming generations of antivirals are expected that lead to viral eradication in most patients who undergo treatment with hope held for years that HCV can be cured without interferon. Antiviral drug resistance plays a key role in DAA-treatment failure. Knowledge on molecular escape mechanisms of resistant variants, their time to wild-type reversal and potential persistence is of upmost importance to design treatment strategies for patients with previous DAA-treatment failure. PMID:23006585

  1. 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; Soriano, V; Kirk, O; Knysz, B; Suetnov, O; Lazzarin, A; Ledergerber, B; Rockstroh, J K; Mocroft, A

    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....

  2. HCV-Related Nervous System Disorders

    OpenAIRE

    Salvatore Monaco; Sergio Ferrari; Alberto Gajofatto; Gianluigi Zanusso; Sara Mariotto

    2012-01-01

    Chronic infection with hepatitis C virus (HCV) is associated with a wide spectrum of extrahepatic manifestations, affecting different organ systems. Neurological complications occur in a large number of patients and range from peripheral neuropathy to cognitive impairment. Pathogenetic mechanisms responsible for nervous system dysfunction are mainly related to the upregulation of the host immune response with production of autoantibodies, immune complexes, and cryoglobulins. Alternative mecha...

  3. Aktuelles Management der HIV/HCV-Koinfektion

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    Payer BA

    2012-01-01

    Full Text Available Die HIV/HCV-Koinfektion findet sich sehr häufig bei HIV-Patienten mit intravenösem Drogenabusus. In dieser Patientengruppe stellt die HCV-assoziierte chronische Lebererkrankung heute auch die wichtigste Todesursache dar, da die HIV-Infektion meist sehr gut kontrolliert werden kann, die Hepatitis C aber oft nicht behandelt wird. Dabei sind die Therapieprinzipien sowohl für die HIV- als auch für die HCV-Infektion in der Zwischenzeit gut etabliert und auch allgemein akzeptiert: Eine retrovirale Therapie (cART sollte bei Koinfektion immer und unabhängig vom Immunstatus durchgeführt werden, da dies die Progression der Lebererkrankung positiv beeinflusst. Und die Hepatitis C sollte durch Standardtherapie mit Peginterferon plus Ribavirin therapiert werden, wobei in absehbarer Zeit auch bei Koinfektion die Dreifachtherapie mit den Proteaseinhibitoren Boceprevir und Telaprevir zum Einsatz kommen wird. Die Beachtung von Medikamenteninteraktionen wird dabei allerdings eine große Rolle spielen.

  4. Viral Hepatitis in Iranian Armed Forces: Prevalence of HBV and HCV in the Wounded-In-Action (WIA

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    Reza Yousefi-Arfaee

    2005-12-01

    Full Text Available Objective: Viral hepatitis remains a health threat to military forces. Most recently there has been concern abouthepatitis C virus transmission during military service. Hepatitis B and C are the main causes of mortality and morbidity in military personnel. Methods: In this study, all WIAs of two corps of Revolutionary Guards of IR. Iran were checked for hepatitis B and C and liver function tests (LFT. A questionnaire was filled out for all WIAs, in which risk factors were asked.Results: In this study, 563 WIAs were enrolled. Mean age was 38.9±3.9. Mean rate of disability was 25.5%. HBsAg positive prevalence was 4.8% and anti-HCV was 0.7%. In anti-HCV positive group, 50% had elevated enzymes and in HBsAg positive WIAs, 30.4% had elevated enzymes. All of HCV positive WIAs had surgery as a risk factor (100%. Conclusions: Based on the prevalence of anti-HCV positive, which shows a 5.5 times increase in prevalence of HCV in our study group, we recommend HCV infection screening in WIAs.

  5. New Tools in HCV Diagnosis, in Light of the Enhanced Awareness and the New Drugs for Treatment: SMARTube and Stimmunology

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    Svetlana Gorodin

    2013-01-01

    Full Text Available With improved HCV therapy, challenges regarding HCV diagnosis, such as seronegative window period, false positive readings, and differentiation between recent, chronic, and resolved infections, are of increasing importance. To address these challenges an innovative device—SMARTube HIV & HCV—was used. Blood samples were tested for anti-HCV antibodies before and after incubation in the SMARTube, which promotes the in vitro stimulation of in vivo HCV primed lymphocytes, thus enhancing levels of anti-HCV antibodies. Comparing antibody levels, in concordant samples before and after SMARTube, yielded the Stimulation Index (SI. Among 5888 fresh blood samples, from various populations and regions worldwide, 641 were seropositive using plasma, while SMARTube processing (yielding enriched plasma, termed SMARTplasma enabled diagnosis of 10 additional carriers in high-risk cohorts, that is, earlier detection. Using SMARTplasma eliminated all false positive results, using the current assays. In addition we show that SI calculation may serve as an important tool for differentiating between those who recently seroconverted, carriers of long-term infection, and those who have cleared the virus. SMARTube and the SI could lead to better, more informative diagnosis of HCV infections and play an important role in changing the way we treat both the infected individuals and the epidemic as a whole.

  6. The influence of HCV coinfection on clinical, immunological and virological responses to HAART in HIV-patients

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    Ricardo A. Carmo

    2008-06-01

    Full Text Available The potential impact of the hepatitis C virus (HCV on clinical, immunological and virological responses to initial highly active antiretroviral therapy (HAART of patients infected with human immunodeficiency virus (HIV is important to evaluate due to the high prevalence of HIV-HCV coinfection. A historical cohort study was conducted among 824 HIV-infected patients starting HAART at a public referral service in Belo Horizonte, Brazil, to assess the impact of HCV seropositivity on appearance of a new AIDS-defining opportunistic illness, AIDS-related death, suppression of viral load, and an increase in CD4-cell count. A total of 76 patients (9.2% had a positive HCV test, 26 of whom (34.2% had a history of intravenous drug use. In multivariate analysis, HCV seropositivity was associated with a smaller CD4-cell recovery (RH=0.68; 95% CI [0.49-0.92], but not with progression to a new AIDS-defining opportunistic illness or to AIDS-related death (RH=1.08; 95% CI [0.66-1.77], nor to suppression of HIV-1 viral load (RH=0.81; 95% CI [0.56-1.17] after starting HAART. These results indicate that although associated with a blunted CD4-cell recovery, HCV coinfection did not affect the morbidity or mortality related to AIDS or the virological response to initial HAART.

  7. A multicenter evaluation of the Abbott RealTime HCV genotype II assay

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    Marco Ciotti

    2009-12-01

    Full Text Available Viral genotype is an important determinant of the therapeutical outcome of the chronic hepatitis C and is useful in clinical practice to determine the duration of treatment1.While the viral type shows a clear association with therapeutic success, there is currently no evidence to that effect for HCV subtype, whose value is thus confined to epidemiological studies.The Abbott RealTime HCV Genotype II assay, through the use of Minor Groove Binder probes (MGB is able to distinguish genotypes 1 to 6 (target 5’-UTR region and subtypes 1a and 1b (NS5B region. In four different Italian centers a comparison between the Abbott RealTime HCV Genotype II assay and the Versant HCV Genotype 2.0 (LIPA has been performed.A total of 143 non selected samples with the request of HCV genotyping have been analysed. 141/143 samples (98.6% have provided reportable results with both tests (2 indeterminates with LIPA. Concordance at the type level was 96.5% (136/141. Considering the 136 concordant samples, the distribution was as follows: type 1 = 61 (44.9%, 2 = 36 (26.5%, 3 = 21 (15.4%, 4 = 17 (12.5% 5 = 1 (0.7%. Both assays assigned subtype in 56/61 (91.8% samples of genotype 1 (3 and 2 samples only provided the type for LIPA and Abbott, respectively and 50/56 (89.3% had concordant subtype. It is worth to note that 4 of the 5 samples with discordant subtype Abbott 1a/LiPA 1b came from the only center that used for LIPA the 5-UTR amplicon, loosing the benefit of the core region which has been introduced in the version 2 of the test to improve the accuracy in distinguishing between 1a and 1b.There was only one discordant sample at type level (Abbott 4, LIPA 1b which after sequencing and phylogenetic analysis was resolved as type 4. Four mixed infections were detected, 3 with the Abbott test (two 1a+4 and one 1b+3 and 1 with the LIPA test (1a+3. In all cases the comparison test showed a single genotype 1 infection. The new Abbott RealTime HCV Genotype II assay showed a

  8. Anti-HCV prevalence in firstyear students, that will practise professions of high risk of infection with the HCV

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    Penelope Siourda

    2007-07-01

    Full Text Available Aim: We have studied the prevalence of Hepatitis C on the first‐year students of the Paramedical Schools (Medical Lab Department, Nursing Department, Baby Nursing Department and Obstetrics Department of the Health and Foresight Professions School of Technological Educational School of Thessaloniki. Materials and Methods: The sample consists of 502 students of the Paramedical Schools. The students at first filled a questionnaire form (25 questions about the knowledge and the information in point of the infectious diseases in the Immunological – Hormonological Health Center. Then they gave blood sample and at the end, they were given a "Basic Guidebook for Preventing and Handling Hospital Infections". The samples were checked with ELISA method for anti‐HCV antibodies. Results: All the tests were negative for anti-HCV antibodies. Conclusions: It was ascertained that the prevalence of Hepatitis C on our target group is similar to the literature's known data (low in Greece. However since there is not a vaccine yet, anyone must be careful with Hepatitis C, specially the students of paramedical schools. Radical solution will be given inr the development of an appropriate vaccine.

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

    OpenAIRE

    John Lok Man Law; Chao Chen; Jason Wong; Darren Hockman; Santer, Deanna M; Frey, Sharon E.; Belshe, Robert B.; Takaji Wakita; Jens Bukh; Jones, Christopher T.; Rice, Charles M.; Sergio Abrignani; Lorne Tyrrell, D; Michael Houghton

    2013-01-01

    Although a cure for HCV is on the near horizon, emerging drug cocktails will be expensive, associated with side-effects and resistance making a global vaccine an urgent priority given the estimated high incidence of infection around the world. Due to the highly heterogeneous nature of HCV, an effective HCV vaccine which could elicit broadly cross-neutralizing antibodies has represented a major challenge. In this study, we tested for the presence of cross-neutralizing antibodies in human volun...

  10. 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.

  11. Endothelial Dysfunction Correlates with Liver Fibrosis in Chronic HCV Infection

    OpenAIRE

    Michele Barone; Maria Teresa Viggiani; Annabianca Amoruso; Serafina Schiraldi; Annapaola Zito; Fiorella Devito; Francesca Cortese; Michele Gesualdo; Natale Brunetti; Alfredo Di Leo; Pietro Scicchitano; Marco Matteo Ciccone

    2015-01-01

    Background. Hepatitis C virus (HCV) infection can exert proatherogenic activities due to its direct action on vessel walls and/or via the chronic inflammatory process involving the liver. Aims. To clarify the role of HCV in atherosclerosis development in monoinfected HCV patients at different degrees of liver fibrosis and with no risk factors for coronary artery disease. Methods. Forty-five patients were included. Clinical, serological, and anthropometric parameters, liver fibrosis (transient...

  12. Survey of both hepatitis B virus (HBsAg and hepatitis C virus (HCV-Ab coinfection among HIV positive patients

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    Pournia Yadollah

    2009-11-01

    Full Text Available Abstract Background HIV, HBVand HCV is major public health concerns. Because of shared routes of transmission, HIV-HCV coinfection and HIV-HBV coinfection are common. HIV-positive individuals are at risk of coinfection with HBV and HCV infections. The prevalence rates of coinfection with HBV and HCV in HIV-patients have been variable worldwide depending on the geographic regions, and the type of exposure. Aim This study aimed to examine HBV and HCV coinfection serologically and determine the shared and significant factors in the coinfection of HIV-positive patients. Methods This descriptive, cross-sectional study was carried out on 391 HIV-positive patients including 358 males and 33 females in Lorestan province, west Iran, to survey coinfection with HBsAg and anti-HCV. The retrospective demographic data of the subjects was collected and the patients' serums were analyzed by ELISA kits including HBsAg and anti-HCV. The collected data was analyzed with SPSS software (15 and Chi-square. Fisher's exact test with 5% error intervals was used to measure the correlation of variables and infection rates. Results The results of the study indicated that the prevalence of coinfection in HIV-positive patients with hepatitis viruses was 94.4% (370 in 391, out of whom 57 (14.5% cases were HBsAg positive, 282 (72% cases were anti-HCV positive, and 31 (7.9% cases were both HBsAg and anti-HCV positive. Conclusion There was a significant correlation between coinfection with HCV and HBV and/or both among HIV-positive patients depending on different variables including sex, age, occupation, marital status, exposure to risk factors.(p

  13. 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.

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

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    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

  15. 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.

  16. The role of HCV proteins on treatment outcomes.

    Science.gov (United States)

    Kumthip, Kattareeya; Maneekarn, Niwat

    2015-01-01

    For many years, the standard of treatment for hepatitis C virus (HCV) infection was a combination of pegylated interferon alpha (Peg-IFN-α) and ribavirin for 24-48 weeks. This treatment regimen results in a sustained virologic response (SVR) rate in about 50% of cases. The failure of IFN-α-based therapy to eliminate HCV is a result of multiple factors including a suboptimal treatment regimen, severity of HCV-related diseases, host factors and viral factors. In recent years, advances in HCV cell culture have contributed to a better understanding of the viral life cycle, which has led to the development of a number of direct-acting antiviral agents (DAAs) that target specific key components of viral replication, such as HCV NS3/4A, HCV NS5A, and HCV NS5B proteins. To date, several new drugs have been approved for the treatment of HCV infection. Application of DAAs with IFN-based or IFN-free regimens has increased the SVR rate up to >90% and has allowed treatment duration to be shortened to 12-24 weeks. The impact of HCV proteins in response to IFN-based and IFN-free therapies has been described in many reports. This review summarizes and updates knowledge on molecular mechanisms of HCV proteins involved in anti-IFN activity as well as examining amino acid variations and mutations in several regions of HCV proteins associated with the response to IFN-based therapy and pattern of resistance associated amino acid variants (RAV) to antiviral agents. PMID:26666318

  17. Permissiveness of human hepatoma cell lines for HCV infection

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    Sainz Bruno

    2012-01-01

    Full Text Available Abstract Background Although primary and established human hepatoma cell lines have been evaluated for hepatitis C virus (HCV infection in vitro, thus far only Huh7 cells have been found to be highly permissive for infectious HCV. Since our understanding of the HCV lifecycle would benefit from the identification of additional permissive cell lines, we assembled a panel of hepatic and non-hepatic cell lines and assessed their ability to support HCV infection. Here we show infection of the human hepatoma cell lines PLC/PRF/5 and Hep3B with cell culture-derived HCV (HCVcc, albeit to lower levels than that achieved in Huh7 cells. To better understand the reduced permissiveness of PLC and Hep3B cells for HCVcc infection, we performed studies to evaluate the ability of each cell line to support specific steps of the viral lifecycle (i.e. entry, replication, egress and spread. Results We found that while the early events in HCV infection (i.e. entry plus replication initiation are cumulatively equivalent or only marginally reduced in PLC and Hep3B cells, later steps of the viral life cycle such as steady-state replication, de novo virus production and/or spread are impaired to different degrees in PLC and Hep3B cultures compared to Huh7 cell cultures. Interestingly, we also observed that interferon stimulated gene (i.e. ISG56 expression was significantly and differentially up-regulated in PLC and Hep3B cells following viral infection. Conclusions We conclude that the restrictions observed later during HCV infection in these cell lines could in part be attributed to HCV-induced innate signaling. Nevertheless, the identification of two new cell lines capable of supporting authentic HCVcc infection, even at reduced levels, expands the current repertoire of cell lines amendable for the study of HCV in vitro and should aid in further elucidating HCV biology and the cellular determinants that modulate HCV infection.

  18. HIV and HCV discordant injecting partners and their association to drug equipment sharing.

    Science.gov (United States)

    De, Prithwish; Cox, Joseph; Boivin, Jean-Francois; Platt, Robert W; Jolly, Ann M; Alexander, Paul E

    2009-01-01

    Our objective was to examine the association between HIV and HCV discordant infection status and the sharing of drug equipment by injection drug users (IDUs). IDUs were recruited from syringe exchange and methadone treatment programmes in Montreal, Canada. Characteristics of participants and their injecting partners were elicited using a structured questionnaire. Among 159 participants and 245 injecting partners, sharing of syringes and drug preparation equipment did not differ between concordant or discordant partners, although HIV-positive subjects did not share with HIV-negative injectors. Sharing of syringes was positively associated with discordant HIV status (OR=1.85) and negatively with discordant HCV status (OR=0.65), but both results were not statistically significant. Sharing of drug preparation equipment was positively associated with both discordant HIV (OR=1.61) and HCV (OR=1.18) status, but both results were non-significant. Factors such as large injecting networks, frequent mutual injections, younger age, and male gender were stronger predictors of equipment sharing. In conclusion, IDUs do not appear to discriminate drug equipment sharing partners based at least on their HCV infection status. The results warrant greater screening to raise awareness of infection status, post-test counselling to promote status disclosure among partners, and skill-building to avoid equipment sharing between discordant partners. PMID:19172434

  19. Seroprevalences of HBV, HCV and HIV among Children who examined Before Elective Surgery in Mardin province

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    Tekin A et al.

    2011-10-01

    Full Text Available Objectives: The aim of this study was to investigate the seroprevalence of hepatitis B virus (HBV, hepatitis C virus (HCV and human immunodeficiency virus (HIV among children who examined before elective surgery in Mardin province. Materials and Methods: Between 01 November 2008 and 30 April 2010, a total of 556 patients aged 0–16 years, who planned to be operated, were investigated for viral hepatitis seroprevalences in the Mardin Women and Pediatrics Hospital. Children’s blood samples were tested for hepatitis B surface antigen (HBsAg, hepatitis B surface antibody (anti-HBs, HCV antibody (anti-HCV and HIV antibody (anti-HIV markers by chemiluminescent immunoassay with Advia Centaur (Siemens autoanalyser. Results: A total of 556 children (441 boys, 115 girls age under 16 years who planned to be underwent elective surgery were included. We found positive HBsAg and negative anti-HBs in 3 patients (0.5%; Negative HBsAg and positive anti-HBs were found in 473 children (85.1%; Negative HBsAg and negative anti-HBs were observed in 80 children (14.4%. None of the patients had positive HCV and HIV antibody. Conclusion: HBsAg positivity rate was lower and anti-HBs positivity rate was higher than expected levels. This study indicated that vaccination was successful in our region.

  20. A brief review on molecular, genetic and imaging techniques for HCV fibrosis evaluation

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    Sumrin Aleena

    2011-02-01

    Full Text Available Abstract Background Chronic HCV is one of the major causes of morbidity and mortality in the present day world. The assessment of disease progression not only provides useful information for diagnosis and therapeutic supervision judgment but also for monitoring disease. Different invasive and non invasive methods are applied to diagnose the disease from initial to end stage (mild fibrosis to cirrhosis. Although, liver biopsy is still considered as gold standard to identify liver histological stages, an assessment of the disease development based on non-invasive clinical findings is also emerging and this may replace the need of biopsy in near future. This review gives brief insight on non-invasive methods currently available for predicting liver fibrosis in HCV with their current pros and cons to make easier for a clinician to choose better marker to assess liver fibrosis in HCV infected patients. Methods More than 200 studies regarding invasive and noninvasive markers available for HCV liver disease diagnosis were thoroughly reviewed. We examined year wise results of these markers based on their sensitivity, specificity, PPV, NPV and AUROCs. Results We found that in all non-invasive serum markers for HCV, FibroTest, Forn's Index, Fibrometer and HepaScore have high five-year predictive value but with low AUROCs (0.60~0.85 and are not comparable to liver biopsy (AUROC = 0.97. Even though from its beginning, Fibroscan is proved to be best with high AUROCs (> 0.90 in all studies, no single noninvasive marker is able to differentiate all fibrosis stages from end stage cirrhosis. Meanwhile, specific genetic markers may not only discriminate fibrotic and cirrhotic liver but also differentiate individual fibrosis stages. Conclusions There is a need of marker which accurately determines the stage based on simplest routine laboratory test. Genetic marker in combination of imaging technique may be the better non invasive diagnostic method in future.

  1. Evaluation of new cases of HCV infection in thalassaemia patients for source of infection

    OpenAIRE

    Azarkeivan Azita; Nasiritoosi Mohsen; Kafiabad Sedigheh; Maghsudlu Mahtab; Hajibeigi Bashir; Hadizadeh Mohammad

    2011-01-01

    Background: Screening tests on blood bags is important step for blood safety. In Iran, screening for HCV started from 1996. We decided to determine the new cases of hepatitis C in our thalassemic patients, after screening of blood bags was initiated and trace backing from recipients to find their donors. Materials and Methods: The study was done on patients with complete files for HCVAb test results. Only cases that had a positive HCVAb result following a negative result were considered as ne...

  2. Expression and self-assembly of HCV structural proteins into virus-like particles and their immunogenicity

    Institute of Scientific and Technical Information of China (English)

    赵玮; 廖国阳; 蒋燕军; 姜述德

    2004-01-01

    Background The synthesis of virus-like particles (VLPs) provides an important tool to determine the structural requirements for viral particle assembly and virus-host interactions. Our purpose was to express simultaneously all three structural proteins of hepatitis C virus (HCV) in insect cells to investigate the proteins assembly into VLPs and the immunogenicity of these particles. Methods HCV gene sequences encoding the structural proteins C, E1, and E2 were amplified with PCR, and recombinant baculoviruses were constructed using recombinant DNA techniques. The expression of HCV structural proteins in insect cells was analyzed by immunofluoresceoce and SDS-PAGE. The interaction of expressed structural proteins was investigated by immunoprecipitation and immunoblotting. The VLPs in the insect cells were visualized by electron microscopy (EM). VLPs were then purified by sucrose gradient centrifugation and used to immunize BALB/c mice. Antibodies against HCV were tested for in mouse serum samples by an ELISA assay. Results The recombinant baculoviruses reBV/C and reBV/E1-E2 were constructed successfully. Insect cells co-infected with reBV/C and reBV/E1-E2 expressed HCV C, E1, and E2 proteins with the expected molecular weights of 20kD, 35kD, and 66kD, respectively. The results of immunoprecipitation and immunoblotting assays revealed the coimmunoprecipitation of C, E1, and E2 proteins, indicating association of the three structural proteins. Electron microscopy of insect cells co-infected with reBV/C and reBV/E1-E2 demonstrated spherical particles (40 to 60 nm in diameter) similar to the HCV virions from serum samples or hepatic tissue samples of HCV infected humans. The VLPs were partially purified. Antibodies to HCV were detectable in the serum of mice immunized with VLPs. Conclusion HCV structural proteins simultaneously expressed in insect cells can interact with each other and assemble into HCV-like particles, which are shown to be immunogenic in mice.

  3. lHCV-related burden of disease in Europe: a systematic assessment of incidence, prevalence, morbidity, and mortality

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    Siebert Uwe

    2009-01-01

    Full Text Available Abstract Background Hepatitis C virus (HCV is a leading cause of chronic liver disease, end-stage cirrhosis, and liver cancer, but little is known about the burden of disease caused by the virus. We summarised burden of disease data presently available for Europe, compared the data to current expert estimates, and identified areas in which better data are needed. Methods Literature and international health databases were systematically searched for HCV-specific burden of disease data, including incidence, prevalence, mortality, disability-adjusted life-years (DALYs, and liver transplantation. Data were collected for the WHO European region with emphasis on 22 countries. If HCV-specific data were unavailable, these were calculated via HCV-attributable fractions. Results HCV-specific burden of disease data for Europe are scarce. Incidence data provided by national surveillance are not fully comparable and need to be standardised. HCV prevalence data are often inconclusive. According to available data, an estimated 7.3–8.8 million people (1.1–1.3% are infected in our 22 focus countries. HCV-specific mortality, DALY, and transplantation data are unavailable. Estimations via HCV-attributable fractions indicate that HCV caused more than 86000 deaths and 1.2 million DALYs in the WHO European region in 2002. Most of the DALYs (95% were accumulated by patients in preventable disease stages. About one-quarter of the liver transplants performed in 25 European countries in 2004 were attributable to HCV. Conclusion Our results indicate that hepatitis C is a major health problem and highlight the importance of timely antiviral treatment. However, data on the burden of disease of hepatitis C in Europe are scarce, outdated or inconclusive, which indicates that hepatitis C is still a neglected disease in many countries. What is needed are public awareness, co-ordinated action plans, and better data. European physicians should be aware that many infections

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

    DEFF Research Database (Denmark)

    Bruggmann, P; Berg, T; Øvrehus, A L H;

    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...

  5. Socioeconomic status in HCV infected patients - risk and prognosis

    DEFF Research Database (Denmark)

    Omland, Lars Haukali Hvass; Osler, Merete; Jepsen, Peter;

    2013-01-01

    It is unknown whether socioeconomic status (SES) is a risk factor for hepatitis C virus (HCV) infection or a prognostic factor following infection.......It is unknown whether socioeconomic status (SES) is a risk factor for hepatitis C virus (HCV) infection or a prognostic factor following infection....

  6. HCV-related liver cancer in people with haemophilia

    NARCIS (Netherlands)

    Meijer, K.; Haagsma, E. B.

    2012-01-01

    . The topic of this monograph is liver cancer associated with chronic HCV infection. We start with some background information on chronic HCV infection and its long-term sequelae, one of which is liver cancer. The rest of the article is concerned with liver cancer or hepatocellular carcinoma (HCC).

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

    Directory of Open Access Journals (Sweden)

    John Lok Man Law

    Full Text Available Although a cure for HCV is on the near horizon, emerging drug cocktails will be expensive, associated with side-effects and resistance making a global vaccine an urgent priority given the estimated high incidence of infection around the world. Due to the highly heterogeneous nature of HCV, an effective HCV vaccine which could elicit broadly cross-neutralizing antibodies has represented a major challenge. In this study, we tested for the presence of cross-neutralizing antibodies in human volunteers who were immunized with recombinant glycoproteins gpE1/gpE2 derived from a single HCV strain (HCV1 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 genotypes. Although observed in only a minority of vaccinees, our results prove the key concept that a vaccine derived from a single strain of HCV can elicit broad cross-neutralizing antibodies against all known major genotypes of HCV and provide considerable encouragement for the further development of a human vaccine against this common, global pathogen.

  8. Interferon-λ in HCV Infection and Therapy  

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    Michael D. Robek

    2010-08-01

    Full Text Available Chronic infection with hepatitis C virus (HCV is associated with significant liver disease and is therefore an important public health problem. The current standard-of-care therapy for chronic HCV infection consists of a combination of pegylated (PEG interferon (IFN-α and ribavirin. Although this therapy effectively generates a sustained viral response in approximately half of treated individuals, it is associated with significant hematological and neurological side effects. A new family of IFN-related proteins (IFN-λ1, 2, and 3; or alternately, IL-29, 28A, 28B, respectively possesses properties that may make these cytokines superior to PEG-IFN-α for HCV therapy. Genetic studies have also implicated these proteins in both the natural and therapy-induced resolution of HCV infection. This review summarizes the basic aspects of IFN-λ biology, the potential role of these cytokines in HCV infection, and the outlook for their therapeutic application.

  9. Recent advances in the anti-HCV mechanisms of interferon

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    Menghao Huang

    2014-08-01

    Full Text Available Interferon (IFN in combination with ribavirin has been the standard of care (SOC for chronic hepatitis C for the past few decades. Although the current SOC lacks the desired efficacy, and 4 new direct-acting antiviral agents have been recently approved, interferons are still likely to remain the cornerstone of therapy for some time. Moreover, as an important cytokine system of innate immunity, host interferon signaling provides a powerful antiviral response. Nevertheless, the mechanisms by which HCV infection controls interferon production, and how interferons, in turn, trigger anti-HCV activities as well as control the outcome of HCV infection remain to be clarified. In this report, we review current progress in understanding the mechanisms of IFN against HCV, and also summarize the knowledge of induction of interferon signaling by HCV infection.

  10. An overview of HCV molecular biology, replication and immune responses

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    Nawaz Zafar

    2011-04-01

    Full Text Available Abstract Hepatitis C virus (HCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage, hepatocellular carcinoma and death. Currently, there is no vaccine available for prevention of HCV infection due to high degree of strain variation. The current treatment of care, Pegylated interferon α in combination with ribavirin is costly, has significant side effects and fails to cure about half of all infections. In this review, we summarize molecular virology, replication and immune responses against HCV and discussed how HCV escape from adaptive and humoral immune responses. This advance knowledge will be helpful for development of vaccine against HCV and discovery of new medicines both from synthetic chemistry and natural sources.

  11. Hepatitis C Virus (HCV) Prevalence in Special Populations and Associated Risk Factors: A Report From a Tertiary Hospital

    Science.gov (United States)

    Onyekwere, Charles Asabamaka; O Ogbera, Anthonia; Olusola Dada, Akinola; O Adeleye, Olufunke; O Dosunmu, Adedoyin; Akinbami, Akinsegun A; Osikomaiya, Bodunrin; Hameed, Oladipupo

    2016-01-01

    Background With the advent of highly effective anti-hepatitis C virus (HCV) drugs, efforts to identify infected cases, high-risk groups, and associated risk factors have become the focus of current control measures. Objectives To determine the prevalence of the HCV antibody among diabetics and patients with lymphoproliferative disorders (LPD) who presented to the outpatient clinics of a university hospital and its associated risk factors Patients and Methods Consecutively consenting patients who had been previously diagnosed with diabetes mellitus and LPD at the outpatient department of the Lagos State University teaching hospital were recruited. A case record form was used to extract their demographics and physical examination findings as well as any risk factors for HCV infection; blood was also drawn to run a serological assay for the HCV antibody. All data were collated and analyzed using the Statistical Package for the Social Sciences version 20. Student T-test, Chi square, and logistic regression were some of the inferential statistics used in addition to descriptive statistics. Results In all, 438 patients (405 diabetics and 33 patients with LPD) were recruited. Their ages ranged from 17 - 87 years with a mean + Standard deviation of 59.61 + 11.859 years. The prevalence of hepatitis C among the diabetic subgroup was 0.7%, while the antibody was present in 9.1% of the LPD patients. The occurrence of the HCV antibody was, however, not significantly associated with age, sex, educational level, or marital status (P > 0.05). Having multiple sexual partners was identified as the only significant risk factor for hepatitis C (OR = 9.148; P = 0.017). Conclusions This survey suggested that a higher HCV prevalence exists in this population than is currently reported in the general population, and having sex with multiple partners was a risk factor for HCV infection.

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

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    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. 第4代Murex HCV Ag/Ab联合检测试剂在血液筛查中的应用价值%Study on the possibility of the application of Murex HCV Ag/Ab combination (version 4.0) assay in blood

    Institute of Scientific and Technical Information of China (English)

    冷婵; 邱艳; 修冰水; 龚晓燕; 郑静; 查祎; 王全立

    2012-01-01

    Objective To investigate the application of the Murex HCV Ag/Ab combination (version 4.0) assay for blood screening. Methods 987 HCV-Ab reactive and gray zone samples were collected from routine blood screening and detected by both the Murex HCV Ag/Ab combination assay and Murex HCV Ab reagent. And verification test were carried out by RIBA and HCV NAT test. Results The positive rate of Murex HCV Ag/Ab combination assay and the Murex HCV Ab assay was 73.3% and 75.4% respectively, the negative rate was 95.8% and 90.8% and the final total positive rate was 85.8% and 84.0% respectively. The positive compliance rate between Murex HCV Ag/Ab combination and Murex HCV Ab assay was 76.7%, the negative compliance rate was is 94.5% and the total compliance rate was 87.6%. Among 123 inconsistent samples, 5 were RIBA negative /RNA positive,Murex HCV Ag/Ab positive for 4 samples (including confirmed window period sample); Murex HCV Ab was positive in only one sample; for 15 RIBA positive and RNA negative samples, 5 samples were positive by Murex HCV Ag/Ab and 10 samples were positive by Murex HCV Ab. Conclusions The RIBA negative and RNA positive samples could be efficiently detected out by Murex HCV Ag/Ab combination assay. Because the low compliance rate between Murex HCV Ag/Ab combination and Murex HCV Ab assay and the low detection rate of both system, we recommend the conjunction application of Murex HCV Ag/Ab combination and the Murex HCV Ab assay for blood screening. The double -check for HCV EIA blood screening strategy can help to reduce the possibility of transfusion transmitted infectious diseases.%目的 探讨第4代Murex HCV Ag/Ab联合检测试剂在血液筛查中的应用价值.方法 应用Murex HCV Ag/Ab联合检测试剂与Murex HCV Ab检测试剂,对987份血液筛查中HCV抗体初筛阳性和灰区标本及1份确认窗口期标本进行比较检测,应用RIBA、病毒核酸检测试剂进行补充验证实验,并对结

  14. 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

    2010-02-01

    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.

  15. Hepatitis C virus core, NS3, NS4B and NS5A are the major immunogenic proteins in humoral immunity in chronic HCV infection

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    Lappalainen Maija

    2009-06-01

    Full Text Available Abstract Background The viral genome of hepatitis C virus constitutes a 9.6-kb single-stranded positive-sense RNA which encodes altogether 11 viral proteins. In order to study the humoral immune responses against different HCV proteins in patients suffering from chronic HCV infection, we produced three structural (core, E1 and E2 and six nonstructural proteins (NS2, NS3, NS4A, NS4B, NS5A and NS5B in Sf9 insect cells by using the baculovirus expression system. Results The recombinant HCV core, E1, E2, NS2, NS3, NS4A, NS4B, NS5A and NS5B proteins were purified and used in Western blot analysis to determine antibody responses against individual HCV protein in 68 HCV RNA and antibody positive human sera that were obtained from patients suffering from genotype 1, 2, 3 or 4 infection. These sera were also analysed with INNO-LIA Score test for HCV antibodies against core, NS3, NS4AB and NS5A, and the results were similar to the ones obtained by Western blot method. Based on our Western blot analyses we found that the major immunogenic HCV antigens were the core, NS4B, NS3 and NS5A proteins which were recognized in 97%, 86%, 68% and 53% of patient sera, respectively. There were no major genotype specific differences in antibody responses to individual HCV proteins. A common feature within the studied sera was that all except two sera recognized the core protein in high titers, whereas none of the sera recognized NS2 protein and only three sera (from genotype 3 recognised NS5B. Conclusion The data shows significant variation in the specificity in humoral immunity in chronic HCV patients.

  16. Expression and immunoreactivity of HCV/HBV epitopes

    Institute of Scientific and Technical Information of China (English)

    Xin-Yu Xiong; Xiao Liu; Yuan-Ding Chen

    2005-01-01

    AIM: To develop the epitope-based vaccines to prevent Hepatitis C virus (HCV)/Hepatitis B virus (HBV) infections.METHODS: The HCV core epitopes C1 STNPKPQRKTKRNTNRRPQD (residuals aa2-21) and C2 VKFPGGGQIVGGVYLLPRR (residuals aa22-40), envelope epitope E GHRMAWDMMMNWSP (residuals aa315-328) and HBsAg epitope S CTTPAQGNSMFPSCCCTKPTDGNC (residuals aa124-147) were displayed in five different sites of the flock house virus capsid protein as a vector, and expressed in E. coli cells (pET-3 system).Immunoreactivity of the epitopes with anti-HCV and anti-HBV antibodies in the serum from hepatitis C and hepatitis B patients were determined.RESULTS: The expressed chimeric protein carrying the HCV epitopes C1, C2, E (two times), L3C1-I2E-L1C2-L2E could react with anti-HCV antibodies. The expressed chimeric protein carrying the HBV epitopes S, I3S could react with anti-HBs antibodies. The expressed chimeric proteins carrying the HCV epitopes C1, C2, E plus HBV epitope S, L3C1-I2E-L1C2-L2E-I3S could react with antiHCV and anti-HBs antibodies.CONCLUSION: These epitopes have highly specific and sensitive immunoreaction and are useful in the development of epitope-based vaccines.

  17. Frequency of anti-HCV, Hbsag and related risk factors in pregnant women at Nishtar Hospital, Multan

    International Nuclear Information System (INIS)

    Background: Viral hepatitis is a global issue. Among the hepatitis viruses hepatitis B and C are important in South Asia including Pakistan. There are various modes of transmission of these viruses. Vertical transmission is also gaining importance. Antepartum screening for HBV and HCV would help the infected women for appropriate antiviral therapy at appropriate time as well as for taking proper care of the newborns. The present study was designed to see the frequency of HBsAg and anti-HCV in pregnant women at Nishtar Hospital, Multan. Methods: This was a cross-sectional study carried out using non-probability purposive sampling technique. The period of the study was from June 2006 to August 2007. Five hundred (500) pregnant women attending outpatient department of Gynaecology and Obstetrics were included. Informed consent was taken. A specially designed proforma was filled in. Anti-HCV and HBsAg were tested by device method. Data were analyzed on SPSS-11. Results: Out of 500 pregnant women 35 (7.00%) were found to be anti-HCV positive and 23 (4.60%) were positive for HBsAg. Mean age was 26.7+-4.8 years. Majority of the patients 263 (52.60%) were in the age group 26-35 years. 138 (27.60%) women were nulliparous and 282 (56.40%) were para 1-4 and anti-HCV and HBsAg were common in this parity group. Only 80 (16.00%) women were para 5 or more. All anti-HCV and HBsAg positive women were house-wives. Most of them were belonging to rural areas having poor socio-economic status. Among 35 anti-HCV positive women, 20 (57.14%) had history of previous surgery, while 13 (37.14%) had history of multiple injections, 5 (14.28%) received blood transfusion, 4 (11.42%) had ear/nose piercing while tattooing was seen in only 2 (5.71%). Among 23 HBsAg positive women, 10 (43.47%) had history of previous surgery. History of multiple injections was present in 6 (26.08%) patients, 4 (17.39%) patients had history of blood transfusion, tattooing, ear/nose piercing, history of dental

  18. 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...

  19. Automated Triplex (HBV, HCV and HIV) NAT Assay Systems for Blood Screening in India

    Science.gov (United States)

    2016-01-01

    This review is confined to triplex nucleic acid testing (NAT) assays to be used on fully automated platform. Around the world, these assays are being used at various transfusion medicine centres or blood banks to screen blood units for HBV, HCV and HIV. These assay systems can screen up to 1000 blood units for HBV, HCV and HIV simultaneously in a day. This area has been dominated by mainly two manufacturers: M/s Gen-Probe-Novartis and M/s Roche Molecular Systems. The triplex NAT assay systems of both manufacturers are licensed by United States Food and Drug Administration. There is not much awareness about the technology and procedures used in these assays. The main objective of this review is to create awareness about the technology and procedure of these assays. PMID:27042485

  20. Affinity-Based Screening Technology and HCV Drug Discovery

    Institute of Scientific and Technical Information of China (English)

    LI Bin

    2003-01-01

    @@ NS5A is one of the non-structural gene products encoded by Hepatitis C virus (HCV) and related viruses that are essential for viral replication. The amino acid sequence of NS5A is conserved between different HCV genotypes and the primary amino acid sequence of NS5A is unique to HCV and closely related viruses. Importantly, NS5A is unrelated to any human protein. This indicates that drugs designed to block the actions of NS5A could inhibit the replication of HCV without showing toxic side effects in human host cells, thus making NS5A inhibitors ideal anti-viral drugs. However, there are presently no functional assays for this essential viral protein. Therefore, conventional high throughput screening (HTS) approaches can not be used to discover antiviral drugs against NS5A.

  1. Seropositivity of HBsAg, anti-HCV and anti-HIV in preoperative patients

    Directory of Open Access Journals (Sweden)

    Berrin Karaayak Uzun

    2014-12-01

    Full Text Available Objective: The infections caused by human immunodeficiency virus (HIV, hepatitis B (HBV and C (HCV viruses pose a serious occupational risk for the healthcare workers especially those in emergency services, laboratories and surgery wards. Vaccination and establishment of the strict biosafety procedures are the main principles to prevent blood-borne infections in healthcare workers. Additionally, serological screening of the preoperative patients could decrease the risk for exposure. In this study, we aimed to determine the seroprevalence of HBsAg, anti-HCV, anti-HIV 1/2 in preoperative patients. Methods: Hospital automation records were evaluated retrospectively for 4.367 patients who were scheduled for surgery and scanned for anti-HIV 1/2, HBsAg and anti-HCV as preoperative procedures in the preparation period of operation between January 2012 and December 2012. Results: HBsAg positivity rate was found in 7.7% (n=336, anti-HCV positivity rate was found in 2.3% (n=101. A two (0.05% of five patients were positive for anti-HIV 1/2 was found positive verification test and the other three samples were accepted as false positive test results. Conclusion: All healthcare workers must be trained about occupational diseases and vaccinated against Hepatitis B. Universal precautions must be strictly followed particularly in the operating room. In addition, all patients should be considered as potential carriers regarded as a carrier of the potential for infection. J Clin Exp Invest 2013; 4 (4: 449-452

  2. Prevalence and risk factors of Hepatitis C among individuals presenting to HIV testing centers, Hawassa city, Southern Ethiopia

    Directory of Open Access Journals (Sweden)

    Sisay Zufan

    2011-06-01

    Full Text Available Abstract Background Hepatitis C virus (HCV, either alone or in combination with Human Immunodeficiency virus (HIV, constitutes a major public health concern. This study was conducted to describe the prevalence and risk factors for HCV infection in people with and without HIV infection. Methods Blood samples and data on socio-demographic and risk factors for HCV infection were collected from consecutive 400 HIV- positive and 400 HIV- negative individuals attending HIV testing centers in Hawassa city, from October to December, 2008. All sera were tested for antibody to HCV infection (anti-HCV using enzyme linked immunosorbent assay (ELISA. Sera positive for anti-HCV were further tested for viral ribonucleic acid (RNA levels using real-time polymerase chain reaction. Results The rate of anti-HCV positivity was 10.5% in the HIV- infected individuals compared with 6% in the HIV negative group (p = 0.002. HCV-RNA was detected in 9.1% of anti-HCV positive samples and rates were comparable between HIV- infected and HIV- non-infected individuals. There was no significant difference in odds of HCV infection in participants with and without HCV risk factors in either HIV sero-group. Conclusion HIV infected individuals had significantly higher rate of anti-HCV although most of them showed no evidence of viraemia. Hence, while priority should be given for HIV infected patients, testing those with anti-HCV for HCV-RNA remains important.

  3. Hepatitis C virus (HCV) genotypes in 373 Italian children with HCV infection: changing distribution and correlation with clinical features and outcome

    OpenAIRE

    Bortolotti, F; Resti, M; Marcellini, M; Giacchino, R.; Verucchi, G.; Nebbia, G; Zancan, L; Marazzi, M G; Barbera, C; Maccabruni, A; Zuin, G.; Maggiore, G; Balli, F.; Vajro, P; Lepore, L

    2005-01-01

    Background and aim: Little is known of hepatitis C virus (HCV) genotypes in HCV infected children. This retrospective, multicentre study investigated genotype distribution and correlation with clinical features and outcome in a large series of Italian children.

  4. Small molecule inhibitors of HCV replication from Pomegranate

    Science.gov (United States)

    Reddy, B. Uma; Mullick, Ranajoy; Kumar, Anuj; Sudha, Govindarajan; Srinivasan, Narayanaswamy; Das, Saumitra

    2014-06-01

    Hepatitis C virus (HCV) is the causative agent of end-stage liver disease. Recent advances in the last decade in anti HCV treatment strategies have dramatically increased the viral clearance rate. However, several limitations are still associated, which warrant a great need of novel, safe and selective drugs against HCV infection. Towards this objective, we explored highly potent and selective small molecule inhibitors, the ellagitannins, from the crude extract of Pomegranate (Punica granatum) fruit peel. The pure compounds, punicalagin, punicalin, and ellagic acid isolated from the extract specifically blocked the HCV NS3/4A protease activity in vitro. Structural analysis using computational approach also showed that ligand molecules interact with the catalytic and substrate binding residues of NS3/4A protease, leading to inhibition of the enzyme activity. Further, punicalagin and punicalin significantly reduced the HCV replication in cell culture system. More importantly, these compounds are well tolerated ex vivo and`no observed adverse effect level' (NOAEL) was established upto an acute dose of 5000 mg/kg in BALB/c mice. Additionally, pharmacokinetics study showed that the compounds are bioavailable. Taken together, our study provides a proof-of-concept approach for the potential use of antiviral and non-toxic principle ellagitannins from pomegranate in prevention and control of HCV induced complications.

  5. Cryoglobulinemia in elderly patients with HCV-related chronic hepatitis

    Institute of Scientific and Technical Information of China (English)

    Francesco; Giuseppe; Foschi; Anna; Chiara; Dall’Aglio; Arianna; Lanzi; Giorgio; Marano; Sara; Savini; Pietro; Andreone; Mauro; Bernardi; Giuseppe; Francesco; Stefanini

    2010-01-01

    Hepatitis C virus(HCV) infection affects about 3% of the world’s population and often leads to chronic liver disease.In some industrialized countries,HCV prevalence increases with age,but the optimal management of older patients has not been accurately defined.HCV infection can also lead to lymphoproliferative disorders,the most common being mixed cryoglobulinemia(MC),and also for this condition that frequently affects elderly patients,the optimal therapeutic strategy is still debated.We report the case of a 77-year-old Caucasian woman with HCV-related chronic hepatitis and cutaneous manifestations consisting of urticaria and pruritus related to MC resistant to antihistamines.The patient underwent a treatment with interferon and ribavirin.Such a treatment led to early biochemical and virological response associated with the resolution of cryoglobulinemia and cutaneous symptoms.After the end of treatment,HCV replication relapsed,but cryoglobulinemia and cutaneous symptoms did not recur.In the absence of definite treatment guidelines in this particular context,our experience suggests that the presence of symptoms related to HCV-infection that deeply affect patient quality of life warrants antiviral therapy even beyond the age limits that currently exclude patients from treatment.

  6. Nursing Problems in Care of a Patient with Very Early HCV Infection Recurrence After Liver Transplantation: A Case Report.

    Science.gov (United States)

    Hreńczuk, Marta; Sowińska, Renata; Tronina, Olga; Małkowski, Piotr; Durlik, Magdalena; Pacholczyk, Marek; Kosieradzki, Maciej

    2016-01-01

    BACKGROUND Recurrent HCV infection following liver transplantation is a common problem, and usually has a more aggressive course than primary infection. The aim of the paper was to present nursing problems in the care of a 22-year-old female patient after liver transplantation (Ltx) with a rapid recurrence of HCV infection shortly after Ltx. CASE REPORT Ltx was performed 22 July 2012 due to chronic cirrhosis secondary to HCV infection with viremia (HCV PCR 3.5×107 IU/mL). Graft function worsened 14 days following transplantation. Acute cholestatic hepatitis related to HCV reinfection was diagnosed based on biopsy. During a period of 20 months the patient received 3 different antiviral treatment regimens, beginning with a dual therapy (Interferon and Ribavirin), followed by the inclusion of Telaprevir, then Daclatasvir; however, these treatments were not successful. The fourth-line regimen with sofosbuvir (EU medical experiment) led to viremia elimination (HCV PCR) after 5 weeks of treatment. However, hepatic failure stabilization was unsuccessful, there was an increase in encephalopathy, and the MELD score was 25. Therefore, the patient underwent liver retransplantation. In the post-transplantation period, the patient was in good condition, with no viremia. CONCLUSIONS The most common nursing problems in the care of the patient were associated with the diagnostic process, therapies used (including experimental treatment), and progressive liver failure. The therapeutic success should be attributed to the intensive supervision and monitoring of viremia, immediate inclusion of adequate treatment methods, adequate patient preparation for diagnostic tests, and careful care after diagnostics, as well as psychological support and education. PMID:27357745

  7. Risk Factors for Hepatitis C Virus (HCV) Infection in Areas with a High Prevalence of HCV in the Republic of Korea in 2013

    OpenAIRE

    Sohn, Hae-Sook; Kim, Jang Rak; Ryu, So Yeon; Lee, Youn-Jae; Lee, Myeong Jin; Min, Hyun Ju; Lee, Jun; Choi, Hwa Young; Song, Yeong Jun; Ki, Moran

    2016-01-01

    Background/Aims The prevalence of hepatitis C virus (HCV) infection in Busan, Gyeongnam, and Jeonnam Provinces in Korea is more than twice the national average. This study aimed to examine whether demographic and lifestyle characteristics are associated with HCV infection in these areas. Methods A case control study was performed at three study hospitals. HCV cases were matched with two controls for sex and age. Patient controls were selected from non-HCV patients at the same hospital. Health...

  8. Factors associated with liver biopsy performance in HCV-HIV coinfected injecting drug users with HCV viremia: Results from a five-year longitudinal assessment

    OpenAIRE

    Rey, Dominique; Carrieri, Maria-Patrizia; Spire, Bruno; Loubière, Sandrine; Dellamonica, Pierre; Gallais, Hervé; Cassuto, Gilles-Patrice; Gastaut, Jean-Albert; Obadia, Yolande

    2004-01-01

    The last international consensus conference about hepatitis C virus (HCV) treatment emphasized the importance of treatment for persons coinfected with HCV and human immunodeficiency virus (HIV). As liver biopsy precedes treatment, we aimed to identify factors associated with the performance of liver biopsy among HIV-HCV coinfected drug users during a 5-year follow-up to study their access to HCV treatment. Of the 296 patients followed in the HIV hospital departments of Nice and Marseilles and...

  9. Expression of core antigen of HCV genotype 3a and its evaluation as screening agent for HCV infection in Pakistan

    OpenAIRE

    Rehman Irshad U; Saleem Zafar; Idrees Muhammad; Yousaf Muhammad Z; Ali Muhammad

    2011-01-01

    Abstract Background Pakistan is facing a threat from hepatitis C infection which is increasing at an alarming rate throughout the country. More specific and sensitive screening assays are needed to timely and correctly diagnose this infection. Methods After RNA extraction from specimen (HCV-3a), cDNA was synthesized that was used to amplify full length core gene of HCV 3a. After verification through PCR, DNA sequencing and BLAST, a properly oriented positive recombinant plasmid for core gene ...

  10. DCs pulsed with novel HLA-A2-restricted CTL epitopes against hepatitis C virus induced a broadly reactive anti-HCV-specific T lymphocyte response.

    Directory of Open Access Journals (Sweden)

    Zhongsheng Guo

    Full Text Available OBJECTIVE: To determine the capacity of dendritic cells (DCs loaded with single or multiple-peptide mixtures of novel hepatitis C virus (HCV epitopes to stimulate HCV-specific cytotoxic T lymphocyte (CTL effector functions. METHODS: A bioinformatics approach was used to predict HLA-A2-restricted HCV-specific CTL epitopes, and the predicted peptides identified from this screen were synthesized. Subsequent IFN-γ ELISPOT analysis detected the stimulating function of these peptides in peripheral blood mononuclear cells (PBMCs from both chronic and self-limited HCV infected subjects (subjects exhibiting spontaneous HCV clearance. Mature DCs, derived in vitro from CD14(+ monocytes harvested from the study subjects by incubation with appropriate cytokine cocktails, were loaded with novel peptide or epitope peptide mixtures and co-cultured with autologous T lymphocytes. Granzyme B (GrB and IFN-γ ELISPOT analysis was used to test for epitope-specific CTL responses. T-cell-derived cytokines contained in the co-cultured supernatant were detected by flow cytometry. RESULTS: We identified 7 novel HLA-A2-restricted HCV-specific CTL epitopes that increased the frequency of IFN-γ-producing T cells compared to other epitopes, as assayed by measuring spot forming cells (SFCs. Two epitopes had the strongest stimulating capability in the self-limited subjects, one found in the E2 and one in the NS2 region of HCV; five epitopes had a strong stimulating capacity in both chronic and self-limited HCV infection, but were stronger in the self-limited subjects. They were distributed in E2, NS2, NS3, NS4, and NS5 regions of HCV, respectively. We also found that mDCs loaded with novel peptide mixtures could significantly increase GrB and IFN-γ SFCs as compared to single peptides, especially in chronic HCV infection subjects. Additionally, we found that DCs pulsed with multiple epitope peptide mixtures induced a Th1-biased immune response. CONCLUSIONS: Seven novel and

  11. Efficacy and safety of etravirine-containing regimens in a large cohort of HIV/HCV coinfected patients according to liver fibrosis

    Directory of Open Access Journals (Sweden)

    Jose Luis Casado

    2014-11-01

    advanced fibrosis was not associated to a higher risk of etravirine discontinuation (26% vs 21%; p=0.27, log-rank test or virologic failure (9% vs 11%, p=0.56. CD4+ cell count increase was lower in HCV patients (+23 vs +86 at 6 month; p=0.02. Conclusions: Etravirine is safe in HIV/HCV coinfected patients, even in presence of moderate and advanced liver fibrosis and as part of different antiretroviral regimens.

  12. People with multiple tattoos and/or piercings are not at increased risk for HBV or HCV in The Netherlands.

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    Anouk T Urbanus

    Full Text Available BACKGROUND: Although published results are inconsistent, it has been suggested that tattooing and piercing are risk factors for HBV and HCV infections. To examine whether tattooing and piercing do indeed increase the risk of infection, we conducted a study among people with multiple tattoos and/or piercings in The Netherlands who acquired their tattoos and piercings in The Netherlands and/or abroad. METHODS: Tattoo artists, piercers, and people with multiple tattoos and/or piercings were recruited at tattoo conventions, shops (N = 182, and a biannual survey at our STI-outpatient clinic (N = 252 in Amsterdam. Participants were interviewed and tested for anti-HBc and anti-HCV. Determinants of HBV and HCV infections were analysed using logistic regression analysis. RESULTS: The median number of tattoos and piercings was 5 (IQR 2-10 and 2 (IQR 2-4, respectively. Almost 40% acquired their tattoo of piercing abroad. In total, 18/434 (4.2%, 95%CI: 2.64%-6.46% participants were anti-HBc positive and 1 was anti-HCV positive (0.2%, 95%CI: 0.01%-1.29%. Being anti-HBc positive was independently associated with older age (OR 1.68, 95%CI: 1.03-2.75 per 10 years older and being born in an HBV-endemic country (OR 7.39, 95%CI: 2.77-19.7. Tattoo- and/or piercing-related variables, like having a tattoo or piercing in an HBV endemic country, surface percentage tattooed, number of tattoos and piercings etc., were not associated with either HBV or HCV. CONCLUSIONS: We found no evidence for an increased HBV/HCV seroprevalence among persons with multiple tattoos and/or piercings, which might be due to the introduction of hygiene guidelines for tattoo and piercing shops in combination with the low observed prevalence of HBV/HCV in the general population. Tattoos and/or piercings, therefore, should not be considered risk factors for HBV/HCV in the Dutch population. These findings imply the importance of implementation of hygiene guidelines in other countries.

  13. Screening of HBsAg and anti HCV from tertiary care, private and public sector hospitals

    International Nuclear Information System (INIS)

    Objectives: To find out the frequency of hepatitis B surface antigen and hepatitis C antibodies in patients referred from a tertiary care public sector hospital, other public sector and private hospitals of Karachi. Settings and duration: Pakistan Medical Research Council's Specialized Research Centre for Gastroenterology and Hepatology, at Jinnah Postgraduate Medical Centre Karachi from January to December 2009. Patients and Methods: A cross sectional study was conducted where patients were referred from different departments of Jinnah Postgraduate Medical Centre (tertiary care public sector hospital), other public sector hospitals, private hospitals and clinics for the screening of hepatitis B and C virus infection. Three ml blood was collected from each patient, serum separated and tested for HBsAg and Anti HCV using Abbott Murex fourth Generation ELISA kits. Results: A total of 2965 cases were referred in a year. Overall sero prevalence of HBsAg and Anti-HCV was 5.9% and 12.8% respectively. HBsAg positivity in patient referred from public sector hospitals was 5.8%, those from private hospitals/clinics were 7.2%, and self-referred patients was 5.6%. Anti HCV positivity rates amongst these cases were 12.5%, 16.7% and 8.5% respectively. Co-infection of hepatitis B virus and hepatitis C virus was seen in 0.9, 2.5 and 1.4% cases respectively. Breakdown of viral positivity within different departments of Jinnah Postgraduate Medical Centre Karachi showed HBsAg positivity of 7.1% in Medical department, 5.2% in Surgical department, 5.0% in Gynaecology department, 6.6% in other departments of Jinnah Postgraduate Medical Centre while, only 1.7% were positive from Pakistan Railway, hospital Anti HCV positivity was maximally (20.3%) seen in medical department followed by 14% in other departments, 10.9% in surgical department, 7.9% in gynaecology and 5.1% in railway hospital. Co-infection of HBV and HCV was seen in 2% cases referred from medical department, while rest of the

  14. Insights on treatment of a Portuguese cohort of HCV/HIV coinfected patients

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    C Silva

    2012-11-01

    Full Text Available Purpose of the study: This study intends to characterize a Portuguese patient population with chronic HCV and HIV coinfection, followed at our Research Unit, underline the importance of early treatment and incorporate the importance of DDA for retreatment of HCV infection. Methods: Retrospective, observational analysis of medical records of 348 HCV/HIV coinfected patients from 2001 to 2011. Demographic, epidemiological, clinical and laboratory data and virologic response were collected. Summary of results: Review of 348 HCV/HIV coinfected patients, 121 of those (34.7% under treatment, predominantly male (77.0% and Caucasians (94.8% with a median age of 44 yrs old (min 25; max 77 yrs. Intravenous drug use was the main route of HCV infection, in 71.3% of patients, and 8.3% were related with MSM. Frequent morbidities were alcohol abuse (46.8%, illicit drug use (70.1%, methadone (25.6% and mental disturbances (12.3% of patients. Regarding HIV infection, six were HIV-2 and 342 HIV-1; 36.1% were stage A and 29.6% were stage C (CDC Atlanta, 94.8% on antiretroviral treatment and only 21.9% of them with more than 350 TCD4 cell count. Genotype 1 was the most prevalent (58.1%–117 genotype 1a, 26 genotype 1b; 1.6% were genotype 2, 22.8% genotype 3 and 17.5% genotype 4. Previous to treatment initiation, HCV ARN was above 600.000 IU/mL in 56.9% patients. Fibrosis was evaluated by fibroelastography in 41.1% and hepatic biopsy in 26.3% of patients; in those, 44.0% had a score above F2 (METAVIR and ALT was elevated 2 times the limit in 38.0%, with an average value of 94 UI/L. IL 28B testing was performed in only 35 patients at the time, with 45.7% CC and 17.1% CT genotype. Treatment was started in 34.8% of patients, with 1.7 treatments per individual, and regimen was based on peguilated interferon with ribavirin in 93.6% of cases (72.1% with peginterferon alfa 2a. The SVR rate was 51.2%, with 28.9% non responders, 3 relapsers and 9 treatment interruptions due

  15. The effects of Maraviroc on liver fibrosis in HIV/HCV co-infected patients

    Directory of Open Access Journals (Sweden)

    Enrique Ortega Gonzalez

    2014-11-01

    Full Text Available Introduction: The fibrogenesis analysis in quimeric CCR1 and CCR5 mice revealed that CCR5 mediates its pro-fibrogenic effects in hepatic cells and promoting stellate cells. The blockage of co-receptors could preserve the progression of hepatic fibrosis in HIV/HCV co-infected patients. Objective: To evaluate the beneficial effects on hepatic fibrosis in HIV/HCV co-infected patients that are on antiretroviral therapy (ART with CCR5 co-receptor antagonists. Method and materials: A multicentre, retrospective pilot study of the evaluation of hepatic fibrosis at mid- and long-term by non-invasive methods in a HIV/HCV co-infected patients cohort in the Valencian Community (Spain that received ART with a CCR5 co-receptor antagonist. The cut-off points of serum marker tests of hepatic fibrosis were: AST to Platelet Ratio Index (APRI1.5 F2; >2 Cirrhosis and Forns Index6.9>F2 fibrosis. Inclusion criteria was established for HIV/HCV co-infected patients on ART with CCR5 co-receptor antagonists that had no previous history of interferon and ribavirin treatment or those who were null-responders and received CCR5 co-receptor antagonist treatment in the previous year. Patients with HBV infection were excluded. Results: A total of 71 male patients (69% were reported. A CD4 nadir 350 cells/uL. According to genotypes, 50% were G-1a, 14% G-1b, 11% G-3 and 25% G-4. The median duration of treatment with Maraviroc (MVC was the following: 45% took it over a year, 41% over two years and 14% over three years. Before starting treatment with MVC, we observed an initial fibrosis of F0–F1 in 49% of patients, F2–F3 in 24% and F4 in 27%. The medium follow-up was of 18.45 months. Progression to a higher fibrosis level was observed in five patients, 11 patients improved at least one stage and the others were stable over time. There were 38 patients taking MVC over two years, 27 patients in this group (59.38% did not modify their fibrosis, 3 patients (11% progressed and 8 (29

  16. Liver Fibrosis progression using Fibroscan in HIV/HCV coinfected patients with undetectable HIV viral load

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    Laura Perez-Martinez

    2014-11-01

    Full Text Available Introduction: Several factors such as duration of infection, age, male gender, consumption of alcohol, HIV infection and low CD4 count have been associated with fibrosis progression rate. However, it is relatively scarce, the knowledge about the liver fibrosis progression rate in HIV-infected patients with undetectable HIV viral load (VL. For this reason, we performed the present study. Materials and Methods: Observational and multicenter study (2008–2012 conducted in four hospitals of the northern Spain. HIV/HCV (hepatitis c virus coinfected patients ≥18 years on stable combination antiretroviral therapy (cART (≥6 months and with a HIV VL <50 copies/mL were selected to analyze their liver fibrosis progression. Fibrosis progression was assessed using a Fibroscan® (502 STEP 3 model and measuring a basal test and a second one at least 12 months apart from baseline. This evolution was compared with different variables such as duration of HIV/HCV coinfection, gender, age, previous treatment for HCV, HCV genotype, CD4 lymphocyte counts and the cART employed at the basal test. Results: A total of 608 patients were included (median age 29.4 years, 71.7% men. Of these, 463 patients met the inclusion criteria. In these patients, the liver fibrosis progression was nearly flat and the only variables related to a higher liver fibrosis progression were the increasing age of the patients (p=0.02 and the duration of the coinfection (p=0.001. CD4 lymphocyte counts showed a tendency to improved liver fibrosis (p=0.056. Conclusions: In HIV/HCV coinfected patients on stable cART and HIV undetectable VL, the increase in liver fibrosis rate progression was nearly flat, although it was significantly associated with the duration of the coinfection and the age of the patient. The beneficial effects of the cART were independent of the antiretroviral drug employed. A tendency to a lower fibrosis progression was observed in those patients with a higher CD4 count.

  17. Prevalence of HIV, Hepatitis B and C Infections and an Assessment of HCV-Genotypes and Two IL28B SNPs among People Who Inject Drugs in Three Regions of Nepal

    Science.gov (United States)

    Kinkel, Hans-Tilmann; Karmacharya, Dibesh; Shakya, Jivan; Manandhar, Sulochana; Panthi, Santosh; Karmacharya, Prajwola; Sitaula, Deepika; Thapaliya, Reenu; K. C., Prawachan; Rai, Apurva; Dixit, Sameer

    2015-01-01

    As part of a comprehensive health care programme for people who use drugs in Nepal, HIV and viral hepatitis B and C status—including risk factors, HCV-genotypes and co-infections—as well as two IL28B Single-nucleotide polymorphisms (SNPs) were assessed for a random sample of 401 people who inject drugs in three regions of Nepal: mid-western Terrai (Nepalgunj), the eastern region (Dharan, Biratnagar) and the central region (Kathmandu, Lalitpur and Chitwan). Individuals were included who showed at least a minimum of health care seeking behaviour. This latter criterion was defined by being registered with any organisation offering health services. The average age of the participants was 30.5 yrs, and the average length of intravenous drug use was 8.5 yrs. The prevalence rates of HBsAg, anti-HIV antibodies and HCV-RNA were 3.5%, 13.8% and 41.9%, respectively. Spontaneous HCV clearance was evident in 16% of all of those who tested positive for anti-HCV antibodies. Independent risk factors for HCV-RNA positivity were age, gender, geographical region, duration of injecting drug use, history of imprisonment and HIV co-infection. In the age group ≤24 yrs, the rate of spontaneous HCV clearance was 43.5%. Overall, 59.8% of HCV infections were caused by HCV genotype 3 and 40.2% by HCV genotype 1. No other HCV genotypes were identified in this study. The IL28B SNP rs12979860 and rs8099917 were identified in 122 patients, and 75.4% of all participants had both favourable genotypes rs12979860 C/C and rs8099917 T/T. PMID:26263394

  18. EFFECT OF HIV PREVENTION AND TREATMENT PROGRAM ON HIV AND HCV TRANSMISSION AND HIV MORTALITY AT AN INDONESIAN NARCOTIC PRISON.

    Science.gov (United States)

    Nelwan, Erni J; Indrati, Agnes K; Isa, Ahmad; Triani, Nurlita; Alam, Nisaa Nur; Herlan, Maria S; Husen, Wahid; Pohan, Herdiman T; Alisjahbana, Bachti; Meheus, Andre; Van Crevel, Reinout; van der Ven, Andre Jam

    2015-09-01

    Validated data regarding HIV-transmission in prisons in developing countries is scarce. We examined sexual and injecting drug use behavior and HIV and HCV transmission in an Indonesian narcotic prison during the implementation of an HIV prevention and treatment program during 2004-2007 when the Banceuy Narcotic Prison in Indonesia conducted an HIV transmission prevention program to provide 1) HIV education, 2) voluntary HIV testing and counseling, 3) condom supply, 4) prevention of rape and sexual violence, 5) antiretroviral treatment for HIV-positive prisoners and 6) methadone maintenance treatment. During a first survey that was conducted between 2007 and 2009, new prisoners entered Banceuy Narcotics Prison were voluntary tested for HIV and HCV-infection after written informed consent was obtained. Information regarding sexual and injecting risk behavior and physical status were also recorded at admission to the prison. Participants who tested negative for both HIV and HCV during the first survey were included in a second survey conducted during 2008-2011. During both surveys, data on mortality among HIV-seropositive patients were also recorded. All HIV-seropositive participants receive treatment for HIV. HIV/ AIDS-related deaths decreased: 43% in 2006, 18% in 2007, 9% in 2008 and 0% in 2009. No HIV and HCV seroconversion inside Banceuy Narcotic Prison were found after a median of 23 months imprisonment (maximum follow-up: 38 months). Total of 484.8 person-years observation was done. Participants reported HIV transmission risk-behavior in Banceuy Prison during the second survey was low. After implementation of HIV prevention and treatment program, no new HIV or HCV cases were detected and HIV-related mortality decreased. PMID:26863859

  19. Systemic Cytokine and Interferon Responsiveness Patterns in HIV and HCV Mono and Co-Infections

    OpenAIRE

    Fernandez-Botran, Rafael; Joshi-Barve, Swati; Ghare, Smita; Barve, Shirish; Young, Mary; Plankey, Michael; Bordon, Jose

    2014-01-01

    The role of host response-related factors in the fast progression of liver disease in individuals co-infected with HIV and HCV viruses remains poorly understood. This study compared patterns of cytokines, caspase-1 activation, endotoxin exposure in plasma as well as interferon signaling in peripheral blood mononuclear cells from HIV/HCV co-infected (HIV+/HCV+), HCV mono-infected (HIV−/HCV+), HIV mono-infected (HIV+/HCV−) female patients and HIV- and HCV-uninfected women (HIV−/HCV−) who had en...

  20. Characteristics of co-infections by HCV and HBV among Brazilian patients infected by HIV-1 and/or HTLV-1

    Directory of Open Access Journals (Sweden)

    Marcia Moreira

    2013-12-01

    Full Text Available BACKGROUND: The human retroviruses HIV-1 and HTLV-1 share the routes of infection with hepatitis viruses B and C. Co-infection by these agents are a common event, but we have scarce knowledge on co-infection by two or more of these agents. OBJECTIVE: To evaluate the characteristics and risk factors for co-infections by HBV and HCV in patients infected by HIV-1 or/and HTLV-1, in Salvador, Brazil. METHODS: In a case-control study we evaluated patients followed in the AIDS and HTLV clinics of Federal University of Bahia Hospital. Clinical and epidemiological characteristics were reviewed, and patients were tested for the presence of serological markers of HBV and HCV infections. HCV-infected patients were tested by PCR to evaluate the presence of viremia. RESULTS: A total of 200 HIV-1, 213 HTLV-1-infected, and 38 HIV-HTLV-co-infected individuals were included. HIV-infected patients were more likely to have had more sexual partners in the lifetime than other patients' groups. HIV-HTLV-co-infected subjects were predominantly male. Patients infected by HTLV or co-infected had a significantly higher frequency of previous syphilis or gonorrhea, while HIV infection was mainly associated with HPV infection. Co-infection was significantly associated to intravenous drug use (IVDU. HBV and/or HCV markers were more frequently found among co-infected patients. HBV markers were more frequently detected among HIV-infected patients, while HCV was clearly associated with IVDU across all groups. AgHBs was strongly associated with co-infection by HIV-HTLV (OR = 22.03, 95% CI: 2.69-469.7, as well as confirmed HCV infection (p = 0.001. Concomitant HCV and HBV infection was also associated with retroviral co-infection. Patients infected by HTLV-1 had a lower chance of detectable HCV viremia (OR = 0.04, 95% CI: 0.002-0.85. CONCLUSIONS: Infection by HCV and/or HBV is frequent among patients presenting retroviral infection, but risk factors and prevalence for each

  1. Role of HCV Core gene of genotype 1a and 3a and host gene Cox-2 in HCV-induced pathogenesis

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    Ahmad Waqar

    2011-04-01

    Full Text Available Abstract Background Hepatitis C virus (HCV Core protein is thought to trigger activation of multiple signaling pathways and play a significant role in the alteration of cellular gene expression responsible for HCV pathogenesis leading to hepatocellular carcinoma (HCC. However, the exact molecular mechanism of HCV genome specific pathogenesis remains unclear. We examined the in vitro effects of HCV Core protein of HCV genotype 3a and 1a on the cellular genes involved in oxidative stress and angiogenesis. We also studied the ability of HCV Core and Cox-2 siRNA either alone or in combination to inhibit viral replication and cell proliferation in HCV serum infected Huh-7 cells. Results Over expression of Core gene of HCV 3a genotype showed stronger effect in regulating RNA and protein levels of Cox-2, iNOS, VEGF, p-Akt as compared to HCV-1a Core in hepatocellular carcinoma cell line Huh-7 accompanied by enhanced PGE2 release and cell proliferation. We also observed higher expression levels of above genes in HCV 3a patient's blood and biopsy samples. Interestingly, the Core and Cox-2-specific siRNAs down regulated the Core 3a-enhanced expression of Cox-2, iNOS, VEGF, p-Akt. Furthermore, the combined siRNA treatment also showed a dramatic reduction in viral titer and expression of these genes in HCV serum-infected Huh-7 cells. Taken together, these results demonstrated a differential response by HCV 3a genotype in HCV-induced pathogenesis, which may be due to Core and host factor Cox-2 individually or in combination. Conclusions Collectively, these studies not only suggest a genotype-specific interaction between key players of HCV pathogenesis but also may represent combined viral and host gene silencing as a potential therapeutic strategy.

  2. 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)

    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)

  3. [Consequences of extrahepatic manifestations of hepatitis C viral infection (HCV)].

    Science.gov (United States)

    Pawełczyk, Agnieszka

    2016-01-01

    The hepatitis C virus (HCV) is a primarily hepatotropic virus. However, numerous extrahepatic symptoms are observed in patients chronically infected with HCV, e.g. cryoglobulinemia, lymphoproliferative disorders, kidney diseases, disturbances of the central and peripheral nervous system, thyroid gland, pancreas, lymph nodes and pituitary gland, that develop at various times after the infection. Complex mechanisms underlie these processes, both molecular, related to direct effects of the virus on cells or tissues and indirect mechanisms, resulting from the response of the immune system to infection (via cytokines or oxidative stress), and from the antiviral treatment used. Understanding these mechanisms may contribute to the definition of new prognostic factors, important for the early diagnosis of the infection, which in turn may improve treatment efficacy. This paper is a review of the incidence of selected extrahepatic manifestations of HCV infection and their underlying pathogenetic mechanisms and risk factors. PMID:27117111

  4. Variation of transaminases, HCV-RNA levels and Th1/Th2 cytokine production during the post-partum period in pregnant women with chronic hepatitis C.

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    Angeles Ruiz-Extremera

    Full Text Available This study analyses the evolution of liver disease in women with chronic hepatitis C during the third trimester of pregnancy and the post-partum period, as a natural model of immune modulation and reconstitution. Of the 122 mothers recruited to this study, 89 were HCV-RNA+ve/HIV-ve and 33 were HCV-RNA-ve/HIV-ve/HCVantibody+ve and all were tested during the third trimester of pregnancy, at delivery and post-delivery. The HCV-RNA+ve mothers were categorized as either Type-A (66%, with an increase in ALT levels in the post-partum period (>40 U/L; P<0.001 or as Type-B (34%, with no variation in ALT values. The Type-A mothers also presented a significant decrease in serum HCV-RNA levels in the post-delivery period (P<0.001 and this event was concomitant with an increase in Th1 cytokine levels (INFγ, P = 0.04; IL12, P = 0.01 and IL2, P = 0.01. On the other hand, the Type-B mothers and the HCV-RNA-ve women presented no variations in either of these parameters. However, they did present higher Th1 cytokine levels in the partum period (INFγ and IL2, P<0.05 than both the Type-A and the HCV-RNA-ve women. Cytokine levels at the moment of delivery do not constitute a risk factor associated with HCV vertical transmission. It is concluded that differences in the ALT and HCV-RNA values observed in HCV-RNA+ve women in the postpartum period might be due to different ratios of Th1 cytokine production. In the Type-B women, the high partum levels of Th1 cytokines and the absence of post-partum variation in ALT and HCV-RNA levels may be related to permanent Th1 cytokine stimulation.

  5. The Cedar Project: high incidence of HCV infections in a longitudinal study of young Aboriginal people who use drugs in two Canadian cities

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    Spittal Patricia M

    2012-08-01

    Full Text Available Abstract Background Factors associated with HCV incidence among young Aboriginal people in Canada are still not well understood. We sought to estimate time to HCV infection and the relative hazard of risk factors associated HCV infection among young Aboriginal people who use injection drugs in two Canadian cities. Methods The Cedar Project is a prospective cohort study involving young Aboriginal people in Vancouver and Prince George, British Columbia, who use illicit drugs. Participants’ venous blood samples were drawn and tested for HCV antibodies. Analysis was restricted to participants who use used injection drugs at enrolment or any of follow up visit. Cox proportional hazards regression was used to identify independent predictors of time to HCV seroconversion. Results In total, 45 out of 148 participants seroconverted over the study period. Incidence of HCV infection was 26.3 per 100 person-years (95% Confidence Interval [CI]: 16.3, 46.1 among participants who reported using injection drugs for two years or less, 14.4 per 100 person-years (95% CI: 7.7, 28.9 among participants who had been using injection drugs for between two and five years, and 5.1 per 100 person-years (95% CI: 2.6,10.9 among participants who had been using injection drugs for over five years. Independent associations with HCV seroconversion were involvement in sex work in the last six months (Adjusted Hazard Ratio (AHR: 1.59; 95% CI: 1.05, 2.42 compared to no involvement, having been using injection drugs for less than two years (AHR: 4.14; 95% CI: 1.91, 8.94 and for between two and five years (AHR: 2.12; 95%CI: 0.94, 4.77 compared to over five years, daily cocaine injection in the last six months (AHR: 2.47; 95% CI: 1.51, 4.05 compared to less than daily, and sharing intravenous needles in the last six months (AHR: 2.56; 95% CI: 1.47, 4.49 compared to not sharing. Conclusions This study contributes to the limited body of research addressing HCV infection among

  6. Evaluation of Risk Factors of HCV infection in Lahore, (Pakistan

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    Rao Muhammad Ijaz

    2007-01-01

    Full Text Available Hepatitis C Virus (HCV infection is rapidly growing disease in world in general and in Pakistan in particular. In Pakistan more than 10 million persons have HCV +ve signs. Risk factors for this fatal disease included main, historic and demographic factors. Some researchers segregated few independent factors but other, include them in the category of depends. We have collected the data for Lahore (Pakistan and analyzed this data by considering the aforesaid factors. Some results of this research do not match with the existing theories. We recommended that interaction effects of associated factors should also be considered in evaluation.

  7. HCV Animal Models: A Journey of More than 30 Years

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    Philip Meuleman

    2009-09-01

    Full Text Available In the 1970s and 1980s it became increasingly clear that blood transfusions could induce a form of chronic hepatitis that could not be ascribed to any of the viruses known to cause liver inflammation. In 1989, the hepatitis C virus (HCV was discovered and found to be the major causative agent of these infections. Because of its narrow ropism, the in vivo study of this virus was, especially in the early days, limited to the chimpanzee. In the past decade, several alternative animal models have been created. In this review we review these novel animal models and their contribution to our current understanding of the biology of HCV.

  8. HCV animal models: a journey of more than 30 years.

    Science.gov (United States)

    Meuleman, Philip; Leroux-Roels, Geert

    2009-09-01

    In the 1970s and 1980s it became increasingly clear that blood transfusions could induce a form of chronic hepatitis that could not be ascribed to any of the viruses known to cause liver inflammation. In 1989, the hepatitis C virus (HCV) was discovered and found to be the major causative agent of these infections. Because of its narrow tropism, the in vivo study of this virus was, especially in the early days, limited to the chimpanzee. In the past decade, several alternative animal models have been created. In this review we review these novel animal models and their contribution to our current understanding of the biology of HCV. PMID:21994547

  9. Angiogenic output in viral hepatitis, C and B, and HCV-associated hepatocellular carcinoma

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    Mohamed A. Abdel Mohsen

    2014-09-01

    Conclusion: The increased hepatic angiogenesis in chronic HCV and HBV could provide the molecular basis for liver carcinogenesis and contribute to the increased risk of HCC in patients with cirrhosis due to HCV and/or HBV.

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

    OpenAIRE

    Chris R. Kenyon; Robert Colebunders

    2014-01-01

    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 individ...

  11. Systemic cytokine and interferon responsiveness Patterns in HIV and HCV mono and co-infections.

    Science.gov (United States)

    Fernandez-Botran, Rafael; Joshi-Barve, Swati; Ghare, Smita; Barve, Shirish; Young, Mary; Plankey, Michael; Bordon, Jose

    2014-11-01

    The role of host response-related factors in the fast progression of liver disease in individuals co-infected with HIV and HCV viruses remains poorly understood. This study compared patterns of cytokines, caspase-1 activation, endotoxin exposure in plasma as well as interferon signaling in peripheral blood mononuclear cells from HIV/HCV co-infected (HIV(+)/HCV(+)), HCV mono-infected (HIV(-)/HCV(+)), HIV mono-infected (HIV(+)/HCV(-)) female patients and HIV- and HCV-uninfected women (HIV(-)/HCV(-)) who had enrolled in the Women's Interagency HIV Study (WIHS). HIV(+)/HCV(+) women had higher plasma levels of pro-inflammatory cytokines as well as caspase-1 compared with other groups. Both HIV(+)/HCV(+) and HIV(+)/HCV(-) women had significantly higher sCD14 levels compared with other groups. Peripheral blood mononuclear cells from HCV mono-infected patients had reduced levels of phosphorylation of STAT1 compared with other groups as well as lower basal levels of expression of the IFN-stimulated genes, OAS1, ISG15, and USP18 (UBP43). Basal expression of USP18, a functional antagonist of ISG15, as well as USP18/ISG15 ratios were increased in the HIV(+)/HCV(+) group compared with HIV(-)/HCV(+) and HIV(+)/HCV(-) groups. A more pronounced systemic inflammatory profile as well as increased expression ratios of USP18 to ISG15 may contribute to the more rapid progression of liver disease in HIV(+)/HCV(+) individuals. PMID:24955730

  12. Ways and intensity of vertical transfer of the HCV from infected mothers to children

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    Idelbay Shuratov

    2011-03-01

    Full Text Available Ways and intensity of vertical transfer HCV have been studied before sorts in 29 lying-in women, positive on HCV-RNA. Among newborns from these mothers in serum of blood of umbilical cord at the moment of birth, HCV-RNA is found in 6.8%. The infection of newborns from HCV-RNA positive mother occurs through a placenta and at the time of delivery.

  13. Validity of Autotaxin as a Novel Diagnostic Marker for Liver Fibrosis in Egyptian Chronic HCV Patients

    OpenAIRE

    Ezzat, Wafaa M.; Halla M. Ragab; Nabila Abd El Maksoud; Nour A. Abdulla; Yasser A. Elhosary

    2013-01-01

    We aimed to detect the validity of serum ATX as a diagnostic marker for liver fibrosis. Forty-eight males and 16 females were enrolled in the current study. Their ages ranged from 29-57 years with mean of 45.09, all were chronically HCV infected. Laboratory assessment was done for all subjects in form of complete blood picture; liver function test; lipid profile and serum detection of ATX. Patients were grouped according to the stage of fibrosis into group 1: fibrosis score 0, 1, 2, 3; group ...

  14. Effect of route of delivery on heterologous protection against HCV induced by an adenovirus vector carrying HCV structural genes

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    Guan Jie

    2011-11-01

    Full Text Available Abstract Background An effective vaccine and new therapeutic methods for hepatitis C virus (HCV are needed, and a potent HCV vaccine must induce robust and sustained cellular-mediated immunity (CMI. Research has indicated that adenoviral and vaccinia vectors may have the ability to elicit strong B and T cell immune responses to target antigens. Results A recombinant replication-defective adenovirus serotype 5 (rAd5 vector, rAd5-CE1E2, and a recombinant Tian Tan vaccinia vector, rTTV-CE1E2, were constructed to express the HCV CE1E2 gene (1-746 amino acid HCV 1b subtype. Mice were prime-immunised with rAd5-CE1E2 delivered via intramuscular injection (i.m., intranasal injection (i.n., or intradermal injection (i.d. and boosted using a different combination of injection routes. CMI was evaluated via IFN-γ ELISPOT and ICS 2 weeks after immunisation, or 16 weeks after boost for long-term responses. The humoral response was analysed by ELISA. With the exception of priming by i.n. injection, a robust CMI response against multiple HCV antigens (core, E1, E2 was elicited and remained at a high level for a long period (16 weeks post-vaccination in mice. However, i.n. priming elicited the highest anti-core antibody levels. Priming with i.d. rAd5-CE1E2 and boosting with i.d. rTTV-CE1E2 carried out simultaneously enhanced CMI and the humoral immune response, compared to the homologous rAd5-CE1E2 immune groups. All regimens demonstrated equivalent cross-protective potency in a heterologous surrogate challenge assay based on a recombinant HCV (JFH1, 2a vaccinia virus. Conclusions Our data suggest that a rAd5-CE1E2-based HCV vaccine would be capable of eliciting an effective immune response and cross-protection. These findings have important implications for the development of T cell-based HCV vaccine candidates.

  15. Strategies to manage hepatitis C virus (HCV) disease burden

    DEFF Research Database (Denmark)

    Wedemeyer, H; Duberg, A S; Buti, M;

    2014-01-01

    The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and...

  16. Endothelial dysfunction correlates with liver fibrosis in chronic HCV infection.

    Science.gov (United States)

    Barone, Michele; Viggiani, Maria Teresa; Amoruso, Annabianca; Schiraldi, Serafina; Zito, Annapaola; Devito, Fiorella; Cortese, Francesca; Gesualdo, Michele; Brunetti, Natale; Di Leo, Alfredo; Scicchitano, Pietro; Ciccone, Marco Matteo

    2015-01-01

    Background. Hepatitis C virus (HCV) infection can exert proatherogenic activities due to its direct action on vessel walls and/or via the chronic inflammatory process involving the liver. Aims. To clarify the role of HCV in atherosclerosis development in monoinfected HCV patients at different degrees of liver fibrosis and with no risk factors for coronary artery disease. Methods. Forty-five patients were included. Clinical, serological, and anthropometric parameters, liver fibrosis (transient liver elastometry (fibroscan) and aspartate aminotransferase to platelet ratio index (APRI)), carotid intima-media thickness (c-IMT), and brachial artery flow-mediated vasodilatation (FMD) were assessed. Patients were divided into 3 tertiles according to fibroscan values. Results. Patients in the third tertile (fibroscan value >11.5 KPa) showed FMD values were significantly lower than second and first tertiles (4.7 ± 1.7% versus 7.1 ± 2.8%, p = 0.03). FMD values were inversely related to liver elastomeric values. c-IMT values were normal. The risk for endothelial dysfunction development in the third tertile (p = 0.02) was 6.9 higher than the first tertile. A fibroscan value >11.5 KPa had a positive predictive power equal to 79% for endothelial dysfunction. Conclusions. HCV advanced liver fibrosis promotes atherosclerosis by inducing endothelial dysfunction independently of common cardiovascular risk factors. PMID:26000012

  17. Hepatitis C testing: interpretation, implications, and counseling.

    Science.gov (United States)

    Becherer, P R; Bacon, B

    1993-01-01

    New molecular biology techniques recently identified hepatitis C virus (HCV) as the major cause of non-A, non-B hepatitis. Serologic assays for HCV specific antibodies are a significant advance, but they require cautious interpretation due to problems with the tests' sensitivity and specificity. Patients with suspected HCV infection should be thoroughly evaluated to verify the presence of infection, to exclude other forms of chronic liver disease, and to determine the extent of liver damage prior to considering treatment. PMID:8421452

  18. Evaluation of the Procleix Ultrio Plus ID NAT assay for detection of HIV 1, HBV and HCV in blood donors

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    Raj Nath Makroo

    2015-01-01

    Full Text Available Introduction: The Procleix Ultrio Plusassay is a new-generation qualitative in vitro nucleic acid amplification test used to screen for human immunodeficiency virus type 1 (HIV-1 RNA, hepatitis C virus (HCV RNA and hepatitis B virus (HBV DNA in blood donors. This study was performed to compare the Procleix Ultrio assay with the new-generation Procleix Ultrio Plus Nucleic Acid Test (NAT assays. Materials and Methods: Ten thousand three hundred and two donor samples were run in parallel for ID NAT using the Procleix Ultrio and the Procleix Ultrio Plus assay. Simultaneously, enzyme-linked immunosorbent assay testing was performed on an EVOLIS Walk away System for HIV, HCV, HBsAg and anti-HBc. Reactive samples were confirmed using polymerase chain reaction. Results: In the 10,302 samples tested during the study period, we identified 15 NAT yields, and all these revealed HBV DNA in the discriminatory assays. Eight of these were exclusive yields from the Ultrio Plus assay and the remaining seven cases were determined as HBV NAT yield, both by the Procleix Ultrio as well as the Ultrio Plus assays, i.e. "Combined" yields. No HCV or HIV 1 yields were detected during the study period by either of two assays. Conclusion: With an overall yield rate of 1 in 687 and an exclusive yield rate of 1 in 1287, the Procleix Ultrio Plus assay proved to be highly sensitive in detecting occult HBV infections.

  19. 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.

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    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.

  20. Effects of HCV on Basal and Tat-Induced HIV LTR Activation

    OpenAIRE

    Sengupta, Satarupa; Powell, Eleanor; Kong, Ling; Blackard, Jason T.

    2013-01-01

    Hepatitis C virus (HCV) co-infection occurs in ∼30–40% of the HIV-infected population in the US. While a significant body of research suggests an adverse effect of HIV on HCV replication and disease progression, the impact of HCV on HIV infection has not been well studied. Increasing data suggest that hepatocytes and other liver cell populations can serve as reservoirs for HIV replication. Therefore, to gain insight into the impact of HCV on HIV, the effects of the HCV Core protein and infect...

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

    OpenAIRE

    Fahimeh Bagheri Amiri; Ehsan Mostafavi; Ali Mirzazadeh

    2016-01-01

    Background 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. Method Following PRISMA guidelines, we conducted a systematic review and meta-analysis of reports on prevalence of HIV, HBV, HCV and H...

  2. Performance and diagnostic usefulness of commercially available enzyme linked immunosorbent assay and rapid kits for detection of HIV, HBV and HCV in India

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    Maity Susmita

    2012-11-01

    Full Text Available Abstract Background HIV, HBV and HCV pose a major public health problem throughout the world. Detection of infection markers for these agents is a major challenge for testing laboratories in a resource poor setting. As blood transfusion is an important activity saving millions of live every year, it also carries a risk of transfusion transmissible infections caused by these fatal blood borne pathogens if the quality of testing is compromised. Conventional ELISA is regarded as the mostly used screening technique but due to limitations like high cost, unavailability in many blood banks and testing sites, involvement of costly instruments, time taking nature and requirement of highly skilled personnel for interpretation, rapid tests are gaining more importance and warrants comparison of performance. Results A comparative study between these two techniques has been performed using commercially available diagnostic kits to assess their efficacy for detection of HIV, HBV and HCV infections. Rapid kits were more efficient in specificity with synthetic antigens along with high PPV than ELISA in most cases. Comparison between different ELISA kits revealed that Microlisa HIV and Hepalisa (J. Mitra & Co. Pvt. Ltd.; ERBA LISA HIV1 + 2, ERBA LISA Hepatitis B and ERBA LISA HCV (Transasia Bio-medicals Ltd. gives uniform result with good performance in terms of sensitivity, specificity, PPV, NPV and efficiency, whereas, Microlisa HCV (J. Mitra & Co. Pvt. Ltd., Microscreen HBsAg ELISA and INNOVA HCV (Span Diagnostics Ltd. did not perform well. Rapid kits were also having high degree of sensitivity and specificity (100% except in HIV Comb and HCV Comb (J. Mitra & Co. Pvt. Ltd.. The kit efficiency didn’t vary significantly among different companies and lots in all the cases except for HCV ELISA showing statistically significant variation (p  Conclusions ELISA is a good screening assay for markers of HIV, HBV and HCV infections. Rapid tests are useful for

  3. Pharmacogenetics of efficacy and safety of HCV treatment in HCV-HIV coinfected patients: significant associations with IL28B and SOCS3 gene variants.

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    Francesc Vidal

    Full Text Available BACKGROUND AND AIMS: This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFNα 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected patients. METHODS: The study groups were made of 99 patients (efficacy pharmacogenetic substudy and of 114 patients (safety pharmacogenetic substudy. Polymorphisms in the following candidate genes IL28B, IL6, IL10, TNFα, IFNγ, CCL5, MxA, OAS1, SOCS3, CTLA4 and ITPA were assessed. Genotyping was carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain reaction. Efficacy end-points assessed were: rapid, early and sustained virological response (RVR, EVR and SVR, respectively. Safety end-points assessed were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal disturbances and depression. Chi square test, Student's T test, Mann-Whitney U test and logistic regression were used for statistic analyses. RESULTS: As efficacy is concerned, IL28B and CTLA4 gene polymorphisms were associated with RVR (p<0.05 for both comparisons. Nevertheless, only polymorphism in the IL28B gene was associated with SVR (p = 0.004. In the multivariate analysis, the only gene independently associated with SVR was IL28B (OR 2.61, 95%CI 1.2-5.6, p = 0.01. With respect to safety, there were no significant associations between flu-like syndrome or depression and the genetic variants studied. Gastrointestinal disturbances were associated with ITPA gene polymorphism (p = 0.04. Anemia was associated with OAS1 and CTLA4 gene polymorphisms (p = 0.049 and p = 0.045, respectively, neutropenia and thromobocytopenia were associated with SOCS3 gene polymorphism (p = 0.02 and p = 0.002, respectively. In the multivariate analysis, the associations of the SOCS3 gene polymorphism with neutropenia (OR 0.26, 95%CI 0

  4. Cell-death-inducing DFFA-like Effector B Contributes to the Assembly of Hepatitis C Virus (HCV) Particles and Interacts with HCV NS5A

    Science.gov (United States)

    Cai, Hua; Yao, Wenxia; Li, Leike; Li, Xinlei; Hu, Longbo; Mai, Runming; Peng, Tao

    2016-01-01

    Hepatitis C virus (HCV) uses components of the very-low-density lipoprotein (VLDL) pathway for assembly/release. We previously reported that hepatocyte nuclear factor 4α (HNF4α) participates in HCV assembly/release through downstream factors those participate in VLDL assembly/secretion. Cell-death-inducing DFFA-like effector B (CIDEB) is an important regulator of the VLDL pathway. CIDEB is required for entry of HCV particles from cell culture (HCVcc), but the effects of CIDEB on the post-entry steps of the HCV lifecycle are unclear. In the present study, we determined that CIDEB is required for HCV assembly in addition to HCVcc entry. Furthermore, CIDEB interacts with the HCV NS5A protein, and the N terminus of CIDEB and the domain I of NS5A are involved in this interaction. Moreover, CIDEB silencing impairs the association of apolipoprotein E (ApoE) with HCV particles. Interestingly, CIDEB is also required for the post-entry stages of the dengue virus (DENV) life cycle. Collectively, these results indicate that CIDEB is a new host factor that is involved in HCV assembly, presumably by interacting with viral protein, providing new insight into the exploitation of the VLDL regulator CIDEB by HCV. PMID:27282740

  5. HCV triple therapy in co-infection HIV/HCV is not associated with a different risk of developing major depressive disorder

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    Renata Fialho

    2014-11-01

    Full Text Available Introduction: Hepatitis C (HCV treatment options have changed with the development of direct activity antivirals (DAAs and the availability of triple therapies have improved HCV cure rates. A common neuropsychiatric side effect of pegylated-interferon and ribavirin treatment is major depressive disorder (MDD, however little is known about such adverse events with protease inhibitor-based triple therapy. The aim of this study was to assess the rate of MDD in co-infected HIV HCV patients undergoing different HCV treatments. Methods: All participants were co-infected HIV HCV attending the Royal Sussex County Hospital Brighton hepatology outpatient clinic between 2010 and 2014. Participants were assessed for DSM-IV MDD and depression severity (using the Hamilton depression scale (HAMD at baseline and monthly after treatment initiation. HIV and HCV stages, genotype, reinfection and standard demographic variables were recorded. Influence of HCV stage (acute vs. chronic and type of treatment (classic vs triple, emergence of MDD and clearance outcomes were analyzed using repeated measures and logistic regression models. Results: Fifty participants with a mean age of 42.65 years (SD=10.32 were included; most were male (98%. The majority had contracted HCV genotype 1 (64% or 4 (26%. The HCV stage and treatment groups were matched for age and depression at baseline. No significant differences were found on virological outcomes considering HCV stage and treatment. From baseline to SVR, there was a significant increase in HAMD scores, F(4,36=10.09, p<.001; this was not significantly influenced by HCV stage, F(4,35=0.54, p=.708 or HCV treatment group, F(4,35=0.60, p=.664. Those with chronic HCV were more likely to transition to MDD than acute infection (OR 7.77, 95% CI 2.04–29.54, p=.003. No differences were found for depression emergence by HCV treatment group (OR 0.83, 95% CI 0.22–3.13, p=.787. Conclusions: HCV triple therapy was not associated with a

  6. Intracellular expression of the proliferative marker Ki-67 and viral proteins (NS3, NS5A and C in chronic, long lasting hepatitis C virus (HCV infection.

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    Karolina Olejniczak

    2008-01-01

    Full Text Available Hepatitis C virus (HCV continues to represent the main causative agent of the hepatitis, which leads to chronic transformation of the process in 60-80% individuals. It remains unclear how far cellular expression of HCV proteins in vivo may represent an index of progression of the disease and of proliferative activity in the liver in chronic hepatitis C. Aim of the studies included detection and subcellular localization of three HCV proteins (NS3, NS5A and C in liver biopsies from adults (n=19 with chronic, long lasting hepatitis C as related to hepatocyte proliferative activity. The immunocytochemical ABC (avidin biotin-peroxidase complex technique was applied, alone or associated with the ImmunoMax technique. Results of the immunocytochemical tests were compared to histological alterations in liver biopsies, proliferation index and with selected clinical data. A significantly higher expression of NS3 protein was noted, as compared to expressions of NS5A and C proteins. In all the patients, cytoplasmic localization of all proteins dominated over nuclear localization (p0.05. At the level of electron microscopy, protein localization in endoplasmic reticulum (ER membranes, mitochondria, perinuclear region and/or in hepatocyte cell nucleus was observed. No direct relationships could be demonstrated between expressions of HCV proteins and of Ki-67 antigen. No correlations could also be demonstrated between cellular expression of any HCV protein on one hand and grading or staging, alanine transaminase (ALT, serum level of HCV RNA or alpha-fetoprotein (AFP on the other. However, positive correlations were disclosed between proliferative activity of hepatocytes on one hand and patient's age, grading and staging on the other. Advanced hepatic fibrosis correlated also with serum levels of AFP. The studies were supplemented with data on subcellular localization of HCV proteins. Moreover, they indicated that in HCV infection grading and staging

  7. Does diphenyl dimethyl bi carboxylate (DDB) cause healthy carrier state in HCV active patients

    International Nuclear Information System (INIS)

    The present study was conducted to investigate the possibility whether the DDB might induce an HCV healthy carrier state in HCV active patients. Blood samples were obtained from ten individuals with fulfilled criteria of HCV healthy carrier state; ten HCV active patients receiving no treatment, ten patients who completed 3 months course of DDB treatment and ten HCV active patients under DDB therapy. The following parameters were evaluated: the percentage of atypical lymphocytes and hyper segmented neutrophils in peripheral blood Leishmania stained film, albumin, C3 complement level, total IgM, immune complex and a-fetoprotein in serum. Prothrombin time and concentration were determined in citrated plasma. Data from the present study showed that the chronic active HCV patients experienced decreased serum albumin, atypical lymphocyte proportion, prolonged prothrombin time, increased hyper segmented neutrophils, serum total IgM and serum C3 and unchanged immune complex and a-fetoprotein when compared to those of HCV healthy carriers. DDB treatment only adjusted prothrombin time and concentration and serum C3 in HCV active patients to the HCV healthy carrier level. It had diverse or no effect on other parameters. In conclusion, DDB acts independently from causing an HCV healthy carrier state in HCV active patients

  8. Geographical variations of risk factors associated with HCV infection in drug users in southwestern China.

    Science.gov (United States)

    Zhou, Y B; Wang, Q X; Yang, M X; Gong, Y H; Yang, Y; Nie, S J; Liang, S; Nan, L; Coatsworth, A; Yang, A H; Liao, Q; Song, X X; Jiang, Q W

    2016-04-01

    Hepatitis C virus (HCV) has become a global public health problem. Many studies have been conducted to identify risk factors for HCV infection. However, some of these studies reported inconsistent results. Using data collected from 11 methadone clinics, we fit both a non-spatial logistical regression and a geographically weighted logistic regression to analyse the association between HCV infection and some factors at the individual level. This study enrolled 5401 patients with 30·0% HCV infection prevalence. The non-spatial logistical regression found that injection history, drug rehabilitation history and senior high-school education or above were related to HCV infection; and being married was negatively associated with HCV infection. Using the spatial model, we found that Yi ethnicity was negatively related to HCV infection in 62·0% of townships, and being married was negatively associated with HCV infection in 81·0% of townships. Senior high-school education or above was positively associated with HCV infection in 55·2% of townships of the Yi Autonomous Prefecture. The spatial model offers better understanding of the geographical variations of the risk factors associated with HCV infection. The geographical variations may be useful for customizing intervention strategies for local regions for more efficient allocation of limited resources to control transmission of HCV. PMID:26542331

  9. Clearance of low levels of HCV viremia in the absence of a strong adaptive immune response

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    Manns Michael P

    2007-06-01

    Full Text Available Abstract Spontaneous clearance of hepatitis C virus (HCV has frequently been associated with the presence of HCV-specific cellular immunity. However, there had been also reports in chimpanzees demonstrating clearance of HCV-viremia in the absence of significant levels of detectable HCV-specific cellular immune responses. We here report seven asymptomatic acute hepatitis C cases with peak HCV-RNA levels between 300 and 100.000 copies/ml who all cleared HCV-RNA spontaneously. Patients were identified by a systematic screening of 1176 consecutive new incoming offenders in a German young offender institution. Four of the seven patients never developed anti-HCV antibodies and had normal ALT levels throughout follow-up. Transient weak HCV-specific CD4+ T cell responses were detectable in five individuals which did not differ in strength and breadth from age- and sex-matched patients with chronic hepatitis C and long-term recovered patients. In contrast, HCV-specific MHC-class-I-tetramer-positive cells were found in 3 of 4 HLA-A2-positive patients. Thus, these cases highlight that clearance of low levels of HCV viremia is possible in the absence of a strong adaptive immune response which might explain the low seroconversion rate after occupational exposure to HCV.

  10. 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.

  11. Genotypes and viral load of hepatitis C virus among persons attending a voluntary counseling and testing center in Ethiopia.

    Science.gov (United States)

    Abreha, Tesfay; Woldeamanuel, Yimtubezinash; Pietsch, Corinna; Maier, Melanie; Asrat, Daniel; Abebe, Almaz; Hailegiorgis, Bereket; Aseffa, Abraham; Liebert, Uwe Gerd

    2011-05-01

    The prevalence of different genotypes of hepatitis C virus (HCV) in Ethiopia is not known. HCV genotypes influence the response to therapy with alpha-interferon alone or in combination with ribavirin. A cross sectional study was conducted on attendees of voluntary counseling and testing center. Serum samples from 1,954 (734 HIV positive and 1,220 HIV negative) individuals were screened for HCV antibody. Active HCV infection was confirmed by quantitative PCR in 18 of the 71 samples with anti-HCV antibodies. The HCV viral load ranged from 39,650 to 9,878,341 IU/ml (median 1,589,631 IU/ml) with no significant difference [χ(2)(17) = 18.00, P = 0.389] between persons positive or negative for HIV. The viral load of HCV was, however, higher in older study subjects (r = 0.80, P = 0.000). HCV genotypes were determined using the VERSANT HCV Genotype Assay (LiPA) and sequence analysis of the NS5b region of the HCV genome. Diverse HCV genotypes were found including genotypes 1, 2, 4, and 5. There was no difference in the distribution regarding the HIV status. As in other parts of the world, genotyping of HCV must be considered whenever HCV is incriminated as a cause of hepatitis. PMID:21351106

  12. Impact of Helicobacter pylori eradication on refractory thrombocytopenia in patients with chronic HCV awaiting antiviral therapy.

    Science.gov (United States)

    Hanafy, A S; El Hawary, A T; Hamed, E F; Hassaneen, A M

    2016-07-01

    The possibility of delaying treatment of HCV due to severe thrombocytopenia is challenging. This study aimed to detect the prevalence of active helicobacter infection as a claimed cause of thrombocytopenia in a cohort of Egyptian patients with chronic active HCV awaiting combined anti-viral therapy. The study included 400 chronic HCV patients with thrombocytopenia. Laboratory investigations included liver function tests, real time quantitative PCR, reticulocytic count, ESR, ANA, bone marrow aspiration, measurement of anti-helicobacter antibodies, and helicobacter stool antigen. Positive cases for active H. pylori were given the standard triple therapy for 2 weeks. Helicobacter stool antigen was detected 4 weeks after termination of therapy and the change in platelet count was detected 1 month after eradication. A total of 248 out of 281 seropositive patients for H. pylori (88.3 %) showed positive stool antigen (p = 0.01). Eradication was achieved in 169 (68.1 %) patients with platelet mean count 114.9 ± 18.8 × 10(3)/μl with highly significant statistical difference from pretreatment value (49.7 ± 9.2 × 10(3)/μl, p = 0.000). Seventy-nine patients were resistant to conventional triple therapy and given a 7-day course of moxifloxacin-based therapy; 61 patients responded (77.1 %) with mean platelet improvement from 76.4 ± 17.4 × 10(3)/μl to 104.2 ± 15.2 × 10(3)/μl (p = 0.000). The non-responders showed no improvement in their platelet count (74.6 ± 20.5 vs. 73.6 ± 15.3 × 10(3)/ul, P = 0.5). Eradication of active H. pylori in HCV augments platelet count and enhances the early start of antiviral therapy. PMID:27180243

  13. Usefulness of non-invasive serum markers for predicting liver fibrosis in Egyptian patients with chronic HCV infection.

    Science.gov (United States)

    El Guesiry, Dalal; Moez, Pacinte; Hossam, Nermine; Kassem, Mohamed

    2011-01-01

    Accurate monitoring of liver fibrosis changes in patients with hepatitis C virus (HCV) infection would be helpful in defining the need to intervene, implement the appropriate response in treatment and to minimize the use of liver biopsy. We aimed to evaluate the diagnostic utility of the different serum markers and indices in detecting liver fibrosis in study patients. Initial liver biopsy, routine liver function tests, estimation of hyaluronic acid, MMP-1, and PIIINP levels was performed for 30 Egyptian patients with HCV and 15 controls. Marker algorithms based on common laboratory such APRI score, Fibrotest and Actitest. PIIINP and MMP-1 serum markers were combined and entered into a stepwise logistic regression analysis with formulation of a score equation for fibrosis staging. Combined PIIINP and MMP-1 yielded different cut off scores to estimate two clinically relevant fibrosis stages: "significant fibrosis" versus "extensive fibrosis. Apri score also showed AUC of 1.0 with 100 % sensitivity and specificity to exclude the presence of cirrhosis and was significantly correlated to Metavair fibrosis stage in early fibrosis. On the other hand, PIIINP, Fibrotest and acti test were significantly correlated to Metavair fibrosis stage in both early and late fibrosis. In conclusion, integrating PIIINP/MMP-1 score was able to provide reliable information about the degree of liver fibrosis in chronic hepatitis C patients using different cut-offs values. A combination of liver markers as well as its related indices is an emerging tool to differentiate early from advanced liver fibrosis in HCV patients. PMID:23082465

  14. Managing HCV infection in pediatric age group: Suggested recommendations

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    Danish Fazal

    2010-01-01

    Full Text Available Hepatitis C virus (HCV infection in children is different from the adult infection in many ways, like natural course of the disease; duration, therapeutic response and side effects profile of the drug therapy; and prognosis. Special considerations include consideration on what could be the appropriate time to investigate a suspected child, when to institute drug therapy and how to prevent vertical transmission. Although over the past one decade many landmark studies have greatly increased our insight on this subject, yet we are far from developing a consensus statement. In this article, a concise yet comprehensive review of HCV infection in children - diagnosis and treatment - is given, followed by suggested recommendations at the end. It is hoped that these recommendations will help develop local guidelines on this subject.

  15. Review article: HCV – STAT-C era of therapy

    OpenAIRE

    Lange, Christian Markus; Sarrazin, Christoph; Zeuzem, Stefan

    2010-01-01

    Abstract Background: Numerous ?specifically targeted antiviral therapy for hepatitis C? (STAT-C) compounds are currently under development to improve treatment opportunities of chronic hepatitis C virus-(HCV)-infection. Aim: To review the potential of STAT-C agents which are currently under clinical development. Methods: Studies evaluating STAT-C compounds were identified by systematic literature search using PubMed and databases of abstracts presented in English at recent l...

  16. Prevalence of occult HBV infection in haemodialysis patients with chronic HCV

    Institute of Scientific and Technical Information of China (English)

    Vedat Goral; Hamza Ozkul; Selahattin Tekes; Dede Sit; Ali Kemal Kadiroglu

    2006-01-01

    AIM: To study the prevalence and clinical effects of occult HBV infection in haemodialysis patients with chronic HCV.METHODS: Fifty chronic hemodialysis patients with negative HbsAg, and positive anti-HCV were included in the study. These patients were divided into two groups:HCV-RNA positive and HCV-RNA negative, based on the results of HCV-RNA PCR. HBV-DNA was studied using the PCR method in both groups.RESULTS: None of the 22 HCV-RNA positive patients and 28 HCV-RNA negative patients revealed HBV-DNA in serum by PCR method. The average age was 47.2 ± 17.0 in the HCV-RNA positive group and 39.6 ± 15.6 in the HCV-RNA negative group.CONCLUSION: The prevalence of occult HBV infection is not high in haemodialysis patients with chronic HCV in our region. This result of our study has to be evaluated in consideration of the interaction between HBsAg positivity (8%-10%) and frequency of HBV mutants in our region.

  17. Genetic diversity of HCV among various high risk populations (IDAs, thalassemia, hemophilia, HD patients) in Iran

    Institute of Scientific and Technical Information of China (English)

    Rafiei A; Darzyani Azizi M; Taheri S; Haghshenas MR; Hosseinian A; Makhlough A

    2013-01-01

    Objective: To determine the patterns of distribution of HCV genotypes among high risk population in north of Iran. Methods: A cross-sectional study was conducted on 135 HCV RNA-positive high risk individuals including thalassemia, hemophilia, patients under hemodialysis and intravenous drug addicts. HCV genotypes were determined based on amplification with type-specific primers methods. Results: Among the 187 anti-HCV positive samples, only 135 (72.2%) gave HCV-RNA positvity. Over all, the most identified HCV type was genotype 3a (51.1%) followed by 1a (27.4%), 1b (8.2%). Sixteen (11.9%) out of 135 HCV RNA-positive participants have infected with more than one genotype or subtypes as follow; 1a/1b in 11 (8.2%), 2/3a in 3 (2.2%), and 1a/1b/3a in 2 (1.5%). Stratification of participants revealed that HCV subtype 3a was more prominent in thalassemia, hemophilia and HD patients but 1a and 1b were frequent in intravenous drug addicts. Conclusions: This study is the first report on HCV genotypes among Iranian subjects with different exposure categories resided in Mazandaran, where genotype 3a was found to be the most frequent genotype in thalassemia, hemophilia, and hemodialysis patients but not in IDAs. Since the addiction age is decreasing in Iran and a lot of addicts are IDAs, it might change the subtype pattern of HCV in general population.

  18. Rituximab-Based Treatment, HCV Replication, and Hepatic Flares

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    Evangelista Sagnelli

    2012-01-01

    Full Text Available Rituximab, a chimeric mouse-human monoclonal antibody directed to the CD20 antigen expressed on pre-B lymphocytes and mature lymphocytes, causes a profound B-cell depletion. Due to its peculiar characteristics, this drug has been used to treat oncohaematological diseases, B cell-related autoimmune diseases, rheumatoid arthritis, and, more recently, HCV-associated mixed cryoglobulinaemic vasculitis. Rituximab-based treatment, however, may induce an increased replication of several viruses such as hepatitis B virus, cytomegalovirus, varicella-zoster virus, echovirus, and parvovirus B19. Recent data suggest that rituximab-based chemotherapy induces an increase in HCV expression in hepatic cells, which may become a target for a cell-mediated immune reaction after the withdrawal of treatment and the restoration of the immune control. Only a few small studies have investigated the occurrence of HCV reactivation and an associated hepatic flare in patients with oncohaematological diseases receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. These studies suggest that the hepatic flares are frequently asymptomatic, but life-threatening liver failure occurs in nearly 10% of cases.

  19. Current therapeutic strategies for HCV-associated cryoglobulinemia

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    F. Iannuzzella

    2011-09-01

    Full Text Available Cryoglobulinemia refers to the presence in serum of immunoglobulins, that reversibly precipitate at low temperatures. Cryoglobulins are classified according to their immunochemical properties as type I, composed of a single monoclonal immunoglobulin, and types II and III, referred as mixed cryoglobulinemia (MC, composed by a mixture of monoclonal (type II and polyclonal (type III IgM that have rheumatoid factor activity and bind to polyclonal IgGs. MC is a systemic vasculitis with cutaneous and multiple organ involvement including chronic hepatitis, membrano-proliferative glomerulonephritis, and peripheral neuropathy. In more than 90% of patients, MC is associated with chronic hepatitis C virus (HCV infection, which is considered the triggering factor of the disease. Patients with HCV-related MC may be managed by means of etiological, pathogenetic or symptomatic therapeutic modalities. The choice of the more appropriate treatment is strictly related to the assessment of disease activity, and to the extent and severity of organ involvement. This paper reviews the currently available therapeutic strategies for MC syndrome, emphasizing the importance of HCV eradication, and the safety/efficacy of new biologic therapies for selective control of cryoglobulin-producing B-cells.

  20. Frequency of HBsAg, anti-HCV, and anti-HIV in pregnant women and/or patients with gynecologic diseases in a tertiary hospital

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    Tülay Özlü

    2013-06-01

    Full Text Available Objective: Hepatitis B virus (HBV, hepatitis C virus (HCV and human immunodeficiency virus (HIV are viruses that can be transmitted to the health care workers by infected body fluids and from mother to the baby before, during or after delivery. In the present study, we aimed to investigate the frequency of hepatitis B surface antigens (HBsAg, hepatitis C antibodies (anti-HCV, and HIV antibodies (anti-HIV in pregnant women and/or patients with gynecologic diseases that admit to a university hospital in Bolu.Methods: HBsAg, anti-HCV, and anti-HIV results of the pregnant women and/or patients with gynecologic diseases that admitted to the obstetrics and gynecology clinics between January 2006 and June 2012 were retrospectively investigated. All markers were tested in the microbiology laboratory of our hospital by using macro ELISA method (Axsyme and Architect i2000SR systems, Abbott Diagnostics, Chicago, IL, USA.Results: The frequency of HBsAg, anti-HCV, and antiHIV positivity were 1.8%, 0.5%, and 0% in pregnant women and 1.9%, 1.1%, and 0% in patients with gynecologic diseases, respectively.Conclusion: The frequencies detected in our hospital are at low levels as seen in developed countries. Since there is no effective method of prevention especially from HCV, awareness of this serologic result before high risk procedures will enable the doctors and the health care workers to take extensive measures to prevent the transmission of the disease. J Clin Exp Invest 2013; 4 (2: 166-170Key words: anti-HCV, anti-HIV, HBsAg, pregnant women, gynecology

  1. Seroprevalence of HIV, HBV, HCV and syphilis in blood donors in Southern Haryana.

    Science.gov (United States)

    Arora, Dimple; Arora, Bharti; Khetarpal, Anshul

    2010-01-01

    Blood transfusion is an important mode of transmission of infections to recipients. The aim of the study was to assess the prevalence of transfusion-transmissible infections among blood donors. For this, a 3.5-year retrospective study, from October 2002 to April 2006 was conducted at the blood transfusion centre of Maharaja Agrasen Medical College, Agroha (Hisar) Haryana. Donors were screened for seroprevalence of HIV, HBV, HCV and syphilis. A total of 5849 donors were tested, out of which 4010 (68.6%) were replacement donors and 1839 (31.4%) were voluntary donors. The seroprevalence of HIV was 0.3% in the donors. No voluntary donor was found to be positive for HIV. The low sero-positivity among donors is attributed to pre-donation counseling in donor selection. The seroprevalence of HBV, HCV and syphilis was 1.7%, 1.0% and 0.9% respectively in total donors. The seroprevalence of hepatitis and syphilis was more in replacement donors as compared to voluntary donors. PMID:20551540

  2. Chimeric hepatitis B virus (HBV)/hepatitis C virus (HCV) subviral envelope particles induce efficient anti-HCV antibody production in animals pre-immunized with HBV vaccine.

    Science.gov (United States)

    Beaumont, Elodie; Roingeard, Philippe

    2015-02-18

    The development of an effective, affordable prophylactic vaccine against hepatitis C virus (HCV) remains a medical priority. The recently described chimeric HBV-HCV subviral envelope particles could potentially be used for this purpose, as they could be produced by industrial procedures adapted from those established for the hepatitis B virus (HBV) vaccine. We show here, in an animal model, that pre-existing immunity acquired through HBV vaccination does not influence the immunogenicity of the HCV E2 protein presented by these chimeric particles. Thus, these chimeric HBV-HCV subviral envelope particles could potentially be used as a booster in individuals previously vaccinated against HBV, to induce protective immunity to HCV. PMID:25596457

  3. Liver Retransplantation for Recurrence of HCV-Related Cirrhosis Using Hepatitis C-Positive Allografts: A 19-Year OPTN Analysis.

    Science.gov (United States)

    Torosian, Justin C; Leiby, Benjamin E; Fenkel, Jonathan M; Frank, Adam M; Ramirez, Carlo G; Doria, Cataldo

    2016-01-01

    BACKGROUND Liver re-transplantation (re-OLT) in hepatitis C-infected (HCV+) recipients remains a controversial life-saving procedure, as the process of allograft HCV reinfection is universal. Current literature and practice show that in primary liver transplantations (OLT) in HCV+ recipients, HCV+ grafts have equivalent graft survival as non-infected (HCV-) grafts. MATERIAL AND METHODS Standard Transplant Analysis and Research (STAR) files from the OPTN (Organ Procurement and Transplantation Network) were used to identify HCV+ patients who underwent a second transplant between 3/16/1994 and 6/30/2013. Of 33 816 HCV+ patients who underwent primary OLT during this time 2345 underwent re-OLT; of whom 2079 could be confirmed as second transplants. Out of 2079 HCV+ patients who underwent retransplantation, 75 received HCV+ grafts and 2004 received HCV- grafts. Excluding primary or secondary graft losses within 1 week of transplant, 60 HCV+ donor grafts and 1557 HCV- donor grafts at re-transplantation remained for more focused analysis. RESULTS Graft survival for these patients appeared essentially identical regardless of whether they received an HCV+ or HCV- graft. In addition, using the 33 816 HCV+ patients who underwent primary transplantation during this time, our data agreed with the results of previous studies showing that HCV+ patients who receive HCV+ grafts at first transplant have equivalent graft and patient survival rates. CONCLUSIONS Due to the equivalency of HCV graft survival in re-OLT, selecting HCV+ donor organs for hepatitis C-infected recipients appears to be appropriate. PMID:27137953

  4. Detection of hepatitis C virus RNA in saliva samples from patients with seric anti-HCV antibodies

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    Patrícia L. Gonçalves

    2005-02-01

    Full Text Available We examined the frequency of HCV-RNA in saliva samples from anti-HCV positive patients. Both plasma and saliva samples from 39 HCV patients (13 with normal liver enzymes, 19 with abnormal liver enzymes and 13 with cirrhosis were investigated. Stimulated saliva and fresh plasma were centrifuged (900 x g,10 min and stored at -70ºC, after the addition of guanidine isothiocyanate RNA extraction buffer. HCV-RNA was detected by RT- nested-PCR (amplification of HCV-cDNA for two rounds, using HCV primers 939/209 and 940/211. HCV genotyping was carried out by RFLP (using Mva I and Hinf 1 or Hae III and Rsa I restriction enzymes. Thirty-two out of 39 (82%; 95% CI=70-94% anti-HCV-positive patients had HCV-RNA in plasma samples. Eight out of 39 (20.5%; 95% CI=6.6-34.4% had HCV-RNA in the saliva. The HCV genotype in saliva samples from these patients matched the genotype found for plasma HCV-RNA. No significant correlation between the presence of HCV and either age, gender, HCV genotype or any risk factor for HCV infection was found. The observed prevalence (20.5% of anti HCV positive patients or 25% of the patients with HCV-RNA in plasma was lower than that previously reported from other countries. The low frequency of HCV-RNA in saliva samples observed in our study may be due to the use of cell-free saliva. Other authors reporting higher frequencies of HCV-RNA in saliva used whole saliva, without centrifugation.

  5. Design and expression of fusion protein consists of HBsAg and Polyepitope of HCV as an HCV potential vaccine

    Science.gov (United States)

    Gholizadeh, Monireh; Khanahmad, Hossein; Memarnejadian, Arash; Aghasadeghi, Mohammad Reza; Roohvand, Farzin; Sadat, Seyed Mehdi; Cohan, Reza Ahangari; Nazemi, Ali; Motevalli, Fatemeh; Asgary, Vahid; Arezumand, Roghaye

    2015-01-01

    Background: Hepatitis C virus (HCV) infection is a serious public health threat worldwide. Cellular immune responses, especially cytotoxic T-lymphocytes (CTLs), play a critical role in immune response toward the HCV clearance. Since polytope vaccines have the ability to stimulate the cellular immunity, a recombinant fusion protein was developed in this study. Materials and Methods: The designed fusion protein is composed of hepatitis B surface antigen (HBsAg), as an immunocarrier, fused to an HCV polytope sequence. The polytope containing five immunogenic epitopes of HCV was designed to induce specific CTL responses. The construct was cloned into the pET-28a, and its expression was investigated in BL21 (DE3), BL21 pLysS, BL21 pLysE, and BL21 AI Escherichia coli strains using 12% gel sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Finally, the identity of expressed fusion protein was confirmed by Western blotting using anti-His monoclonal antibody and affinity chromatography was applied to purify the expressed protein. Results: The accuracy of the construct was confirmed by restriction map analysis and sequencing. The transformation of the construct into the BL21 (DE3), pLysS, and pLysE E. coli strains did not lead to any expression. The fusion protein was found to be toxic for E. coli DE3. By applying two steps inhibition, the fusion protein was successfully expressed in BL21 (AI) E. coli strain. Conclusion: The HBsAg-polytope fusion protein expressed in this study can be further evaluated for its immunogenicity in animal models. PMID:26682209

  6. Public health clinic-based hepatitis C testing and linkage to care in Baltimore.

    Science.gov (United States)

    Falade-Nwulia, O; Mehta, S H; Lasola, J; Latkin, C; Niculescu, A; O'Connor, C; Chaulk, P; Ghanem, K; Page, K R; Sulkowski, M S; Thomas, D L

    2016-05-01

    Testing and linkage to care are important determinants of hepatitis C virus (HCV) treatment effectiveness. Public health clinics serve populations at high risk of HCV. We investigated their potential to serve as sites for HCV testing, initiation of and linkage to HCV care. Cross-sectional study of patients accessing sexually transmitted infection (STI) care at the Baltimore City Health Department (BCHD) STI clinics, from June 2013 through April 2014 was conducted. Logistic regression was used to assess factors associated with HCV infection and specialist linkage to care. Between 24 June 2013 and 15 April 2014, 2681 patients were screened for HCV infection. Overall, 189 (7%) were anti-HCV positive, of whom 185 (98%) received follow-up HCV RNA testing, with 155 (84%) testing RNA positive. Of 155 RNA-positive individuals, 138 (89%) returned to the STI clinic for HCV RNA results and initial HCV care including counselling regarding transmission and harm reduction in alcohol, and 132 (85%) were referred to a specialist for HCV care. With provision of patient navigation services, 81 (52%) attended an offsite HCV specialist appointment. Alcohol use and lack of insurance coverage were associated with lower rates of specialist linkage (OR 0.4 [95% CI 0.1-0.9] and OR 0.4 [95% CI 0.1-0.9], respectively). We identified a high prevalence of HCV infection in BCHD STI clinics. With availability of patient navigation services, a large proportion of HCV-infected patients linked to off-site specialist care. PMID:26840570

  7. ORIGINAL ARTICLE: Blood Donor’s Status of HIV, HBV, HCV and Syphilis in this Region of Marathwada, India

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    Rangrao H. Deshpande

    2012-07-01

    Full Text Available Aims & Objectives: Blood transfusion can cause the transmission of infections to recipients. This is an important mode of infection. The aim of study was to assess the prevalence of such type of infections among blood donors and to compare the seroprevalence of transfusion transmitted diseases in voluntary donors and replacement donors. Retrospective study of five years from Jan. 2007 to Dec. 2011 was done. This study was conducted at Blood bank, MIMSR Medical College Latur, Govt. Medical College, Latur and Bhalchandra Blood bank, Latur. Material & Methods: Total 10, 4925 donors were tested. Donors were screened for seroprevalence of HIV, HBC, HCV and Syphilis. Screening of HIV, HBV & HCV was done by ELISA method & Syphilis was screened by RPR type. Results: The comparison of seroprevalence of HIV, HBV, HCV & Syphilis in voluntary donors and replacement donors showed significant difference only for HIV in the years 2007, 2010, and 2011. Conclusion: The seroprevalence of transfusion transmitted diseases in the study is very low or negligible in voluntary donors as compared to replacement donors. There was a declining trend of seroprevalence for all the disease screened. But in our study the difference is not significant, which indicates that the selection of donors is of low quality. The selection of high quality voluntary donors should be achieved by creation of awareness by education of the prospective donor populations.

  8. 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.

  9. Development of a Multiplex Real-Time PCR Assay for the Detection of Treponema pallidum, HCV, HIV-1, and HBV.

    Science.gov (United States)

    Zhou, Li; Gong, Rui; Lu, Xuan; Zhang, Yi; Tang, Jingfeng

    2015-01-01

    Treponema pallidum, hepatitis C virus (HCV), human immunodeficiency virus (HIV)-1, and hepatitis B virus (HBV) are major causes of sexually transmitted diseases passed through blood contact. The development of a sensitive and efficient method for detection is critical for early diagnosis and for large-scale screening of blood specimens in China. This study aims to establish an assay to detect these pathogens in clinical serum specimens. We established a TaqMan-locked nucleic acid (LNA) real-time polymerase chain reaction (PCR) assay for rapid, sensitive, specific, quantitative, and simultaneous detection and identification. The copy numbers of standards of these 4 pathogens were quantified. Standard curves were generated by determining the mean cycle threshold values versus 10-fold serial dilutions of standards over a range of 10(6) to 10(1) copies/μL, with the lowest detection limit of the assay being 10(1) copies/μL. The assay was applied to 328 clinical specimens and compared with enzyme-linked immunosorbent assay (ELISA) and commercial nucleic acid testing (NAT) methods. The assay identified 39 T. pallidum-, 96 HCV-, 13 HIV-1-, 123 HBV-, 5 HBV/HCV-, 1 T. pallidum/HBV-, 1 HIV-1/HCV-, and 1 HIV-1/T. pallidum-positive specimens. The high sensitivity of the assay confers strong potential for its use as a highly reliable, cost-effective, and useful molecular diagnostic tool for large-scale screening of clinical specimens. This assay will assist in the study of the pathogenesis and epidemiology of sexually transmitted blood diseases. PMID:25866106

  10. HBV vaccination of HCV-infected patients with occult HBV infection and anti-HBc-positive blood donors

    Directory of Open Access Journals (Sweden)

    J.S.F. Pereira

    2006-04-01

    Full Text Available Anti-HBc positivity is a frequent cause of donation rejection at blood banks. Hepatitis B virus (HBV infection may also occur in HBsAg-negative patients, a situation denoted occult infection. Similarly, very low levels of HBV-DNA have also been found in the sera of patients with chronic hepatitis C virus (HCV infection, even in the absence of serum HBsAg. Initially we searched for HBV-DNA in serum of 100 blood donors and 50 HCV-infected patients who were HBsAg negative/anti-HBc positive by nested-PCR and by an HBV monitor commercial test for HBV-DNA. Anti-HBs seroconversion rates were measured in 100 blood donors and in 22 patients with chronic HCV infection after HBV vaccination to determine if the HBV vaccination could eliminate an occult HBV infection in these individuals. Occult HBV infection was detected in proportionally fewer blood donors (6/100 = 6% than chronic hepatitis C patients (12/50 = 24% (P 0.05. All subjects who were HBV-DNA(+ before the first dose of HBV vaccine (D1, became HBV-DNA(- after D1, D2, and D3. Among 22 HCV-positive patients, 10 HBV-DNA(+ and 12 HBV-DNA(-, seroconversion was observed in 9/10 (90% HBV-DNA(+ and in 9/12 (75% HBV-DNA(- subjects (P > 0.05. The disappearance of HBV-DNA in the majority of vaccinated patients suggests that residual HBV can be eliminated in patients with occult infection.

  11. Undetectable hepatitis C virus RNA during syphilis infection in two HIV/HCV-co-infected patients

    DEFF Research Database (Denmark)

    Salado-Rasmussen, Kirsten; Knudsen, Andreas; Krarup, Henrik Bygum;

    2014-01-01

    BACKGROUND: Treponema pallidum, the causative agent of syphilis, elicits a vigorous immune response in the infected host. This study sought to describe the impact of syphilis infection on hepatitis C virus (HCV) RNA levels in patients with HIV and chronic HCV infection. METHODS: Patients with...... chronic HIV/HCV and syphilis co-infection were identified by their treating physicians from 1 October 2010 to 31 December 2013. Stored plasma samples obtained before, during, and after syphilis infection were analysed for interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor alpha (TNF......-α), interferon gamma (IFN-γ), and IFN-γ-inducible protein 10 kDa (IP-10). RESULTS: Undetectable HCV RNA at the time of early latent syphilis infection was observed in 2 patients with HIV and chronic HCV infection. After treatment of the syphilis infection, HCV RNA levels increased again in patient 1, whereas...

  12. HCV and HIV infection and co-infection: injecting drug use and sexual behavior, AjUDE-Brasil I Project Infecções e co-infecções pelos vírus HCV e HIV: uso de drogas injetáveis e comportamento sexual, Projeto AjUDE-Brasil I

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    Keli Bahia Felicíssimo Zocratto

    2006-04-01

    Full Text Available This study aimed to characterize sexual and drug-use behaviors in injecting drug users (IDUs in relation to single hepatitis C virus (HCV and human immunodeficiency virus (HIV infection and HCV/HIV co-infection. The sample consisted of 272 IDUs enrolled in the AjUDE-Brasil I Project, a cross-sectional multi-center study conducted in five Brazilian cities in 1998. Data were collected with a structured questionnaire using self-reported risk behavior, and HCV and HIV serological status used ELISA on filter paper. IDUs were clustered in four distinct groups: HCV/HIV seronegative; HCV mono-infected; HIV mono-infected; and HCV/HIV co-infected. Active sharing of injecting equipment was associated with HCV infection (p = 0.001. Sexual behavior variables, especially male same-sex sexual relations, were consistently associated with HIV infection. HCV/HIV co-infection was associated with both sexual and drug use variables. It was possible to distinguish different behavioral indicators for HCV and HIV infection and co-infection in this population.Este estudo objetivou analisar grupos de usuários de drogas injetáveis (UDIs infectados e co-infectados pelos vírus da hepatite C (HCV e da imunodeficiência adquirida (HIV, em relação ao comportamento sexual e uso de drogas. A população de estudo foi composta por 272 UDIs participantes do Projeto AjUDE-Brasil I, estudo transversal multicêntrico realizado em cinco cidades brasileiras, em 1998. Os dados analisados foram coletados através de entrevistas estruturadas e testes sorológicos, utilizando-se papel filtro e a técnica ELISA, para HIV e HCV. Os UDIs foram agrupados em quatro grupos sorológicos distintos, a saber: (1 soronegativos, (2 monoinfectados pelo HCV, (3 monoinfectados pelo HIV e (4 co-infectados. Relato de ter "dado seringa", na vida, apresentou-se significantemente associado à infecção pelo HCV (p = 0,001. Em relação à infecção pelo HIV, variáveis de comportamento sexual, em

  13. Successful Integration of Hepatitis C Virus Point-of-Care Tests into the Denver Metro Health Clinic.

    Science.gov (United States)

    Jewett, A; Al-Tayyib, A A; Ginnett, L; Smith, B D

    2013-01-01

    Background. The Centers for Disease Control and Prevention (CDC) recommends testing and linkage to care for persons most likely infected with hepatitis C virus (HCV), including persons with human immunodeficiency virus. We explored facilitators and barriers to integrating HCV point-of-care (POC) testing into standard operations at an urban STD clinic. Methods. The OraQuick HCV rapid antibody test was integrated at the Denver Metro Health Clinic (DMHC). All clients with at least one risk factor were offered the POC test. Research staff conducted interviews with clients (three HCV positive and nine HCV negative). Focus groups were conducted with triage staff, providers, and linkage-to-care counselors. Results. Clients were pleased with the ease of use and rapid return of results from the HCV POC test. Integrating the test into this setting required more time but was not overly burdensome. While counseling messages were clear to staff, clients retained little knowledge of hepatitis C infection or factors related to risk. Barriers to integrating the HCV POC test into clinic operations were loss to follow-up and access to care. Conclusion. DMHC successfully integrated HCV POC testing and piloted a HCV linkage-to-care program. Providing testing opportunities at STD clinics could increase identification of persons with HCV infection. PMID:24455220

  14. Successful Integration of Hepatitis C Virus Point-of-Care Tests into the Denver Metro Health Clinic

    Directory of Open Access Journals (Sweden)

    A. Jewett

    2013-01-01

    Full Text Available Background. The Centers for Disease Control and Prevention (CDC recommends testing and linkage to care for persons most likely infected with hepatitis C virus (HCV, including persons with human immunodeficiency virus. We explored facilitators and barriers to integrating HCV point-of-care (POC testing into standard operations at an urban STD clinic. Methods. The OraQuick HCV rapid antibody test was integrated at the Denver Metro Health Clinic (DMHC. All clients with at least one risk factor were offered the POC test. Research staff conducted interviews with clients (three HCV positive and nine HCV negative. Focus groups were conducted with triage staff, providers, and linkage-to-care counselors. Results. Clients were pleased with the ease of use and rapid return of results from the HCV POC test. Integrating the test into this setting required more time but was not overly burdensome. While counseling messages were clear to staff, clients retained little knowledge of hepatitis C infection or factors related to risk. Barriers to integrating the HCV POC test into clinic operations were loss to follow-up and access to care. Conclusion. DMHC successfully integrated HCV POC testing and piloted a HCV linkage-to-care program. Providing testing opportunities at STD clinics could increase identification of persons with HCV infection.

  15. Frequency distribution of HCV genotypes among chronic hepatitis C patients of Khyber Pakhtunkhwa

    OpenAIRE

    Azam Sadiq; Ali Ijaz; Ali Sajid; Ahmad Bashir

    2011-01-01

    Abstract Background Hepatitis C Virus (HCV) genotypes frequency is important for the predication of response to therapy and duration of treatment. Despite variable response rates experienced in the case of Interferon (IFN) -based therapies, there was scarcity of data on HCV genotypes frequency in Khyber Pakhtunkhwa (KPK). Study Design A total of 200 blood samples were collected from chronic HCV patients prior to the initiation of anti-viral therapy. The study population included patients from...

  16. Response rates of standard interferon therapy in chronic HCV patients of Khyber Pakhtunkhwa (KPK)

    OpenAIRE

    Ahmad Bashir; Ali Sajid; Ali Ijaz; Azam Sadiq; Bashir Shumaila

    2012-01-01

    Abstract Background Interferon based therapy is used to eradicate the Hepatitis C Virus from the bodies of the infected individuals. HCV is highly prevalent in Khyber Pakhtunkhwa (KPK) that is why it is important to determine the response of standard interferon based therapy in Chronic HCV patients of the region. Study design A total of 174 patients were selected for interferon based therapy. The patients were selected from four different regions of KPK. After confirmation of active HCV infec...

  17. Development of mouse hepatocyte lines permissive for hepatitis C virus (HCV.

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    Hussein Hassan Aly

    Full Text Available The lack of a suitable small animal model for the analysis of hepatitis C virus (HCV infection has hampered elucidation of the HCV life cycle and the development of both protective and therapeutic strategies against HCV infection. Human and mouse harbor a comparable system for antiviral type I interferon (IFN induction and amplification, which regulates viral infection and replication. Using hepatocytes from knockout (ko mice, we determined the critical step of the IFN-inducing/amplification pathways regulating HCV replication in mouse. The results infer that interferon-beta promoter stimulator (IPS-1 or interferon A receptor (IFNAR were a crucial barrier to HCV replication in mouse hepatocytes. Although both IFNARko and IPS-1ko hepatocytes showed a reduced induction of type I interferons in response to viral infection, only IPS-1-/- cells circumvented cell death from HCV cytopathic effect and significantly improved J6JFH1 replication, suggesting IPS-1 to be a key player regulating HCV replication in mouse hepatocytes. We then established mouse hepatocyte lines lacking IPS-1 or IFNAR through immortalization with SV40T antigen. Expression of human (hCD81 on these hepatocyte lines rendered both lines HCVcc-permissive. We also found that the chimeric J6JFH1 construct, having the structure region from J6 isolate enhanced HCV replication in mouse hepatocytes rather than the full length original JFH1 construct, a new finding that suggests the possible role of the HCV structural region in HCV replication. This is the first report on the entry and replication of HCV infectious particles in mouse hepatocytes. These mouse hepatocyte lines will facilitate establishing a mouse HCV infection model with multifarious applications.

  18. A clinical, epidemological, laboratorial, histological and ultrasonographical evaluation of anti-HCV EIA-2 positive blood donors Avaliação clínica, epidemiológica, laboratorial, histológica e ultrassonográfica de doadores de sangue anti-HCV EIA-2 positivos

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    Fernando L. GONÇALES JR

    2000-06-01

    Full Text Available Between 1992 and 1997, 790 blood donors with anti-HCV EIA-2 strongly reagent (relationship between the sample optical density/cut-off > 3 detected at the blood bank serological screening, were evaluated in ambulatory environment. They were all negative for Chagas disease, syphilis, hepatitis B (HBsAg and AIDS. Blood samples were collected at the first ambulatorial evaluation, for hemogram, biochemical tests and new serological tests for HCV (anti-HCV EIA-2. In blood samples of 226 repeatedly reagent anti-HCV EIA-2 blood donors, supplementary "immunoblot" test for HCV (RIBA-2 was used. In 209 donors, the presence of HCV-RNA was investigated by the PCR test. The abdominal ultrasonography was realized in 366 donors. In 269 patients liver biopsy was performed for the histopathological study. The follow-up of blood donors showed that 95.6% were repeatedly EIA-2 reagent, 94% were symptomless and denied any hepatitis history, with only 2% mentioning previous jaundice. In 47% of this population at least one risk factor has been detected for the HCV transmission, the use of intravenous drugs being the main one (27.8%. Blood transfusion was the second factor for HCV transmission (27.2%. Hepatomegaly was detected in 54% of the cases. Splenomegaly and signs of portal hypertension have seldom been found in the physical examination, indicating a low degree of hepatic compromising in HCV. Abdominal ultrasound showed alterations in 65% of the subjects, being the steatosis the most frequent (50%. In 83.5% of the donors submitted to the liver biopsy, the histopathological exam showed the presence of chronic hepatitis, usually classified as active (89% with mild or moderate grade in most of the cases (99.5%. The histopathological exam of the liver was normal in 1.5% of blood donors. The RIBA-2 test and the HCV-RNA investigation by PCR were positive in respectively 91.6 and 75% of the anti-HCV EIA-2 reagent donors. The HCV-RNA research was positive in 82% of the

  19. Host APOBEC3G Protein Inhibits HCV Replication through Direct Binding at NS3

    OpenAIRE

    ZHU, YAN-PING; Peng, Zong-Gen; Wu, Zhou-Yi; Jian-rui LI; Huang, Meng-Hao; Si, Shu-Yi; Jiang, Jian-Dong

    2015-01-01

    Human APOBEC3G (hA3G) is a cytidine deaminase that restricts replication of certain viruses. We have previously reported that hA3G was a host restriction factor against hepatitis C virus (HCV) replication, and hA3G stabilizers showed a significant inhibitory activity against HCV. However, the molecular mechanism of hA3G against HCV remains unknown. We show in this study that hA3G’s C-terminal directly binds HCV non-structural protein NS3 at its C-terminus, which is responsible for NS3’s helic...

  20. Phenotypic characterization of lymphocytes in HCV/HIV co-infected patients.

    LENUS (Irish Health Repository)

    Roe, Barbara

    2009-02-01

    While hepatitis C virus (HCV)-specific immune responses are attenuated in HCV\\/HIV co-infected patients compared to those infected with HCV alone, the reasons for this remain unclear. In this study, the proportions of regulatory, naïve, and memory T cells, along with chemokine receptor expression, were measured in co-infected and mono-infected patients to determine if there is an alteration in the phenotypic profile of lymphocytes in these patients. HCV\\/HIV co-infected patients had increased proportions of CD4(+) naïve cells and decreased proportions of CD4(+) effector cells when compared to HCV mono-infected patients. The proportions of CD4(+) Tregs and CD4(+) CXCR3(+) T cells were also significantly lower in co-infected patients. A decrease in CD4(+) Tregs and subsequent loss of immunosuppressive function may contribute to the accelerated progression to liver disease in co-infected individuals. Dysregulation of immune responses following reduction in the proportions of CD4(+) CXCR3(+) Th-1 cells may contribute to the reduced functional capacity of HCV-specific immune responses in co-infected patients. The findings of this study provide new information on the T-cell immunophenotype in HCV\\/HIV co-infected patients when compared to those infected with HCV alone, and may provide insight into why cell-mediated immune responses are diminished during HCV infection.

  1. Hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infections in alcoholics.

    Science.gov (United States)

    Prakash, Om; Mason, Andrew; Luftig, Ronald B; Bautista, Abraham P

    2002-07-01

    Approximately 400,000 individuals in the United States are co-infected with hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) and it is likely that almost one in two of these subjects consumes alcohol. The majority of these patients suffer an accelerated course of liver disease as manifested by the onset of cirrhosis within 5 to 10 years of developing HCV infection, as well as an increased risk of developing hepatocellular carcinoma (HCC). It is thought that chronic alcohol abuse mediates liver damage as a result of increased production of free radicals and proinflammatory cytokines. In the setting of chronic HCV infection, alcohol ingestion has an additional effect of diminishing immune clearance and increasing viral burden to hasten the onset of cirrhosis and HCC. Likewise, chronic HCV and HIV-1 co-infection results in a net increase in HCV burden; higher prevalence rates of HCV transmission to sexual partners and offspring, as well as an accelerated progression to end stage liver disease as compared to individuals with HCV infection alone. Thus, the synergistic effects of alcohol abuse and HIV-1 greatly impact on the morbidity and mortality for patients with HCV coinfection. Ultimately, this cumulative disease process will require far more aggressive management with abstinence and counseling for alcohol abuse; highly active antiretroviral therapy (HAART) for HIV infection and combination anti-viral therapy for HCV infection to stem the rapid progression to end stage liver disease. PMID:12086918

  2. Structural basis of hepatitis C virus neutralization by broadly neutralizing antibody HCV1

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Leopold; Giang, Erick; Robbins, Justin B.; Stanfield, Robyn L.; Burton, Dennis R.; Wilson, Ian A.; Law, Mansun (Scripps)

    2012-10-29

    Hepatitis C virus (HCV) infects more than 2% of the global population and is a leading cause of liver cirrhosis, hepatocellular carcinoma, and end-stage liver diseases. Circulating HCV is genetically diverse, and therefore a broadly effective vaccine must target conserved T- and B-cell epitopes of the virus. Human mAb HCV1 has broad neutralizing activity against HCV isolates from at least four major genotypes and protects in the chimpanzee model from primary HCV challenge. The antibody targets a conserved antigenic site (residues 412-423) on the virus E2 envelope glycoprotein. Two crystal structures of HCV1 Fab in complex with an epitope peptide at 1.8-{angstrom} resolution reveal that the epitope is a {beta}-hairpin displaying a hydrophilic face and a hydrophobic face on opposing sides of the hairpin. The antibody predominantly interacts with E2 residues Leu{sup 413} and Trp{sup 420} on the hydrophobic face of the epitope, thus providing an explanation for how HCV isolates bearing mutations at Asn{sup 415} on the same binding face escape neutralization by this antibody. The results provide structural information for a neutralizing epitope on the HCV E2 glycoprotein and should help guide rational design of HCV immunogens to elicit similar broadly neutralizing antibodies through vaccination.

  3. 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.

  4. HIV-1 Vpr increases HCV replication through VprBP in cell culture.

    Science.gov (United States)

    Yan, Yanling; Huang, Fang; Yuan, Ting; Sun, Binlian; Yang, Rongge

    2016-09-01

    Coinfection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) occurs at a high frequency, in which HIV shows a promotion of HCV-derived liver diseases. However, the mechanism of how this occurs is not well understood. Our previous work has demonstrated that the HIV-1 accessory protein Vpr enhances HCV RNA replication in cell culture. Because Vpr performs most of its functions through host protein VprBP (DCAF1), the role of VprBP in the regulation of HCV by Vpr was investigated in this study. We found that the Vpr mutant Q65R, which is deficient in VprBP binding, could not enhance HCV replication. Furthermore, Vpr-mediated enhancement of HCV replication was severely diminished in VprBP knockdown cells. In addition, an inhibitor of Cullin RING E3 ligases, MLN4924, impaired the function of Vpr during HCV replication. Together, these results suggest that Vpr promotes HCV replication in a VprBP-dependent manner, and that the activity of Cullin RING E3 ligases is essential to this process. In conclusion, our findings demonstrate that HIV-1 Vpr makes the cellular environment more suitable for HCV replication, which might relate with the host ubiquitination system. PMID:27460548

  5. Increased microRNA-155 expression in the serum and peripheral monocytes in chronic HCV infection

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    Bala Shashi

    2012-07-01

    Full Text Available Abstract Background Hepatitis C Virus (HCV, a single stranded RNA virus, affects millions of people worldwide and leads to chronic infection characterized by chronic inflammation in the liver and in peripheral immune cells. Chronic liver inflammation leads to progressive liver damage. MicroRNAs (miRNA regulate inflammation (miR-155, -146a and -125b as well as hepatocyte function (miR-122. Methods Here we hypothesized that microRNAs are dysregulated in chronic HCV infection. We examined miRNAs in the circulation and in peripheral monocytes of patients with chronic HCV infection to evaluate if specific miRNA expression correlated with HCV infection. Results We found that monocytes from chronic HCV infected treatment-naïve (cHCV but not treatment responder patients showed increased expression of miR-155, a positive regulator of TNFα, and had increased TNFα production compared to monocytes of normal controls. After LPS stimulation, miR-155 levels were higher in monocytes from cHCV patients compared to controls. MiR-125b, which has negative regulatory effects on inflammation, was decreased in cHCV monocytes compared to controls. Stimulation of normal monocytes with TLR4 and TLR8 ligands or HCV core, NS3 and NS5 recombinant proteins induced a robust increase in both miR-155 expression and TNFα production identifying potential mechanisms for in vivo induction of miR-155. Furthermore, we found increased serum miR-155 levels in HCV patients compared to controls. Serum miR-125b and miR-146a levels were also increased in HCV patients. Serum levels of miR-122 were elevated in cHCV patients and correlated with increased ALT and AST levels and serum miR-155 levels. Conclusion In conclusion, our novel data demonstrate that miR-155, a positive regulator of inflammation, is upregulated both in monocytes and in the serum of patients with chronic HCV infection. Our study suggests that HCV core, NS3, and NS5 proteins or TLR4 and TLR8 ligands can mediate

  6. Hepatitis C Virus Treatment Access Among Human Immunodeficiency Virus and Hepatitis C Virus (HCV)-Coinfected People Who Inject Drugs in Guangzhou, China: Implications for HCV Treatment Expansion.

    Science.gov (United States)

    Chu, Carissa E; Wu, Feng; He, Xi; Zhou, Kali; Cheng, Yu; Cai, Weiping; Geng, Elvin; Volberding, Paul; Tucker, Joseph D

    2016-04-01

    Background.  Hepatitis C virus (HCV) treatment access among human immunodeficiency virus (HIV)/HCV-coinfected people who inject drugs is poor, despite a high burden of disease in this population. Understanding barriers and facilitators to HCV treatment uptake is critical to the implementation of new direct-acting antivirals. Methods.  We conducted in-depth interviews with patients, physicians, and social workers at an HIV treatment facility and methadone maintenance treatment centers in Guangzhou, China to identify barriers and facilitators to HCV treatment. We included patients who were in various stages of HCV treatment and those who were not treated. We used standard qualitative methods and organized data into themes. Results.  Interview data from 29 patients, 8 physicians, and 3 social workers were analyzed. Facilitators and barriers were organized according to a modified Consolidated Framework for Implementation Research schematic. Facilitators included patient trust in physicians, hope for a cure, peer networks, and social support. Barriers included ongoing drug use, low HCV disease knowledge, fragmented reimbursement systems, HIV exceptionalism, and stigma. Conclusions.  Expanding existing harm reduction programs, HIV treatment programs, and social services may facilitate scale-up of direct-acting antivirals globally. Improving integration of ancillary social and mental health services within existing HIV care systems may facilitate HCV treatment access. PMID:27419150

  7. Correlates of HIV, HBV, HCV and syphilis infections among prison inmates and officers in Ghana: A national multicenter study

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    Asare Isaac

    2008-03-01

    Full Text Available Abstract Background Prisons are known to be high-risk environments for the spread of bloodborne and sexually transmitted infections. Prison officers are considered to have an intermittent exposure potential to bloodborne infectious diseases on the job, however there has been no studies on the prevalence of these infections in prison officers in Ghana. Methods A national multicenter cross-sectional study was undertaken on correlates of human immunodeficiency virus (HIV, hepatitis B virus (HBV, hepatitis C virus (HCV, and syphilis infections in sample of prison inmates and officers from eight of ten regional central prisons in Ghana. A total of 1366 inmates and 445 officers were enrolled between May 2004 and December 2005. Subjects completed personal risk-factor questionnaire and provided blood specimens for unlinked anonymous testing for presence of antibodies to HIV, HCV and Treponema pallidum; and surface antigen of HBV (HBsAg. These data were analyzed using both univariate and multivariate techniques. Results Almost 18% (1336 of 7652 eligible inmates and 21% (445 of 2139 eligible officers in eight study prisons took part. Median ages of inmates and officers were 36.5 years (range 16–84 and 38.1 years (range 25–59, respectively. Among inmates, HIV seroprevalence was 5.9%, syphilis seroprevalence was 16.5%, and 25.5% had HBsAg. Among officers tested, HIV seroprevalence was 4.9%, HCV seroprevalence was 18.7%, syphilis seroprevalence was 7.9%, and 11.7% had HBsAg. Independent determinants for HIV, HBV and syphilis infections among inmates were age between 17–46, being unmarried, being illiterate, female gender, being incarcerated for longer than median time served of 36 months, history of homosexuality, history of intravenous drug use, history of sharing syringes and drug paraphernalia, history of participation in paid sexual activity, and history of sexually transmitted diseases. Independent determinants for HIV, HBV, HCV and syphilis

  8. HCV对HIV/HCV共感染患者病情进展的影响%Effect of HCV on disease progression in patients with HIV/HCV coinfection

    Institute of Scientific and Technical Information of China (English)

    刘金花; 赵艳; 孙焕芹; 刘宁; 乔桂芳; 王子康; 徐杰; 李昂; 张永宏

    2014-01-01

    -nine patients with HIV/HCV coinfection and 20 patients with HIV infection alone,who visited Beijing YouAn hospital for follow-up in August 2012,were enrolled.The two groups of patients were matched for age,sex,time and route of HIV infection,and HIV subtypes.The liver function and fibrosis were evaluated by biochemical testing of peripheral blood and FibroScan.CD4 +and CD8 +T cell counts were determined by flow cytometry.Results The levels of alanine aminotransferase,aspartate aminotransferase,and total bilirubin for the HIV/HCV coinfection group were 76.16 ±81.25 U/L,87.66 ±71.32 U/L,and 14.21 ±9.56μmol/L,respectively,significantly higher than those for the HIV infection group (27.74 ±20.63 U/L,45.65 ±16.95 U/L,and 10.26 ± 3.22 μmol/L)(P=0.004,0.005,and 0.046).Compared with the HIV infection group,the HIV/HCV coinfection group had a nonsig-nificantly increased liver stiffness (t=1.889,P=0.080),a significantly higher viral load (3.66 ±0.97 lg copies/ml vs 3.02 ±0.90 lg copies/ml,t=2.251,P=0.030),significantly lower CD4 +T cell count and CD4 +/CD8 +ratio (374.25 ±185.48 cells/μl vs 496.45 ± 230.98 cells/μl,P=0.048;0.33 ±0.17 vs 0.46 ±0.27,P=0.043),and a nonsignificantly higher incidence of AIDS (27.59% vs 5.00%,P=0.063).Conclusion HCV exacerbates liver damage,enhances HIV replication,increases the impairment of immune func-tion in patients with HIV/HCV coinfection,so it can accelerate the disease progression in these patients.

  9. Socioeconomic status in HCV infected patients – risk and prognosis

    Directory of Open Access Journals (Sweden)

    Oml

    2013-05-01

    Full Text Available Lars Haukali Omland,1 Merete Osler,2 Peter Jepsen,3,4 Henrik Krarup,5 Nina Weis,6 Peer Brehm Christensen,7 Casper Roed,1 Henrik Toft Sørensen,3 Niels Obel1 On behalf of the DANVIR Cohort Study1Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 2Research Center for Prevention and Health, Copenhagen University Hospital, Glostrup Hospital, Glostrup, Denmark; 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Medicine V (Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 5Department of Clinical Biochemistry, Aalborg Hospital, Aalborg, Denmark; 6Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Denmark; 7Department of Infectious Diseases, Odense University Hospital, Odense, DenmarkBackground and aims: It is unknown whether socioeconomic status (SES is a risk factor for hepatitis C virus (HCV infection or a prognostic factor following infection.Methods: From Danish nationwide registries, we obtained information on three markers of SES: employment, income, and education. In a case control design, we examined HCV infected patients and controls; conditional logistic regression was employed to obtain odds ratios (ORs for HCV infection for each of the three SES markers, adjusting for the other two SES markers, comorbidity, and substance abuse. In a cohort design, we used Cox regression analysis to compute mortality rate ratios (MRRs for each of the three SES markers, adjusting for the other two SES markers, comorbidity level, age, substance abuse, and gender.Results: When compared to employed persons, ORs for HCV infection were 2.71 (95% confidence interval [CI]: 2.24–3.26 for disability pensioners and 2.24 (95% CI: 1.83–2.72 for the unemployed. When compared to persons with a high income, ORs were 1.64 (95% CI: 1.34–2.01 for low income persons and 1.19 (95% CI: 1.02–1.40 for

  10. Potential for Drug-Drug Interactions between Antiretrovirals and HCV Direct Acting Antivirals in a Large Cohort of HIV/HCV Coinfected Patients

    OpenAIRE

    Poizot-Martin, Isabelle; Naqvi, Alissa; Obry-Roguet, Véronique; Valantin, Marc-Antoine; Cuzin, Lise; Billaud, Eric; Cheret, Antoine; Rey, David; Jacomet, Christine; Duvivier, Claudine; Pugliese, Pascal; Pradat, Pierre; Cotte, Laurent

    2015-01-01

    Objectives Development of direct acting antivirals (DAA) offers new benefits for patients with chronic hepatitis C. The combination of these drugs with antiretroviral treatment (cART) is a real challenge in HIV/HCV coinfected patients. The aim of this study was to describe potential drug-drug interactions between DAAs and antiretroviral drugs in a cohort of HIV/HCV coinfected patients. Methods Cross-sectional study of all HIV/HCV coinfected patients attending at least one visit in 2012 in the...

  11. 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

  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

    Directory of Open Access Journals (Sweden)

    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. Safety of interferon treatment for chronic HCV hepatitis

    Institute of Scientific and Technical Information of China (English)

    D Festi; L Sandri; G Mazzella; E Roda; T Sacco; T Staniscia; S Capodicasa; A Vestito; A Colecchia

    2004-01-01

    Hepatitis C is a major cause of liver-related morbidity and mortality worldwide, In fact, chronic hepatitis C is considered as one of the primary causes of chronic liver disease, cirhosis and hepatocellular carcinoma, and is the most common reason for liver transplantation. The primary objectives for the treatment of HCV-related chronic hepatitis is to eradicate infection and prevent progression of the disease. The treatment has evolved from the use of α-interferon (TFNα)alone to the combination of IFNα plus ribavirin, with a significant improvement in the overall efficacy, and to the newer PEG-IFNs which have further increased the virological response, used either alone or in combination with ribavirin.Despite these positive results, in terms of efficacy, concerns are related to the safety and adverse events. Many patients must reduce the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable percentage of subjects are not suitable owing to intolerance toward drugs. IFNβ represents a potential therapeutic alternative for the treatment of chronic viral hepatitis and in some countries it plays an important role in therapeutic protocols. Aim of the present paper was to review available data on the safety of IFNβ treatment in HCV-related chronic hepatitis.The rates of treatment discontinuation and/or dose modification due to the appearance of severe side effects during IFNβ are generally low and in several clinical studies no requirements for treatment discontinuation and/or dose modifications have been reported. The most frequent side effects experienced during IFNβ treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No differences in terms of side-effect frequency and severity between responders and non-responders have been reported.A more recent study, performed to compare IFNβ alone or in combination with ribavirin, confirmed the good safety profile of both treatments. Similar trends of adverse event

  14. HCV Animal Models: A Journey of More than 30 Years

    OpenAIRE

    Philip Meuleman; Geert Leroux-Roels

    2009-01-01

    In the 1970s and 1980s it became increasingly clear that blood transfusions could induce a form of chronic hepatitis that could not be ascribed to any of the viruses known to cause liver inflammation. In 1989, the hepatitis C virus (HCV) was discovered and found to be the major causative agent of these infections. Because of its narrow ropism, the in vivo study of this virus was, especially in the early days, limited to the chimpanzee. In the past decade, several alternative animal models hav...

  15. Cancer stem cells generated by alcohol, diabetes, and HCV

    OpenAIRE

    Machida, Keigo; Chen, Chia-Lin; Liu, Jian-Chang; Kashiwabara, Claudine; Feldman, Douglas; French, Samuel W.; Sher, Linda; Hyeongnam, Jeong Joseph; Tsukamoto, Hidekazu

    2012-01-01

    Cancer stem cells (Tumor-initiating stem-like cells: TISCs) are resistant to chemotherapy and are associated with metastatic hepatocellular carcinoma (HCC), which is commonly observed in hepatitis C virus (HCV)-infected patients with obesity or alcohol abuse. However, it is unknown whether the TLR4-NANOG pathway serves as a universal oncogenic signaling in the genesis of TISCs and HCC. We aimed to determine whether Tlr4 is a putative proto-oncogene for TISCs in liver oncogenesis due to differ...

  16. Prevalence, attitudes and knowledge about HIV HBV and HCV infections among inmates in prisons Prilep and Bitola--a pilot study.

    Science.gov (United States)

    Jovanovska, Tanja; Kocic, Biljana; Stojcevska, Viktorija P

    2014-06-01

    Prisons are associates as facilities liable of high risk of infection disease, as a result of the possibility of transmission of infections in prisons surroundings. Investigations carried out in correctional facilities around the world have shown a high prevalence of blood borne hepatitis viruses and HIV. The study was aimed at confirming prevalence of HIV hepatitis B and hepatitis C among prisoners in Bitola's, and Prilep's prisons, existing of co-infection as well to assess knowledge and attitudes related to HIV, HBV and HCV infections. In this cross-sectional study 200 prisoners have participated, providing answers to structured questionnaire and in order to analyze blood for HIV, HBV and HCV, rapid blood tests in detecting antibodies has been used. Prevalence of HCV is 0.20, HBV 0.17 and HIV prevalence is 0. Co-infection prevalence of HCV/HBV is 0.07 from the total number of examinees. As for the manner of infection with HIV virus 22% are familiar with the fact that persons cannot be infected by HIV if they have only one sexual partner who is not infected and have no other partners, and for the protection of HIV and Hepatitis B by correct use of condoms-58% have given correct answers. PMID:25144968

  17. Hepatitis B (HBV), Hepatitis C (HCV) and Hepatitis Delta (HDV) Viruses in the Colombian Population—How Is the Epidemiological Situation?

    Science.gov (United States)

    Alvarado-Mora, Mónica Viviana; Gutierrez Fernandez, María Fernanda; Gomes-Gouvêa, Michele Soares; de Azevedo Neto, Raymundo Soares; Carrilho, Flair José; Pinho, João Renato Rebello

    2011-01-01

    Background Viral hepatitis B, C and delta still remain a serious problem worldwide. In Colombia, data from 1980s described that HBV and HDV infection are important causes of hepatitis, but little is known about HCV infection. The aim of this study was to determine the currently frequency of HBV, HCV and HDV in four different Colombian regions. Methodology/Principal Findings This study was conducted in 697 habitants from 4 Colombian departments: Amazonas, Chocó, Magdalena and San Andres Islands. Epidemiological data were obtained from an interview applied to each individual aiming to evaluate risk factors related to HBV, HCV or HDV infections. All samples were tested for HBsAg, anti-HBc, anti-HBs and anti-HCV markers. Samples that were positive to HBsAg and/or anti-HBc were tested to anti-HDV. Concerning the geographical origin of the samples, the three HBV markers showed a statistically significant difference: HBsAg (p = 0.033) and anti-HBc (pAmazonas and Magdalena departments. Isolated anti-HBs (a marker of previous vaccination) frequencies were: Chocó (53.26%), Amazonas (32.88%), Magdalena (17.0%) and San Andrés (15.33%) - pAmazonas department showed the highest frequency for anti-HCV marker (5.68%), while the lowest frequency was found in San Andrés Island (0.66%). Anti-HDV was found in 9 (5.20%) out of 173 anti-HBc and/or HBsAg positive samples, 8 of them from the Amazonas region and 1 from them Magdalena department. Conclusions/Significance In conclusion, HBV, HCV and HDV infections are detected throughout Colombia in frequency levels that would place some areas as hyperendemic for HBV, especially those found in Amazonas and Magdalena departments. Novel strategies to increase HBV immunization in the rural population and to strengthen HCV surveillance are reinforced by these results. PMID:21559488

  18. Sieropositivitá per HIV, HBV e HCV negli utenti del Servizio di Tossicodipendenza di Formia (ASL di Latina

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    G. La Torre

    2003-05-01

    Full Text Available

    Obiettivi: valutare la prevalenza sieropositività per HIV, HBV e HCV nei tossicodipendenti afferenti al Ser.T di Formia (LT.

    Materiali e metodi: sono state consultate le cartelle cliniche degli afferenti al Ser.T. nel 2002, estraendo dati relativi ai parametri socio-demografici ed alle sieropositività. L’analisi statistica ha previsto l’impiego del test del χ2 e della regressione logistica multipla.

    Risultati: sono stati presi in considerazione 135 tossicodipendenti, di cui 103 (76.3% maschi e 32 (23.7% femmine. L’età mediana dell’inizio della tossicodipendenza e della presa in carico presso il servizio erano, rispettivamente, di 18 e di 23 anni. Il 94.1% dei tossicodipendenti risulta dipendente primariamente da eroina, il 5.2% da cocaina e lo 0.7% da alcol. Relativamente alle positività per i virus considerati, 7 soggetti (5.2% sono risultati positivi all’HIV, 23 (17% sieropositivi per HBV e 50 (37% sieropositivi per HCV. L’analisi multivariata mostra che sono associate alla sieropositività per HCV la sieropositività per HBV (OR = 3.87 e l’età della presa in carico presso il servizio superiore a 25 anni (OR = 1.88; alla sieropositività per HBV l’occupazione saltuaria (OR = 4.58, la HCV positività (OR = 4.41 e la HIV positività (OR = 5.39; alla sieropositività per HIV l’età della presa in carico presso il servizio superiore a 25 anni (OR = 4.94.

    Discussione: l’indagine ha messo in evidenza prevalenze di sieropositività per HCV, HBV e HIV decisamente inferiori a quelle registrate in altre realtà italiane ed internazionali. Una possibile spiegazione potrebbe essere ricercata nei bassi livelli di sieropositività per questi virus nella popolazione generale del Basso Lazio, o nella scarsa abitudine di scambiarsi le siringhe fra tossicodipendenti di questa area geografica.

  19. Response rates to standard interferon treatment in HCV genotype 3A

    International Nuclear Information System (INIS)

    Chronic Hepatitis C infection infects almost 130 to 170 million or approximately 2.2-3% of world's population. HCV is one of the main causes of chronic liver disease leading to progressive liver injury, fibrosis, cirrhosis and liver cancer. It is also one of the leading indications for liver transplantation worldwide. The objective of the study was to determine the response of treatment with standard Interferon and Ribazole in treatment native Hepatitis C infected patients. This quasi-experimental study was carried out at the Department of Medicine, KRL General Hospital Islamabad, from January 2003 to January 2005. A total of 250 patients were enrolled in this descriptive study. All patients were anti HCV positive, PCR positive for HCV RNA and had 3a genotype. A non-probability purposive sampling technique was applied to collect data. After taking a written and informed consent; specially designed performa containing the patient profile, family transmission, and baseline laboratory values was filled. Patients were treated with a set protocol of Interferon plus Ribavarin therapy (IFN alpha 2a, 3 mIU thrice weekly for 24 weeks plus Ribavarin 1,000 to 1,200 mg/day) for six months. Chi-Square tests were used to analyse the data. Primary end point was a sustained virological response (SVR) that is response assessed after six months of completion of treatment. Response rates to standard Interferon plus Ribazole therapy were studied over two years period. Out of the total of 250 patients, 60 patients were excluded; as 30 patients did not meet inclusion criteria, 23 patients were lost to follow. Seven patients declined treatment. Out of the 190 patients, 155 (81.6%) achieved End of Treatment Complete Response (EOTCR) whereas 35 (18.4%) were nonresponders (NR). These 155 patients, who showed complete response were followed for six months after the treatment to assess sustained viral response, which was seen in 112 (72.25%) patients whereas 43 (27.7%) were relapsers

  20. 75 FR 39035 - Housing Choice Voucher (HCV) Family Self-Sufficiency (FSS) Program

    Science.gov (United States)

    2010-07-07

    ... URBAN DEVELOPMENT Housing Choice Voucher (HCV) Family Self-Sufficiency (FSS) Program AGENCY: Office of... independence and self- sufficiency. Housing agencies consult with local officials to develop an Action Plan... Title of Proposal: Housing Choice Voucher (HCV) Family Self- Sufficiency (FSS) Program. OMB...

  1. Some Immunological, Hematological And Biochemical Parameters Characteristics Of The HCV Healthy Carrier

    International Nuclear Information System (INIS)

    The present study was aimed to identify some immunological, hematological and biochemical characteristics of the HCV healthy carrier state. Thirteen Egyptian HCV seropositive males who fulfilled the criteria of the HCV healthy carrier state were selected from 560 asymptomatic individuals. Fifteen age matched healthy HCV seronegative were used as control. Blood samples were withdrawn from all participants three times at six month interval to provide Leishmania stained smears, citrated plasma and sera. The following parameters were estimated: plasma prothrombin time and concentration, serum ALT and AST, L.E cells, hyper segmented neutrophils, cryo globulins, total IgM, albumin, C3, CIq immune complex and a-fetoprotein. Atypical lymphocyte and hyper segmented neutrophil proportion were determined from microscopical examination of Leishmania stained blood smears. Data from the present study showed that the HCV healthy carriers had significantly higher ALT, AST, prothrombin time, atypical lymphocytes and hyper segmented neutrophil proportion, serum C3, immune complex, IgM and a-fetoprotein than healthy HCV seronegative controls whereas serum albumin content did not change. In conclusion, the present data may suggest a role of the HCV in down regulation of the prothrombin synthesis and up regulation of the C3 production and immune complex formation and serum a-fetoprotein independently from hepatic damage. It also shows that atypical lymphocytes and hyper segmented neutrophils were increased in response to HCV infection

  2. 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.

  3. Valine, a Branched-Chain Amino Acid, Reduced HCV Viral Load and Led to Eradication of HCV by Interferon Therapy in a Decompensated Cirrhotic Patient

    OpenAIRE

    Kawaguchi, Takumi; Torimura, Takuji; Takata, Akio; Satomi, Susumu; Sata, Michio

    2012-01-01

    A decreased serum level of branched-chain amino acid (BCAA) is a distinctive metabolic disorder in patients with liver cirrhosis. Recently, BCAA has been reported to exert various pharmacological activities, and valine, which is a BCAA, has been shown to affect lipid metabolism and the immune system in in vivo experiments. However, the clinical impact of valine supplementation on viral hepatitis C virus (HCV) load has never been reported. Here, we first describe a case of HCV-related advanced...

  4. Hepatites pós-transfusionais na cidade de Campinas, SP, Brasil: II. Presença dos anticorpos anti-HBc e anti-HCV em candidatos a doadores de sangue e ocorrência de hepatites pós-transfusionais pelo vírus C nos receptores de sangue ou derivados Post-transfusional hepatitis in the city of Campinas, SP, Brazil: II- Presence of anti-HBc and anti-HCV antibodies in blood donors and occurrence of post-transfusional hepatitis C virus in recipients of blood or derivates

    Directory of Open Access Journals (Sweden)

    Fernando Lopes Gonçales Júnior

    1993-02-01

    Full Text Available Pesquisamos os anticorpos anti-HBc e anti-HCV em amostras de soros provenientes de 799 candidatos a doadores, que tiveram suas unidades de sangue ou derivados transfundidas a 111 receptores. O anti-HBc e o anti-HCV foram reagentes, em respectivamente 9 e 2,1% dos doadores testados. Observamos que entre os 111 receptores, 44 haviam recebido pelo menos uma unidade anti-HBc positiva e 67 haviam sido transfundidos somente com unidades anti-HBc negativas. Houve um risco 4,5 vezes maior de aquisição de hepatite por vírus C pelos receptores que receberam pelo menos uma unidade anti-HBc positiva Se a pesquisa do anti-HBc fosse realizada na triagem sorológica dos doadores de sangue, cerca de 56% dos casos de HVC nos receptores saiam evitados. A população de receptores que recebeu pelo menos uma unidade anti-HCV reagente, apresentou um risco 29 vezes maior de adquirir esta hepatite, quando comparada aos receptores transfundidos com todas as unidades anti-HCV negativas. A realização do teste para a pesquisa do anti-HCV na triagem dos doadores de sangue, preveniria 79% dos casos de HVC pós-transfusionais. Os candidatos a doadores brasileiros parecem ser acometidos simultânea ou sequencialmente, pelos vírus B e C das hepatites, pois, 44,4% dos doadores anti-HCV positivos, também foram anti-HBc positivos. A realização dos testes para as pesquisas dos anticorpos anti-HBc e anti-HCV, nas triagens hemoterápicas, está indicada para prevenir a transmissão de hepatites pós-transfusionais, em nosso meio.We have analysed anti-HBc and anti-HCV antibodies in serum samples from 799 donors which had their blood or derivates transfused to 111 recipients. Anti-HBc and anti-HCV were reactive in respectively 9 and 2.1% of the donors tested. We have observed that among the 111 recipients, 44 had received at least one positive anti-HBc unit and 67 had been transfused only with negative anti-HBc, units. The risk of developing hepatitis C virus was 4.5 times

  5. 4'-Substituted pyrimidine nucleosides lacking 5'-hydroxyl function as potential anti-HCV agents.

    Science.gov (United States)

    Shakya, Neeraj; Vedi, Satish; Liang, Chao; Yang, Fang; Agrawal, Babita; Kumar, Rakesh

    2014-03-01

    Hepatitis C virus (HCV) infection is one of the major health problems worldwide. If left untreated, it leads to liver cirrhosis, liver cancer and death. Herein, we report synthesis and anti-HCV activity of a new class of pyrimidine nucleosides possessing a 4'-carboxymethyl (9-16, 21 and 23) or 4'-carboxamide function (17-19 and 24). Among these, 10-12 (EC50=33.1-42.4 μM), 14 and 21 (EC50=43.4-59.5 μM) exhibited potent activity in HCV-1a replicon cells without any toxicity to parent Huh-7 cells (CC50=>829-1055 μM). The anti-HCV activities demonstrated by this unusual class of compounds were superior to that of ribavirin (EC50=81.9 μM). Further, the most active analog, 12, was found to interact synergistically with ribavirin to inhibit HCV RNA replication. PMID:24485784

  6. Characteristics of HCV positive patients in an Italian urban psychiatric unit

    Directory of Open Access Journals (Sweden)

    Azzoni Antonella

    2006-10-01

    Full Text Available Abstract Objectives 1 to assess the prevalence of hepatitis C virus (HCV infection in a population of acute psychiatric in-patients; 2 to find out relationships between HCV comorbidity and clinical features of psychiatric patients. Methods Prospective observational study in a 6-year period. Results 2396 cases (1492 patients were admitted in the considered period. Forty-two patients (2.8% were affected by HCV infection. HCV infection was more frequent in patients with less years of education, lower social class, lower last year best Global Assessment of Functioning score, more hostile or violent behavior in hospital, with a lifetime history of previous suicide attempt, and with substance-related disorders. Conclusion HCV infection in psychiatric patients constitutes a major threat to the health of psychiatric patients and is related with unfavorable social background, worse global functioning, hostile or violent behavior, substance-related disorders. It appears also to be a significant risk of suicidal behavior.

  7. Performance study of the automated immunoassay test anti-hepatitis C virus VIDAS® for the qualitative detection of antibodies anti-hepatitis C virus

    Directory of Open Access Journals (Sweden)

    Sara Salvetti

    2016-03-01

    Full Text Available Background and aims: Hepatitis C virus (HCV represents a major worldwide public health problem requiring global action for the diagnosis, treatment and prevention of this infection. HCV is the leading cause of chronic liver disease, including chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma and it is responsible for about 350,000 deaths yearly. Anti-HCV assays remain the first choice for screening HCV infection in most clinical laboratories. The anti-HCV VIDAS® (bioMérieux, Marcy L’Etoile, France test has been recently launched and we aimed to evaluate its performance compared with other widely used methods. Materials and methods: Routine anti-HCV screening of clinical samples was carried out on the ARCHITECT® i2000SR platform (Abbot Laboratories, Abbott Park, IL, USA; out of 8876 samples tested from October 2012 to May 2013, 70 sera with low positive anti-HCV results (1≤S/CO<8 were collected. These samples were tested for the presence of anti-HCV antibodies using anti-HCV VIDAS® and INNO-LIATM HCV score assays (Innogenetics NV, Ghent, Belgium. Results and conclusions: Positive anti-HCV results were obtained in 61.4% and 41.4% of sera tested with VIDAS® and INNO-LIATM, respectively. Concordance between methods was 63.2% for ARCHITECT® and VIDAS®, 42.6% for ARCHITECT® and INNO-LIATM, and 79.4% for VIDAS® and INNO-LIATM. Anti-HCV VIDAS® demonstrated superior specificity compared to the anti-HCV test ARCHITECT®; therefore, this assay has been introduced in our routine analysis as a second level screening test to select samples to be subjected to confirmatory anti- HCV immunoblot.

  8. Seroprevalence of anti-HCV antibodies among blood donors of north India

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    R N Makroo

    2013-01-01

    Full Text Available Background & objectives: Transfusion of blood and blood products although considered as a life saving treatment modality, but may lead to certain infectious and non-infectious complications in the recipients. The purpose of this analysis was to monitor the seroprevalence of anti-HCV antibody in the blood donor population in a hospital based blood bank in north India, to evaluate the trends over the years (2001-2011. Methods: Relevant information of all the blood donors who donated whole blood at the department of Transfusion Medicine, Indraprastha Apollo Hospitals, New Delhi from the January 1, 2001 to December 31, 2011 was retrieved from the departmental records. The number of donors who were found reactive for anti-HCV anatibodies was calculated. Results: Of the 2,06,022 blood donors, 1,93,661 were males and 12,361 were females. The percentage of whole blood donors found seroreactive for anti-HCV antibodies was 0.39 per cent (n=795. The seroprevalence of anti-HCV in male blood donors was 0.38 per cent (n=750 and the respective seroprevalence in female blood donors was 0.36 per cent (n=45. No significant change in the trend of HCV seroprevalence was observed over the period under consideration. Maximum seroprevalence of anti-HCV was observed in the age group of 18 to 30 yr (0.41% and the minimum in the age group of 51 to 60 yr (0.26%. Interpretation & conclusion: HCV seroprevalence in our study was 0.39 per cent and a decreasing trend with age was observed. No significant change in the trend of anti-HCV seroprevalence was seen over a decade. Since, no vaccine is presently available for immunization against HCV infection, transfusion transmitted HCV infection remains a potential threat to the safety of the blood supply.

  9. Natural killer KIR3DS1 is closely associated with HCV viral clearance and sustained virological response in HIV/HCV patients.

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    Antonio Rivero-Juarez

    Full Text Available AIM: To evaluate the influence of the presence of the killer cell immunoglobulin-like receptor (KIR 3DS1 on HCV treatment response in HIV/HCV genotype 1 co-infected patients. METHODS: HIV/HCV co-infected patients were included. KIR3DS1, their specific HLA-B ligands and IL28B gene were genotyped. Reductions of plasma HCV RNA levels between baseline and week 1, week 2 and week 4 were analyzed for IL28B genotype and KIR3DS1 (HLA Bw4 or Bw6. Rapid and sustained virological response (RVR and SVR rates were also analyzed. RESULTS: Sixty HIV/HCV genotype 1 co-infected patients were included. Patients with KIR3DS1 and Bw4 had higher rates of HCV viral decline than those who were not carriers of KIR3DS1 (week 1: p = 0.01; week 2: p = 0.038; week 4: p = 0.03. Patients carrying KIR3DS1/Bw4 had higher rates of RVR and SVR than those who did not carry KIR3DS1 (RVR: 46.15% versus 17.02%, p = 0.012; SVR: 63.6% versus 13 26.5%, p = 0.031. With respect to patients carrying the IL28B-CC genotype, those with KIR3DS1/Bw4 had greater rates of HCV viral clearance (week 1: p<0.001; week 2: p = 0.01; week 4: p = 0.02, RVR (p = 0.015 and SVR (p = 0.029 than those not carrying KIR3DS1. CONCLUSION: Our results show that the KIR3DS1 genotype has a positive effect on HCV viral clearance during the first weeks of Peg-IFN/RBV treatment in HCV/HCV co-infected patients bearing genotype 1, and higher RVR and SVR rates.

  10. SEC14L2 enables pan-genotype HCV replication in cell culture.

    Science.gov (United States)

    Saeed, Mohsan; Andreo, Ursula; Chung, Hyo-Young; Espiritu, Christine; Branch, Andrea D; Silva, Jose M; Rice, Charles M

    2015-08-27

    Since its discovery in 1989, efforts to grow clinical isolates of the hepatitis C virus (HCV) in cell culture have met with limited success. Only the JFH-1 isolate has the capacity to replicate efficiently in cultured hepatoma cells without cell culture-adaptive mutations. We hypothesized that cultured cells lack one or more factors required for the replication of clinical isolates. To identify the missing factors, we transduced Huh-7.5 human hepatoma cells with a pooled lentivirus-based human complementary DNA (cDNA) library, transfected the cells with HCV subgenomic replicons lacking adaptive mutations, and selected for stable replicon colonies. This led to the identification of a single cDNA, SEC14L2, that enabled RNA replication of diverse HCV genotypes in several hepatoma cell lines. This effect was dose-dependent, and required the continuous presence of SEC14L2. Full-length HCV genomes also replicated and produced low levels of infectious virus. Remarkably, SEC14L2-expressing Huh-7.5 cells also supported HCV replication following inoculation with patient sera. Mechanistic studies suggest that SEC14L2 promotes HCV infection by enhancing vitamin E-mediated protection against lipid peroxidation. This provides a foundation for development of in vitro replication systems for all HCV isolates, creating a useful platform to dissect the mechanisms by which cell culture-adaptive mutations act. PMID:26266980

  11. Most common genotypes and risk factors for HCV in Gaza strip: a cross sectional study

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    Abu-Jadallah Salah Y

    2009-07-01

    Full Text Available Abstract Background The present work aims at determining HCV genotypes in patients with chronic HCV infection, in Gaza strip, Palestine. The most common risk factors for HCV transmission were also evaluated in conjunction with the genotyping data. Results The study shows that there are only two major genotypes of HCV in Gaza Strip: Genotype 1 (subtypes 1a and 1b collectively contribute to 28.3% of the cases, and genotype 4 (subtypes 4a and 4c/d collectively contribute to 64.1% of the cases. Mixed infection with the two genotypes was also present among 7.6% of the cases. In this study a statistically significant relationship was established between the distribution of these genotypes and the patients' living place, traveling history, history of blood transfusion and history of surgical operations. Conclusion The present study is the first to link HCV genotyping in Gaza strip with its possible roots of transmission. Traveling to endemic countries, especially Egypt; blood transfusion and surgical operations are major roots of HCV infection in Gaza strip. The results indicate that iatrogenic and nosocomial procedures may be responsible for the majority of HCV infections in Gaza strip.

  12. Comparative Proteomics Reveals Important Viral-Host Interactions in HCV-Infected Human Liver Cells.

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    Shufeng Liu

    Full Text Available Hepatitis C virus (HCV poses a global threat to public health. HCV envelop protein E2 is the major component on the virus envelope, which plays an important role in virus entry and morphogenesis. Here, for the first time, we affinity purified E2 complex formed in HCV-infected human hepatoma cells and conducted comparative mass spectrometric analyses. 85 cellular proteins and three viral proteins were successfully identified in three independent trials, among which alphafetoprotein (AFP, UDP-glucose: glycoprotein glucosyltransferase 1 (UGT1 and HCV NS4B were further validated as novel E2 binding partners. Subsequent functional characterization demonstrated that gene silencing of UGT1 in human hepatoma cell line Huh7.5.1 markedly decreased the production of infectious HCV, indicating a regulatory role of UGT1 in viral lifecycle. Domain mapping experiments showed that HCV E2-NS4B interaction requires the transmembrane domains of the two proteins. Altogether, our proteomics study has uncovered key viral and cellular factors that interact with E2 and provided new insights into our understanding of HCV infection.

  13. Comparative Proteomics Reveals Important Viral-Host Interactions in HCV-Infected Human Liver Cells.

    Science.gov (United States)

    Liu, Shufeng; Zhao, Ting; Song, BenBen; Zhou, Jianhua; Wang, Tony T

    2016-01-01

    Hepatitis C virus (HCV) poses a global threat to public health. HCV envelop protein E2 is the major component on the virus envelope, which plays an important role in virus entry and morphogenesis. Here, for the first time, we affinity purified E2 complex formed in HCV-infected human hepatoma cells and conducted comparative mass spectrometric analyses. 85 cellular proteins and three viral proteins were successfully identified in three independent trials, among which alphafetoprotein (AFP), UDP-glucose: glycoprotein glucosyltransferase 1 (UGT1) and HCV NS4B were further validated as novel E2 binding partners. Subsequent functional characterization demonstrated that gene silencing of UGT1 in human hepatoma cell line Huh7.5.1 markedly decreased the production of infectious HCV, indicating a regulatory role of UGT1 in viral lifecycle. Domain mapping experiments showed that HCV E2-NS4B interaction requires the transmembrane domains of the two proteins. Altogether, our proteomics study has uncovered key viral and cellular factors that interact with E2 and provided new insights into our understanding of HCV infection. PMID:26808496

  14. HIV and HCV: from Co-infection to Epidemiology, Transmission,Pathogenesis, and Treatment

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Human immunodeficiency virus (HIV) is the infectious agent causing acquired immunodeficiency syndrome (AIDS), a deadliest scourge of human society. Hepatitis C virus (HCV) is a major causative agent of chronic liver disease and infects an estimated 170 million people worldwide,resulting in a serious public health burden. Due to shared routes of transmission, co-infection with HIV and HCV has become common among individuals who had high risks of blood exposures. Among hemophiliacs the co-infection rate accounts for 85%; while among injection drug users (IDU) the rate can be as high as 90%. HIV can accelerate the progression of HCV-related liver disease, particularly when immunodeficiency has developed. Although the effect of HCV on HIV infection is controversial,most studies showed an increase in mortality due to liver disease. HCV may act as a direct cofactor to fasten the progression of AIDS and decrease the tolerance of highly active antiretroviral therapy(HARRT). Conversely, HAART-related hepatotoxicity may enhance the progression of liver fibrosis.Due to above complications, co-infection with HCV and HIV-1 has imposed a critical challenge in the management of these patients. In this review, we focus on the epidemiology and transmission of HIV and HCV, the impact of the two viruses on each other, and their treatment.

  15. Nicht-invasive Fibrosegradbestimmung der Leber mittels FibroScan®, APRI und FIB-4-Index bei Lebertransplantierten aufgrund HCV- und äthyltoxischer Zirrhose

    OpenAIRE

    Lotz, Katharina Dorothee

    2010-01-01

    Chronic hepatitis C infection is the main reason for liver transplantation in Germany. Recurrent hepatitis C virus (HCV) infection after liver transplantation is a severe problem because it can lead to liver fibrosis and cirrhosis. Therefore an early detection of liver fibrosis is crucial. Currently liver biopsy is the gold-standard in assessing the stage of fibrosis in liver histology but it is limited by its invasiveness. In recent years several non-invasive tests for assessment of liver fi...

  16. HCV NS5A abrogates p53 protein function by interfering with p53-DNA binding

    Institute of Scientific and Technical Information of China (English)

    Guo-Zhong Gong; Yong-Fang Jiang; Yan He; Li-Ying Lai; Ying-Hua Zhu; Xian-Shi Su

    2004-01-01

    AIM: To evaluate the inhibition effect of HCV NS5A on p53 transactivation on p21 promoter and explore its possible mechanism for influencing p53 function.METHODS: p53 function of transactivation on p21 promoter was studied with a luciferase reporter system in which the luciferase gene is driven by p21 promoter, and the p53-DNA binding ability was observed with the use of electrophoretic mobility-shift assay (EMSA). Lipofectin mediated p53 or HCV NS5A expression vectors were used to transfect hepatoma cell lines to observe whether HCV NS5A could abrogate the binding ability of p53 to its specific DNA sequence and p53 transactivation on p21 promoter.Western blot experiment was used for detection of HCV NS5A and p53 proteins expression.RESULTS: Relative luciferase activity driven by p21 promoter increased significantly in the presence of endogenous p53 protein. Compared to the control group, exogenous p53 protein also stimulated p21 promoter driven luciferase gene expression in a dose-dependent way. HCV NS5A protein gradually inhibited both endogenous and exogenous p53 transactivation on p21 promoter with increase of the dose of HCV NS5A expression plasmid. By the experiment of EMSA, we could find p53 binding to its specific DNA sequence and, when co-transfected with increased dose of HCV NS5A expression vector, the p53 binding affinity to its DNA gradually decreased and finally disappeared. Between the Huh 7 cells transfected with p53 expression vector alone or co-transfected with HCV NS5A expression vector, there was no difference in the p53 protein expression.CONCLUSION: HCV NS5A inhibits p53 transactivation on p21 promoter through abrogating p53 binding affinity to its specific DNA sequence. It does not affect p53 protein expression.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Response rates of standard interferon therapy in chronic HCV patients of Khyber Pakhtunkhwa (KPK

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    Ahmad Bashir

    2012-01-01

    Full Text Available Abstract Background Interferon based therapy is used to eradicate the Hepatitis C Virus from the bodies of the infected individuals. HCV is highly prevalent in Khyber Pakhtunkhwa (KPK that is why it is important to determine the response of standard interferon based therapy in Chronic HCV patients of the region. Study design A total of 174 patients were selected for interferon based therapy. The patients were selected from four different regions of KPK. After confirmation of active HCV infection by Real Time PCR, standard interferon with ribavirn was given to patients for 6 months. After completion of therapy, end of treatment virologic response (ETR was calculated. Results Out of total 174 patients, 130 (74.71% showed ETR and 44 (25.28% did not show ETR. In district Bunir, out of 52 patients, 36 (69.23% showed ETR and 16 (30.79% did not show ETR. In district Mardan, out of the total 74 patients, 66 (89.18% were negative for HCV RNA and 8 (10.81% were resistant to therapy. In Peshawar, out of 22, 16 (60% were negative and 6 (40% were positive for HCV RNA at the end of 6 months therapy. In the Federally Administered Tribal Area (FATA, out of 18 only 10 (55.5% were negative and 8 (44.45% were positive for active HCV infection. Conclusion It is concluded that the response of antiviral therapy against HCV infection in chronic HCV patients of KPK province is 74.71%. The high response rate may be due to the prevalence of IFN-responsive HCV genotypes (2 and 3 in KPK.

  19. A candidate DNA vaccine elicits HCV specific humoral and cellular immune responses

    Institute of Scientific and Technical Information of China (English)

    Li-Xin Zhu; Jing Liu; Ye Ye; You-Hua Xie; Yu-Ying Kong; Guang-Di Li; Yuan Wang

    2004-01-01

    AIM: To investigate the immunogenicity of candidate DNA vaccine against hepatitis C virus (HCV) delivered by two plasmids expressing HCV envelope protein 1 (E1) and envelope protein 2 (E2) antigens respectively and to study the effect of CpG adjuvant on this candidate vaccine.METHODS: Recombinant plasmids expressing HCV E1 and E2 antigens respectively were used to simultaneously inoculate mice with or without CpG adjuvant. Antisera were then collected and titers of anti-HCV antibodies were analyzed by ELISA. One month after the last injection, animals were sacrificed to prepare single-cell suspension of splenocytes.These cells were subjected to HCVantigen specific proliferation assays and cytokine secretion assays to evaluate the cellular immune responses of the vaccinated animals.RESULTS: Antibody responses to HCV E1 and E2 antigens were detected in vaccinated animals. Animals receiving CpG adjuvant had slightly lower titers of anti-HCV antibodies in the sera, while the splenocytes from these animals showed higher HCV-antigen specific proliferation. Analysis of cytokine secretion from the splenocytes was consistent with the above results. While no antigen-specific IL-4 secretion was detected for all vaccinated animals, HCV antigen-specific INF-γ secretion was detected for the splenocytes of vaccinated animals. CpG adjuvant enhanced the secretion of INF-γ but did not change the profile of IL-4 secretion.CONCLUSION: Vaccination of mice with plasmids encoding HCV E1 and E2 antigens induces humoral and cellular immune responses. CpG adjuvant significantly enhances the cellular immune response.

  20. 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.

  1. 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

    International Nuclear Information System (INIS)

    Highlights: → HCV infection upregulated miR-192, -194, -215, downregulated miR-320, -491. → Transfection of miR-192, -215, and -491 enhanced HCV replication. → Transfection of miR-491 inhibited Akt phosphorylation. → 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.

  2. HIV and Hepatitis C Virus Testing and Seropositivity Rates in Canadian Federal Penitentiaries: A Critical Opportunity for Care and Prevention

    OpenAIRE

    Prithwish De; Nancy Connor; Françoise Bouchard; Donald Sutherland

    2004-01-01

    BACKGROUND: Incarcerated persons experience high rates of HIV and hepatitis C virus (HCV) infection, but little is known about the burden of these bloodborne viruses among federal penitentiary inmates in Canada.OBJECTIVES: The present study investigates rates of testing and seropositivity for HIV and HCV among inmates in all 53 Canadian federal penitentiaries.METHODS: A cross-sectional design using surveillance data on voluntary HIV and HCV antibody testing in 2002 were applied to estimate th...

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

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    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.

  4. Measurement of HCV-Specific CD8(+) Cytotoxic T-Cell Activities in the Peripheral Blood by Europium Release Assay.

    Science.gov (United States)

    Imawari, M

    1999-01-01

    Peripheral blood mononuclear cells (PBMC) contain NK cells, cytotoxic T-lymphocytes (CTL), helper T-cells, and B-cells that respond to viral infection and act to eliminate the virus from infected individuals. CTLs are not only thought to be a major host defense against viral infection, but are also implicated in the immunopathogenesis. Classical CTLs are CD8(+) and recognize endogenously synthesized and processed antigen in association with a human leukocyte antigen (HLA) class I molecule. The antigens are usually 8-10 amino acids long. HCV-specific CTLs have been demonstrated in the peripheral blood of some of patients with HCV infection by stimulating PBMC with the HCV synthetic peptides (1). The peptides were synthesized as overlapping peptides to encompass a certain region of the HCV antigen (1), on the basis of antigenicity prediction from the amino acid composition of HCV (2), or on the basis of the HLA binding motifs in the HCV antigen (3). Several minimal and optimal epitopes in the HCV antigen and their HLA restriction of recognition by CTLs have been defined. Recently, it has been reported that HCV-specific CTLs may suppress the outgrowth of HCV (4). In this chapter, methods will be discussed that demonstrate HCV-specific CTLs in the peripheral blood of patients with HCV infection. We use nonradioisotope europium (Eu) for assay of CTL activities. PMID:21374383

  5. Exposure to low infective doses of HCV induces cellular immune responses without consistently detectable viremia or seroconversion in chimpanzees

    International Nuclear Information System (INIS)

    In hepatitis C virus (HCV) infection, there is accumulating data suggesting the presence of cellular immune responses to HCV in exposed but seemingly uninfected populations. Some studies have suggested cross-reactive antigens rather than prior HCV exposure as the main reason for the immune responses. In this study we address this question by analyzing the immune response of chimpanzees that have been sequentially exposed to increasing doses of HCV virions. The level of viremia, as well as the immune responses to HCV at different times after virus inoculation, were examined. Our data indicate that HCV infective doses as low as 1-10 RNA (+) virions induce detectable cellular immune responses in chimpanzees without consistently detectable viremia or persistent seroconversion. However, increasing the infective doses of HCV to 100 RNA (+) virions overcame the low-inoculum-induced immune response and produced high-level viremia followed by seroconversion

  6. Clonal expansion of immunoglobulin M+CD27+ B cells in HCV-associated mixed cryoglobulinemia

    OpenAIRE

    Charles, Edgar D.; Green, Rashidah M.; Marukian, Svetlana; Talal, Andrew H.; Lake-Bakaar, Gerond V.; Jacobson, Ira M.; Rice, Charles M.; Dustin, Lynn B.

    2008-01-01

    Hepatitis C virus (HCV) is associated with B-cell lymphoproliferative disorders such as mixed cryoglobulinemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). The pathogenesis of these disorders remains unclear, and it has been proposed that HCV drives the pro-liferation of B cells. Here we demonstrate that certain HCV+MC+ subjects have clonal expansions of immunoglobulin M (IgM)+κ+IgDlow/−CD21lowCD27+ B cells. Using RT-PCR to amplify Ig from these singly sorted cells, we show that these predom...

  7. NS4A protein as a marker of HCV history suggests that different HCV genotypes originally evolved from genotype 1b

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    Asad Sultan

    2011-06-01

    Full Text Available Abstract Background The 9.6 kb long RNA genome of Hepatitis C virus (HCV is under the control of RNA dependent RNA polymerase, an error-prone enzyme, for its transcription and replication. A high rate of mutation has been found to be associated with RNA viruses like HCV. Based on genetic variability, HCV has been classified into 6 different major genotypes and 11 different subtypes. However this classification system does not provide significant information about the origin of the virus, primarily due to high mutation rate at nucleotide level. HCV genome codes for a single polyprotein of about 3011 amino acids which is processed into structural and non-structural proteins inside host cell by viral and cellular proteases. Results We have identified a conserved NS4A protein sequence for HCV genotype 3a reported from four different continents of the world i.e. Europe, America, Australia and Asia. We investigated 346 sequences and compared amino acid composition of NS4A protein of different HCV genotypes through Multiple Sequence Alignment and observed amino acid substitutions C22, V29, V30, V38, Q46 and Q47 in NS4A protein of genotype 1b. Furthermore, we observed C22 and V30 as more consistent members of NS4A protein of genotype 1a. Similarly Q46 and Q47 in genotype 5, V29, V30, Q46 and Q47 in genotype 4, C22, Q46 and Q47 in genotype 6, C22, V38, Q46 and Q47 in genotype 3 and C22 in genotype 2 as more consistent members of NS4A protein of these genotypes. So the different amino acids that were introduced as substitutions in NS4A protein of genotype 1 subtype 1b have been retained as consistent members of the NS4A protein of other known genotypes. Conclusion These observations indicate that NS4A protein of different HCV genotypes originally evolved from NS4A protein of genotype 1 subtype 1b, which in turn indicate that HCV genotype 1 subtype 1b established itself earlier in human population and all other known genotypes evolved later as a result of

  8. Guidelines for laboratory testing and result reporting of antibody to hepatitis C virus. Centers for Disease Control and Prevention.

    Science.gov (United States)

    Alter, Miriam J; Kuhnert, Wendi L; Finelli, Lyn

    2003-02-01

    Testing for the presence of antibody to hepatitis C virus (anti-HCV) is recommended for initially identifying persons with hepatitis C virus (HCV) infection (CDC. Recommendations for prevention and control of hepatitis C virus [HCV] infection and HCV-related chronic disease. MMWR 1998;47[No. RR-19] :1-33). Testing for anti-HCV should include use of an antibody screening assay, and for screening test-positive results, a more specific supplemental assay. Verifying the presence of anti-HCV minimizes unnecessary medical visits and psychological harm for persons who test falsely positive by screening assays and ensures that counseling, medical referral, and evaluation are targeted for patients serologically confirmed as having been infected with HCV. However, substantial variation in reflex supplemental testing practices exists among laboratories, and an anti-HCV-positive laboratory report does not uniformly represent a confirmed positive result. These guidelines expand recommendations for anti-HCV testing to include an option for reflex supplemental testing based on screening-test-positive signal-to-cut-off (s/co) ratios. Use of s/co ratios minimizes the amount of supplemental testing that needs to be performed while improving the reliability of reported test results. These guidelines were developed on the basis of available knowledge of CDC staff in consultation with representatives from the Food and Drug Administration and public health, hospital, and independent laboratories. Adoption of these guidelines by all public and private laboratories that perform in vitro diagnostic anti-HCV testing will improve the accuracy and utility of reported anti-HCV test results for counseling and medical evaluation of patients by health-care professionals and for surveillance by public health departments. PMID:12585742

  9. Seroprevalence of Hepatitis C (HCV and Human Immunodeficiency Virus (HIV infection among street children in Isfahan, Iran

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    Ataei B

    2010-02-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: There are millions of children around the world living on the street. They are at higher risk of physical, sexual and drug abuse, and have no access to health care facilities. Therefore they are at risk of viral infections such as HCV and HIV. The aim of this study was determining the prevalence of HCV and HIV infection in Isfahan street children (2005-2007."n"nMethods: The cross-sectional study was taken place on 386 street children through a nonprobable-convenience sampling method. They were requested to answer a questionnaire (demographic and behavioral data, and then they were tested for anti HCV and anti HIV antibodies."n"nResults: Among 386 street children, 270 (70% were boys and the mean age was 12.62±3.23 years. The majority of them, 267 cases (69%, were on the street for financial reasons. 353 (91.7%, 366 (94.8% and 375 (97.2% of them had no history of smoking, using alcohol or substance addiction, respectively. 40 (34.5% of girls and 12 (4.4% of boys (p<0.0001 were engaged in sex and 79 (68% of girls and 46 (17% of boys (p<0.0001 were involved in physical fighting. All of the children had negative serology for HIV infection. Nevertheless, four of them (1% were positive for HCV Ab

  10. Anti-HCV RNA Aptamers Targeting the Genomic cis-Acting Replication Element

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    Alfredo Berzal-Herranz

    2011-12-01

    Full Text Available Hepatitis C virus (HCV replication is dependent on the existence of several highly conserved functional genomic RNA domains. The cis-acting replication element (CRE, located within the 3' end of the NS5B coding region of the HCV genome, has been shown essential for efficient viral replication. Its sequence and structural features determine its involvement in functional interactions with viral RNA-dependent RNA polymerase and distant RNA domains of the viral genome. This work reports the use of an in vitro selection strategy to select aptamer RNA molecules against the complete HCV-CRE. After six selection cycles, five potential target sites were identified within this domain. Inhibition assays using a sample of representative aptamers showed that the selected RNAs significantly inhibit the replication (>80% of a subgenomic HCV replicon in Huh-7 cell cultures. These results highlight the potential of aptamer RNA molecules as therapeutic antiviral agents.

  11. New developments in small molecular compounds for anti-hepatitis C virus (HCV) therapy

    Institute of Scientific and Technical Information of China (English)

    Jing TONG; You-wei WANG; Yuan-an LU

    2012-01-01

    Infection with hepatitis C virus (HCV) affects approximately 170 million people worldwide.However,no vaccine or immunoglobulin is currently available for the prevention of HCV infection.The standard of care (SOC)involving pegylated intenrferon-α (PEG-IFN α) plus ribavirin (RBV) for 48 weeks results in a sustained virologic response in less than 50% of patients with chronic hepatitis C genotype 1,the most prevalent type of HCV in North America and Europe.Recently,reliable in vitro culture systems have been developed for accelerating antiviral therapy research,and many new specifically targeted antiviral therapies for hepatitis C (STAT-C) and treatment strategies are being evaluated in clinical trials.These new antiviral agents are expected to improve present treatment significantly and may potentially shorten treatment duration.The aim of this review is to summarize the current developments in new anti-HCV drugs.

  12. 77 FR 30293 - Recommendations for the Identification of Hepatitis C Virus (HCV) Chronic Infection

    Science.gov (United States)

    2012-05-22

    ... chronic infection, which places infected persons at risk for liver cirrhosis, liver cancer or...-viral therapies can clear HCV from the system (i.e., a virologic cure) and halt disease progression...

  13. Correlations of folic acid, vitamin B12, homocysteine, and thrombopoietin to platelet count in HCV infection

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    Somayh S. Eissa

    2012-01-01

    Conclusion This study concluded that TCP in HCV-related chronic liver diseases is multifactorial and decreased FA is involved in its pathogenesis as an independent risk factor. Increased Hcy may cause TCP through platelet activation and endothelial dysfunction.

  14. Microarray analysis identifies a common set of cellular genes modulated by different HCV replicon clones

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    Gerosolimo Germano

    2008-06-01

    Full Text Available Abstract Background Hepatitis C virus (HCV RNA synthesis and protein expression affect cell homeostasis by modulation of gene expression. The impact of HCV replication on global cell transcription has not been fully evaluated. Thus, we analysed the expression profiles of different clones of human hepatoma-derived Huh-7 cells carrying a self-replicating HCV RNA which express all viral proteins (HCV replicon system. Results First, we compared the expression profile of HCV replicon clone 21-5 with both the Huh-7 parental cells and the 21-5 cured (21-5c cells. In these latter, the HCV RNA has been eliminated by IFN-α treatment. To confirm data, we also analyzed microarray results from both the 21-5 and two other HCV replicon clones, 22-6 and 21-7, compared to the Huh-7 cells. The study was carried out by using the Applied Biosystems (AB Human Genome Survey Microarray v1.0 which provides 31,700 probes that correspond to 27,868 human genes. Microarray analysis revealed a specific transcriptional program induced by HCV in replicon cells respect to both IFN-α-cured and Huh-7 cells. From the original datasets of differentially expressed genes, we selected by Venn diagrams a final list of 38 genes modulated by HCV in all clones. Most of the 38 genes have never been described before and showed high fold-change associated with significant p-value, strongly supporting data reliability. Classification of the 38 genes by Panther System identified functional categories that were significantly enriched in this gene set, such as histones and ribosomal proteins as well as extracellular matrix and intracellular protein traffic. The dataset also included new genes involved in lipid metabolism, extracellular matrix and cytoskeletal network, which may be critical for HCV replication and pathogenesis. Conclusion Our data provide a comprehensive analysis of alterations in gene expression induced by HCV replication and reveal modulation of new genes potentially useful

  15. Temporal changes in HCV genotype distribution in three different high risk populations in San Francisco, California

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    Evans Jennifer

    2011-08-01

    Full Text Available Abstract Background Hepatitis C virus (HCV genotype (GT has become an important measure in the diagnosis and monitoring of HCV infection treatment. In the United States (U.S. HCV GT 1 is reported as the most common infecting GT among chronically infected patients. In Europe, however, recent studies have suggested that the epidemiology of HCV GTs is changing. Methods We assessed HCV GT distribution in 460 patients from three HCV-infected high risk populations in San Francisco, and examined patterns by birth cohort to assess temporal trends. Multiple logistic regression was used to assess factors independently associated with GT 1 infection compared to other GTs (2, 3, and 4. Results Overall, GT 1 was predominant (72.4%, however younger injection drug users (IDU had a lower proportion of GT 1 infections (54.7% compared to older IDU and HIV-infected patients (80.5% and 76.6%, respectively. Analysis by birth cohort showed increasing proportions of non-GT 1 infections associated with year of birth: birth before 1970 was independently associated with higher adjusted odds of GT 1: AOR 2.03 (95% CI: 1.23, 3.34. African-Americans as compared to whites also had higher adjusted odds of GT 1 infection (AOR: 3.37; 95% CI: 1.89, 5.99. Conclusions Although, HCV GT 1 remains the most prevalent GT, especially among older groups, changes in GT distribution could have significant implications for how HCV might be controlled on a population level and treated on an individual level.

  16. Screening compounds against HCV based on MAVS/IFN-β pathway in a replicon mode

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To develop a sensitive assay for screening compounds against hepatitis C virus (HCV).METHODS:The proteolytic cleavage of NS3/4A on enhanced yellow fluorescent protein (eYFP)-mitochondrial antiviral signaling protein (MAVS) was examined by reporter enzyme secreted placental alkaline phosphatase (SEAP),which enabled us to perform ongoing monitoring of anti-HCV drugs through repeated chemiluminescence.Subcellular localization of eYFP-MAVS was assessed by fluorescence microscopy.Cellular localization and pr...

  17. HVR1-mediated antibody evasion of highly infectious in vivo adapted HCV in humanised mice

    DEFF Research Database (Denmark)

    Prentoe, Jannick; Verhoye, Lieven; Velázquez Moctezuma, Rodrigo;

    2016-01-01

    OBJECTIVE: HCV is a major cause of chronic liver disease worldwide, but the role of neutralising antibodies (nAbs) in its natural history remains poorly defined. We analysed the in vivo role of hypervariable region 1 (HVR1) for HCV virion properties, including nAb susceptibility. DESIGN: Analysis...... using HVR1-deleted viruses as vaccine antigens to boost broadly reactive protective nAb responses....

  18. Studies on the allostimulatory function of dendritic cells from HCV-HIV-1 co-infected patients

    Institute of Scientific and Technical Information of China (English)

    Justin STEBBING; Brian GAZZARD; Steve PATTERSON; Simon PORTSMOUTH; Claire THOMAS; Robert GLASSMAN; Adrian WILDFIRE; Frances GOTCH; Mark BOWER; Mark NELSON

    2004-01-01

    There is increasing recognition of the potential morbidity and mortality associated with HIV-1 and hepatitis C (HCV)co-infection. HIV appears to adversely affect HCV disease while the reciprocal effect of HCV on HIV remains controversial.We therefore studied the effect of co-infection on dendritic cell function versus HIV infection alone, as previous work has shown that HCV impairs dendritic cell (DC) function. HIV-1 positive individuals with HCV were matched for CD4count, HIV- 1 RNA viral load and therapy, to HIV- 1 positive patients without HCV. Monocyte-derived DC were generated and mixed leukocyte reactions were performed. We assessed allostimulatory capacity with and without administration of exogenous Thl cytokines, using thymidine uptake and cell division analyses with the vital dye CFSE. We found that monocyte-derived DC from co-infected individuals showed no significant differences in allostimulatory capacity to ex vivo generated DC from HIV-1 infected individuals without HCV. Unlike the situation with HCV infection alone, this impairment was not reversed by increasing concentrations of either interleukin-2 or -12. Monocyte-derived DC from HIV-1 and HCV co-infected individuals have a similar allostimulatory capacity to DC from matched patients with HIV-1alone. These findings are compatible with results of prior clinical studies that found no evidence that HCV co-infection altered HIV disease progression and has implications for immunotherapeutic approaches in co-infected individuals.

  19. Hepatitis B virus reactivation after treatment for hepatitis C in hemodialysis patients with HBV/HCV coinfection

    Directory of Open Access Journals (Sweden)

    Raul Carlos Wahle

    2015-10-01

    Full Text Available ABSTRACTIn coinfected HBV/HCV patients, HBV replication is usually suppressed by HCV over the time. No study to date has evaluated the HBV viremia in long-term follow-up after HCV treatment in hemodialysis patients with HBV/HCV coinfection. This study aimed to assess the evolution of HBV viremia after HCV treatment in this special population. Ten hemodialysis patients with HBV/HCV coinfection with dominant HCV infection (HBV lower than 2000 IU/mL and significant fibrosis were treated with interferon-alpha 3 MU 3×/week for 12 months and could be followed for at least 36 months after HCV treatment. Six cases of HBV reactivation (60% during follow-up were observed and 5/6 had been successfully treated for HCV. Patients with HBV reactivation received anti-HBV therapy. Our preliminary findings indicate that treatment of hepatitis C in HBV/HCV coinfected hemodialysis patients may favor HBV reactivation. Thus, continued monitoring of HBV viremia must be recommended and prompt anti-HBV therapy should be implemented.

  20. Liver histology in co-infection of hepatitis C virus (HCV and Hepatitis G virus (HGV

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    STRAUSS Edna

    2002-01-01

    Full Text Available As little is known about liver histology in the co-infection of hepatitis C virus (HCV and hepatitis G virus (HGV, HGV RNA was investigated in 46 blood donors with hepatitis C, 22 of them with liver biopsy: co-infection HCV / HGV (n = 6 and HCV isolated infection (n = 16. Besides staging and grading of inflammation at portal, peri-portal and lobular areas (Brazilian Consensus, the fibrosis progression index was also calculated. All patients had no symptoms or signs of liver disease and prevalence of HGV / HCV co-infection was 15.2%. Most patients had mild liver disease and fibrosis progression index, calculated only in patients with known duration of infection, was 0.110 for co-infection and 0.130 for isolated HCV infection, characterizing these patients as "slow fibrosers". No statistical differences could be found between the groups, although a lesser degree of inflammation was always present in co-infection. In conclusion co-infection HCV / HGV does not induce a more aggressive liver disease, supporting the hypothesis that HGV is not pathogenic.

  1. A New Twist to a Chronic HCV Infection: Occult Hepatitis C

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    Bashar M. Attar

    2015-01-01

    Full Text Available Background. The prevalence of occult hepatitis C infection (OCI in the population of HCV-RNA negative but anti-HCV positive individuals is presently unknown. OCI may be responsible for clinically overt recurrent disease following an apparent sustained viral response (SVR weeks to years later. Purpose. To review the available current literature regarding OCI, prevalence, pathogenic mechanisms, clinical characteristics, and future directions. Data Sources. Searching MEDLINE, article references, and national and international meeting abstracts for the diagnosis of OCI (1990–2014. Data Synthesis. The long-term followup of individuals with an OCI suggests that the infection can be transient with the loss of detectable HCV-RNA in PPBMCs after 12–18 months or alternatively exist intermittently and potentially long term. The ultimate outcome of HCV infection is decided by interplay between host immune responses, antiviral therapies, and the various well-identified viral evasion mechanisms as well as the presence of HCV infection within extrahepatic tissues. Conclusion. The currently widely held assumption of a HCV-cure in individuals having had “SVR” after 8–12 weeks of a course of DAA therapy as recently defined may not be entirely valid. Careful longitudinal followup utilizing highly sensitive assays and unique approaches to viral isolation are needed.

  2. Biological properties of purified recombinant HCV particles with an epitope-tagged envelope

    International Nuclear Information System (INIS)

    To establish a simple system for purification of recombinant infectious hepatitis C virus (HCV) particles, we designed a chimeric J6/JFH-1 virus with a FLAG (FL)-epitope-tagged sequence at the N-terminal region of the E2 hypervariable region-1 (HVR1) gene (J6/JFH-1/1FL). We found that introduction of an adaptive mutation at the potential N-glycosylation site (E2N151K) leads to efficient production of the chimeric virus. This finding suggests the involvement of glycosylation at Asn within the envelope protein(s) in HCV morphogenesis. To further analyze the biological properties of the purified recombinant HCV particles, we developed a strategy for large-scale production and purification of recombinant J6/JFH-1/1FL/E2N151K. Infectious particles were purified from the culture medium of J6/JFH-1/1FL/E2N151K-infected Huh-7 cells using anti-FLAG affinity chromatography in combination with ultrafiltration. Electron microscopy of the purified particles using negative staining showed spherical particle structures with a diameter of 40-60 nm and spike-like projections. Purified HCV particle-immunization induced both an anti-E2 and an anti-FLAG antibody response in immunized mice. This strategy may contribute to future detailed analysis of HCV particle structure and to HCV vaccine development.

  3. Biological properties of purified recombinant HCV particles with an epitope-tagged envelope

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Hitoshi; Akazawa, Daisuke [Department of Virology II, National Institute of Infectious Diseases, Tokyo (Japan); Toray Industries, Inc., Kanagawa (Japan); Kato, Takanobu; Date, Tomoko [Department of Virology II, National Institute of Infectious Diseases, Tokyo (Japan); Shirakura, Masayuki [Department of Virology II, National Institute of Infectious Diseases, Tokyo (Japan); Toray Industries, Inc., Kanagawa (Japan); Nakamura, Noriko; Mochizuki, Hidenori [Toray Industries, Inc., Kanagawa (Japan); Tanaka-Kaneko, Keiko; Sata, Tetsutaro [Department of Pathology, National Institute of Infectious Diseases, Tokyo (Japan); Tanaka, Yasuhito [Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medicine, Nagoya (Japan); Mizokami, Masashi [Research Center for Hepatitis and Immunology, Kohnodai Hospital, International Medical Center of Japan, Chiba (Japan); Suzuki, Tetsuro [Department of Virology II, National Institute of Infectious Diseases, Tokyo (Japan); Wakita, Takaji, E-mail: wakita@nih.go.jp [Department of Virology II, National Institute of Infectious Diseases, Tokyo (Japan)

    2010-05-14

    To establish a simple system for purification of recombinant infectious hepatitis C virus (HCV) particles, we designed a chimeric J6/JFH-1 virus with a FLAG (FL)-epitope-tagged sequence at the N-terminal region of the E2 hypervariable region-1 (HVR1) gene (J6/JFH-1/1FL). We found that introduction of an adaptive mutation at the potential N-glycosylation site (E2N151K) leads to efficient production of the chimeric virus. This finding suggests the involvement of glycosylation at Asn within the envelope protein(s) in HCV morphogenesis. To further analyze the biological properties of the purified recombinant HCV particles, we developed a strategy for large-scale production and purification of recombinant J6/JFH-1/1FL/E2N151K. Infectious particles were purified from the culture medium of J6/JFH-1/1FL/E2N151K-infected Huh-7 cells using anti-FLAG affinity chromatography in combination with ultrafiltration. Electron microscopy of the purified particles using negative staining showed spherical particle structures with a diameter of 40-60 nm and spike-like projections. Purified HCV particle-immunization induced both an anti-E2 and an anti-FLAG antibody response in immunized mice. This strategy may contribute to future detailed analysis of HCV particle structure and to HCV vaccine development.

  4. A Unique Pattern of HCV Genotype Distribution on Hainan Island in China Revealed by Evolutionary Analysis

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    Tao Wu

    2016-06-01

    Full Text Available Background/Aims: Different genotypes of HCV may differ in both disease progression and response to antiviral therapies. Hainan Island has been inhabited by the “Li” aboriginal minority for centuries. We aimed to provide a better understanding of HCV infection on Hainan Island, so that the information would help improve strategies for HCV prevention and control on the island and in the wider country. Methods: Using RT-PCR and DNA sequencing, we determined HCV sequences from 100 patients living on Hainan Island. Results: Phylogenetic analysis classified these sequences into six subtypes: 6a (n=35, 1b (n=31, 3b (n=16, 2a (n=8, 3a (n=6, and 1a (n=4. By including reference sequences reported from elsewhere in China, phylogeographic trees were reconstructed to indicate their migration patterns. While the predominant 6a isolates were estimated to have origins in Guangdong and Guangxi provinces, the increase in 3b strains must have resulted from IDU network transmission from the southwest. A Bayesian Skyline Plot for subtype 1a, which is rare in China, showed a rapid population growth since 1998. Although slowed in rate around 2005, this growth continued to the present. Not found for any other HCV lineage. Conclusions: Overall, a delayed growth pattern may indicate the unique history of 1a dissemination in China and its recently increasing prevalence, despite measures taken to improve HCV prevention.

  5. Classification of HCV NS5B Polymerase Inhibitors Using Support Vector Machine

    Directory of Open Access Journals (Sweden)

    Changyuan Yu

    2012-03-01

    Full Text Available Using a support vector machine (SVM, three classification models were built to predict whether a compound is an active or weakly active inhibitor based on a dataset of 386 hepatitis C virus (HCV NS5B polymerase NNIs (non-nucleoside analogue inhibitors fitting into the pocket of the NNI III binding site. For each molecule, global descriptors, 2D and 3D property autocorrelation descriptors were calculated from the program ADRIANA.Code. Three models were developed with the combination of different types of descriptors. Model 2 based on 16 global and 2D autocorrelation descriptors gave the highest prediction accuracy of 88.24% and MCC (Matthews correlation coefficient of 0.789 on test set. Model 1 based on 13 global descriptors showed the highest prediction accuracy of 86.25% and MCC of 0.732 on external test set (including 80 compounds. Some molecular properties such as molecular shape descriptors (InertiaZ, InertiaX and Span, number of rotatable bonds (NRotBond, water solubility (LogS, and hydrogen bonding related descriptors performed important roles in the interactions between the ligand and NS5B polymerase.

  6. Synthesis and Characterization of Celecoxib Derivatives as Possible Anti-Inflammatory, Analgesic, Antioxidant, Anticancer and Anti-HCV Agents

    Directory of Open Access Journals (Sweden)

    Amartya Basu

    2013-03-01

    Full Text Available A series of novel N-(3-substituted aryl/alkyl-4-oxo-1,3-thiazolidin-2-ylidene-4-[5-(4-methylphenyl-3-(trifluoromethyl-1H-pyrazol-1-yl]benzenesulfonamides 2a–e were synthesized by the addition of ethyl a-bromoacetate and anhydrous sodium acetate in dry ethanol to N-(substituted aryl/alkylcarbamothioyl-4-[5-(4-methylphenyl-3-(trifluoro-methyl-1H-pyrazol-1-yl]benzene sulfonamides 1a–e, which were synthesized by the reaction of alkyl/aryl isothiocyanates with celecoxib. The structures of the isolated products were determined by spectral methods and their anti-inflammatory, analgesic, antioxidant, anticancer and anti-HCV NS5B RNA-dependent RNA polymerase (RdRp activities evaluated. The compounds were also tested for gastric toxicity and selected compound 1a was screened for its anticancer activity against 60 human tumor cell lines. These investigations revealed that compound 1a exhibited anti-inflammatory and analgesic activities and further did not cause tissue damage in liver, kidney, colon and brain compared to untreated controls or celecoxib. Compounds 1c and 1d displayed modest inhibition of HCV NS5B RdRp activity. In conclusion, N-(ethylcarbamothioyl-4-[5-(4-methylphenyl-3-(trifluoromethyl-1H-pyrazol-1-yl]benzenesulfonamide (1a may have the potential to be developed into a therapeutic agent.

  7. Current Possibilities to Assess the Degree of Liver Fibrosis in Patients with Haemophilia Infected with HCV--Review.

    Science.gov (United States)

    Kucharska, Marta; Inglot, Marcin; Kuliszkiewicz-Janus, Małgorzata; Pazgan-Simon, Monika; Knysz, Brygida

    2015-01-01

    Haemophilia is an entity, wherein the HCV infection rate is greater than in the general population and ranges between 70-90%. The majority of HCV infections were acquired by hemophiliacs in the 1980s, by the use of infected cryoprecipitate or fresh frozen plasma preparations. It is therefore highly likely that many of them, more than twenty years after the infection, have developed advanced liver disease. Until recently, in order to assess its severity, it was necessary to perform a liver biopsy. Currently, we observe rapid developments of non-invasive methods that are particularly useful in patients with bleeding disorders. The most popular include elastography (Fibroscan, SWE) and the algorithms based on measurements of the relevant blood parameters (e.g. FibroTest, Fibrometer, APRI index). Ease of implementation of these studies, no need for hospitalization of the patient or specific preparation for surgery, allow for quick and minimally invasive assessment of liver disease progression and classification of the patient to the appropriate antiviral therapy. PMID:26469113

  8. Management of Antiviral Induced Anemia in HCV Infected Patients

    Directory of Open Access Journals (Sweden)

    Mitra Ranjbar

    2005-03-01

    Full Text Available IntroductionHepatitis C virus (HCV infection affects more than 170 million people worldwide(1,2. Approximately 80% of patients with acute infection will subsequently develop chronic disease, and an estimated 20% to 30% will develop cirrhosis and hepatocellular carcinoma(3. The maost effective therapeutic regimen for chronic hepatitis C is the combination of pegylated interferon alpha and ribavirin, which yields a sustained virologic response (SVR in up to 56% of patients(4, 5. However, combination therapy is also associated with significant adverse events and is contraindicated in certain patient populations. Development of side effects, particularly hematologic ones, may result in suboptimal dosing or discontinuation of therapy that can reduce the likelihood of SVR.IncidenceIn clinical trials, significant anemia (hemoglobin 10.6 mg/kg/d is 65% compared with a rate of 50% for those receiving peginterferon alfa-2b plus ribavirin at dosages of 10.6 mg/kg/d or less.It has been shown that SVR rates are significantly higher in patients who receive more than 80% of their full interferon alfa-2b plus ribavirin doses for more than 80% of the time for more than 80% of the intended duration of therapy(14. In the Hepatitis C Long-term Treatment Against Cirrhosis (HALT-C trial, a trial involving patients who were previous nonresponders to or relapsers after therapy, reduction of ribavirin dose from> 80% to 10.6 mg/kg/d. The standard-of-care management of ribavirin induced anemia has been dose reduction to 600 mg/d when the hemoglobin level decreases to =2g/dL decrease inhemoglobinduring any 4-weektreatment period 12g/dL despite 4weeks at reduceddose Recombinant human erythropoietin therapy in the HCV-infected patient who becomes anemic during antiviral therapy represents an alternative to ribavirin dose reduction or discontinuation. Erythropoietin is mainly produced by the kidney in adults in response to tissue hypoxia, and it increases the number of

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

    Directory of Open Access Journals (Sweden)

    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.

  10. HCV 5′NCR调控抑制活性的反义寡核苷酸的筛选%Specific regulatory inhibition of transfected HepG2 with HCV 5'NCR by antisense phosphorothioate oligodeoxynucleotides

    Institute of Scientific and Technical Information of China (English)

    王升启; 管伟; 王小红; 李梦东

    2000-01-01

    目的:寻找高效特异的新型抗HCV药物, 探讨针对HCV基因的硫代修饰反义寡核甘酸(S-ASODNs)最佳作用靶序列。 方法:参考HCV 5′NCR计算机预测的二级结构图,设计合成了15条S-ASODN、3条正义寡核苷酸及1条随机序列,采用HCV 5′NCR调控荧光素酶基因的瞬时表达系统,将S-ASODN与pHCV-neo4共转染,通过荧光素酶活性表达高低,反映S-ASODN对HCV调控基因的抑制活性。结果:5条S-ASODN即HCV65、HCV279、HCV363、HCV349及HCV352在25~100nmol/L浓度范围内,对HCV调控基因具有特异性的剂量依赖性抑制活性。当浓度为100nmol/L时,这些ASODN的抑制率可达80%以上,IC50值提示HCV363的抑制活性最强。通过阴性对照实验包括正义寡核苷酸、随机序列及不含HCV序列的靶载体pGL3提示ASODN仅存在轻度非特异性作用。此外,实验结果还提示不同作用靶位的ASODN之间具有一定的协同作用。 结论:HCV 5′NCR第二茎环结构Ⅱa、第三茎环结构Ⅲd和翻译起始区可能是ASODN作用的重要靶序列。%Objective: To screen efficient and specific new drugs against hepatitis C virus (HCV) and find the best target sequence of antisense oligodeoxynucleotides (ASODNs) targeting at HCV gene. Methods: Fifteen S-ASODNs targeting at the 5'NCR and start AUG of HCV RNA were designed and synthesized according to the predicted RNA secondary structure of the HCV 5'NCR and the adjacent AUG region. HepG2 cells were co-transfected with pHCV-neo4 and S-ASODN. The inhibitory effects of S-ASODNs on gene expression controlled by HCV 5'NCR were determined by the assay of luciferase activity. Results: Five S-ASODNs, i.e. HCV65, HCV279, HCV363, HCV349 and HCV352, showed sequence-specific and dose-dependent inhibitory activities with an inhibition rate of more than 80% at a concentration of 100 nmol/L. According to 50% inhibitory concentrations, the inhibitory activity of HCV363 was the best. On the

  11. Prevalence of hepatitis C virus among users attending a voluntary testing centre in Rio Grande, southern Brazil: predictive factors and hepatitis C virus genotypes.

    Science.gov (United States)

    Germano, F N; dos Santos, C A; Honscha, G; Strasburg, A; Gabbi, B; Mendoza-Sassi, R A; Soares, E A; Seuánez, H N; Soares, M A; Martínez, A M B

    2010-07-01

    We estimated the prevalence of hepatitis C (HCV) infection and associated risk factors in 750 individuals attending the Voluntary Counseling and Testing Center of Rio Grande (VCT/RG), in Southern Brazil, and identified viral genotypes. Demographic data and risk factors for HCV transmission were also collected and analysed. Anti-HCV antibody-positive individuals were tested for HCV-RNA and genotyped by sequencing the 5' untranslated region of the viral genome. Prevalence estimates of anti-HCV and HCV-RNA were 6% and 5.5%, respectively. We identified genotypes 1 (67%), 2 (2%) and 3 (31%); the latter was more prevalent than in other regions of Brazil. Anti-HCV prevalence in VCT/RG users was similar to previous reports. Age, previous blood transfusion, sexual orientation and injecting drug use were independent predictors of HCV infection. The presence of multiple risk factors was also associated with a higher risk for HCV infection. HCV genotype was not associated with any variable analysed in this study. PMID:20852195

  12. Chimeric antigen receptor (CAR)-engineered T cells redirected against hepatitis C virus (HCV) E2 glycoprotein

    Science.gov (United States)

    Sautto, Giuseppe A; Wisskirchen, Karin; Clementi, Nicola; Castelli, Matteo; Diotti, Roberta A; Graf, Julia; Clementi, Massimo; Burioni, Roberto; Protzer, Ulrike; Mancini, Nicasio

    2016-01-01

    Objective The recent availability of novel antiviral drugs has raised new hope for a more effective treatment of hepatitis C virus (HCV) infection and its severe sequelae. However, in the case of non-responding or relapsing patients, alternative strategies are needed. To this end we have used chimeric antigen receptors (CARs), a very promising approach recently used in several clinical trials to redirect primary human T cells against different tumours. In particular, we designed the first CARs against HCV targeting the HCV/E2 glycoprotein (HCV/E2). Design Anti-HCV/E2 CARs were composed of single-chain variable fragments (scFvs) obtained from a broadly cross-reactive and cross-neutralising human monoclonal antibody (mAb), e137, fused to the intracellular signalling motif of the costimulatory CD28 molecule and the CD3ζ domain. Activity of CAR-grafted T cells was evaluated in vitro against HCV/E2-transfected cells as well as hepatocytes infected with cell culture-derived HCV (HCVcc). Results In this proof-of-concept study, retrovirus-transduced human T cells expressing anti-HCV/E2 CARs were endowed with specific antigen recognition accompanied by degranulation and secretion of proinflammatory and antiviral cytokines, such as interferon γ, interleukin 2 and tumour necrosis factor α. Moreover, CAR-grafted T cells were capable of lysing target cells of both hepatic and non-hepatic origin expressing on their surface the HCV/E2 glycoproteins of the most clinically relevant genotypes, including 1a, 1b, 2a, 3a, 4 and 5. Finally, and more importantly, they were capable of lysing HCVcc-infected hepatocytes. Conclusions Clearance of HCV-infected cells is a major therapeutic goal in chronic HCV infection, and adoptive transfer of anti-HCV/E2 CARs-grafted T cells represents a promising new therapeutic tool. PMID:25661083

  13. [Improvement of sensitivity in the second generation HCV core antigen assay by a novel concentration method using polyethylene glycol (PEG)].

    Science.gov (United States)

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

    2007-11-01

    A HCV core antigen (Ag) detection assay system, Lumipulse Ortho HCV Ag has been developed and is commercially available in Japan with a lower detection level limit of 50 fmol/l, which is equivalent to 20 KIU/ml in PCR quantitative assay. HCV core Ag assay has an advantage of broader dynamic range compared with PCR assay, however the sensitivity is lower than PCR. We developed a novel HCV core Ag concentration method using polyethylene glycol (PEG), which can improve the sensitivity five times better than the original assay. The reproducibility was examined by consecutive five-time measurement of HCV patients serum, in which the results of HCV core Ag original and concentrated method were 56.8 +/- 8.1 fmol/l (mean +/- SD), CV 14.2% and 322.9 +/- 45.5 fmol/l CV 14.0%, respectively. The assay results of HCV negative samples in original HCV core Ag were all 0.1 fmol/l and the results were same even in the concentration method. The results of concentration method were 5.7 times higher than original assay, which was almost equal to theoretical rate as expected. The assay results of serially diluted samples were also as same as expected data in both original and concentration assay. We confirmed that the sensitivity of HCV core Ag concentration method had almost as same sensitivity as PCR high range assay in the competitive assay study using the serially monitored samples of five HCV patients during interferon therapy. A novel concentration method using PEG in HCV core Ag assay system seems to be useful for assessing and monitoring interferon treatment for HCV. PMID:18154032

  14. 75 FR 22814 - Guidance for Industry: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1...

    Science.gov (United States)

    2010-04-30

    ... (70 FR 43439), FDA announced the availability of the draft guidance of the same title. FDA received...: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV... Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV): Testing, Product Disposition, and Donor...

  15. 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. PMID:25879258

  16. Persistence of HCV in Acutely-Infected Patients Depletes C24-Ceramide and Upregulates Sphingosine and Sphinganine Serum Levels.

    Science.gov (United States)

    Grammatikos, Georgios; Dietz, Julia; Ferreiros, Nerea; Koch, Alexander; Dultz, Georg; Bon, Dimitra; Karakasiliotis, Ioannis; Lutz, Thomas; Knecht, Gaby; Gute, Peter; Herrmann, Eva; Zeuzem, Stefan; Mavromara, Penelope; Sarrazin, Christoph; Pfeilschifter, Josef

    2016-01-01

    Hepatitis C virus (HCV) substantially affects lipid metabolism, and remodeling of sphingolipids appears to be essential for HCV persistence in vitro. The aim of the current study is the evaluation of serum sphingolipid variations during acute HCV infection. We enrolled prospectively 60 consecutive patients with acute HCV infection, most of them already infected with human immunodeficiency virus (HIV), and serum was collected at the time of diagnosis and longitudinally over a six-month period until initiation of antiviral therapy or confirmed spontaneous clearance. Quantification of serum sphingolipids was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Spontaneous clearance was observed in 11 out of 60 patients (18.3%), a sustained viral response (SVR) in 43 out of 45 patients (95.5%) receiving an antiviral treatment after follow-up, whereas persistence of HCV occurred in six out of 60 patients (10%). C24-ceramide (C24-Cer)-levels increased at follow-up in patients with spontaneous HCV eradication (p < 0.01), as compared to baseline. Sphingosine and sphinganine values were significantly upregulated in patients unable to clear HCV over time compared to patients with spontaneous clearance of HCV infection on follow-up (p = 0.013 and 0.006, respectively). In summary, the persistence of HCV after acute infection induces a downregulation of C24Cer and a simultaneous elevation of serum sphingosine and sphinganine concentrations. PMID:27304952

  17. Loss of immune escape mutations during persistent HCV infection in pregnancy enhances replication of vertically transmitted viruses

    OpenAIRE

    Honegger, Jonathan R; Kim, Seungtaek; Price, Aryn A.; Kohout, Jennifer A.; McKnight, Kevin L.; Prasad, Mona R.; Lemon, Stanley M.; Grakoui, Arash; Walker, Christopher M

    2013-01-01

    Globally, about 1% of pregnant women are persistently infected with the hepatitis C virus (HCV) 1 . Vertical transmission occurs in 3–5% of cases 2 and accounts for most new childhood HCV infections 1,3 . HCV-specific CD8+ cytotoxic T-lymphocytes (CTLs) play a vital role in the clearance of acute infections 4–6 , but in the 60–80% of infections that persist these cells become functionally exhausted or select mutant viruses that escape T-cell recognition 7–9 . Increased HCV replication during ...

  18. HCV INFECTION THROUGH PERFORATING AND CUTTING MATERIAL AMONG CANDIDATES FOR BLOOD DONATION IN BELÉM, BRAZILIAN AMAZON

    Directory of Open Access Journals (Sweden)

    Rubenilson Caldas Valois

    2014-12-01

    Full Text Available This study evaluated epidemiological factors for HCV infection associated with sharing perforating and cutting instruments among candidates for blood donation (CBD in the city of Belém, Pará, Brazilian Amazon. Two definitions of HCV infection cases were used: anti-HCV positivity shown by EIA, and HCV-RNA detection by PCR. Infected and uninfected CBD completed a questionnaire about possible risk factors associated with sharing perforating and cutting instruments. The information was evaluated using simple and multiple logistic regressions. Between May and November 2010, 146 (1.1% persons with anti-HCV antibodies and 106 (0.8% with HCV-RNA were detected among 13,772 CBD in Belém. Risk factors associated with HCV infection based on the EIA (model 1 and PCR (model 2 results were: use of needles and syringes sterilized at home; shared use of razors at home, sharing of disposable razors in barbershops, beauty salons etc.; and sharing manicure and pedicure material. The models of HCV infection associated with sharing perforating and cutting instruments should be taken into account by local and regional health authorities and by those of other countries with similar cultural practices, in order to provide useful information to guide political and public strategies to control HCV transmission.

  19. Are the Real HCV Infection Features in Iranian Patients the Same As What Is Expected?

    Directory of Open Access Journals (Sweden)

    Seyed-Moayed Alavian

    2005-03-01

    Full Text Available Hepatitis Monthly issue 7 contained four clinical trials of pegylated interferon (Peg- IFN plus ribavirin for Iranian patients with chronic hepatitis C infection conducted in four various centers(1-4. Apart from one trial(2, which enrolled only patients with inherited bleeding disorders, three others enrolled heterogeneous HCV infected populations. However, reported sustained virologic response (SVR rate was varied from 50% to 78% in these studies. This wide SVR range might make difficulties for the readers to gain clear data regarding efficacy of this therapeutic regimen on Iranian patients.Almost analogous inclusion and exclusion criteria as well as the details of these four studies allow us to intervene and join the cases and reanalyze the datafrom a single pool. However, the slight differences among these studies will obviously diminish the accuracy and make us discuss the results conservatively. For instance, in the study by Merat et al. none of the patients underwent liver biopsy(2 or Zali et al. excluded cirrhotic patients from the study(4. Moreover, the sensitivities of RT-PCR tests applied to define response to treatment were varied from 100 copies/ml to 600 copies/ml in various studies. In spite of these inevitable biases, our intervention is able to provide useful information.To analyze the data, we applied intention to treat analysis (ITT. ITT analysis is generally interpreted as including all patients who received at least one dose of medication(s, regardless of whether they actually satisfied the entry criteria, the treatment actually received, and subsequent withdrawal or deviation from the protocol(5. Therefore, all patients who do not complete the study are considered to have failure to treatment. It is a strategy to avoid the problems created by omitting dropouts and noncompliant patients, which can introduce bias in the trial, and overestimate clinical effectiveness. Although there is a debate about the validity of excluding

  20. Hepatitis C virus (HCV) in cryoglobulinaemic leukocytoclastic vasculitis (LCV): could the presence of HCV in skin lesions be related to T CD8+ lymphocytes, HLA-DR and ICAM-1 expression?

    Science.gov (United States)

    Bernacchi, E; Civita, L L; Caproni, M; Zignego, A L; Bianchi, B; Monti, M; Fabbri, P; Pasero, G; Ferri, C

    1999-12-01

    An association between mixed cryoglobulinaemia (MC) and hepatotropic viruses, chiefly hepatitis C virus (HCV), has been widely reported. The presence of HCV genomic sequences or HCV-related viral proteins in the serum, purified cryoglobulins, peripheral blood mononuclear cells and into several tissues has suggested an important triggering role for HCV in MC patients. However, only few reports investigated the presence of HCV in cutaneous vasculitis and its potential pathogenetic role. Biopsies of cutaneous purpuric lesions from 5 MC female patients (aged from 40 to 80 years) were carried out for virological and histopathological evaluation. A leukocytoclastic vasculitis pattern was found in 4/5 subjects, while the presence of HCV RNA was detected in 3/5. In only 3 cases biopsy specimens were sufficient for immunohistochemical and direct immunofluorescence (DIF) studies. Immunohistochemical evaluation was performed by means of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP) immune-complexes. In the same skin specimen APAAP and DIF findings were compared with the presence/absence of HCV genomic sequences (PCR technique). In 1 MC patient, the detection of HCV-RNA was associated to a prevalent CD8+ T suppressor pattern with a perivascular and subjunctional distribution as well as an intense expression of second class (HLA-DR) and intercellular adhesion (ICAM-1) molecules on basal keratinocytes, endothelial cells and perivascular infiltrate. These findings suggest a marked inflammatory activation that spreads from endothelial cells to keratinocytes and Langerhans cells. In the 2 HCV-RNA negative specimens the scanty immunopathological staining could indicate a residual activity due to the previous inflammatory event triggered by cryoglobulins. The deposition of circulating HCV-containing immune complexes (CIC) in the skin could be the initial pathogenic event for cryoglobulinemic vasculitis; subsequently CIC could spread from the vascular bed to

  1. Discovery of Metal Ions Chelator Quercetin Derivatives with Potent Anti-HCV Activities

    Directory of Open Access Journals (Sweden)

    Dongwei Zhong

    2015-04-01

    Full Text Available Analogues or isosteres of α,γ-diketoacid (DKA 1a show potent inhibition of hepatitis C virus (HCV NS5B polymerase through chelation of the two magnesium ions at the active site. The anti-HCV activity of the flavonoid quercetin (2 could partly be attributed to it being a structural mimic of DKAs. In order to delineate the structural features required for the inhibitory effect and improve the anti-HCV potency, two novel types of quercetin analogues, 7-O-arylmethylquercetins and quercetin-3-O-benzoic acid esters, were designed, synthesized and evaluated for their anti-HCV properties in cell-based assays. Among the 38 newly synthesized compounds, 7-O-substituted derivative 3i and 3-O-substituted derivative 4f were found to be the most active in the corresponding series (EC50 = 3.8 μM and 9.0 μΜ, respectively. Docking studies suggested that the quercetin analogues are capable of establishing key coordination with the two magnesium ions as well as interactions with residues at the active site of HCV NS5B.

  2. Hepatocyte Turnover in Chronic HCV-Induced Liver Injury and Cirrhosis

    Directory of Open Access Journals (Sweden)

    Nikolaos P. Karidis

    2015-01-01

    Full Text Available Chronic hepatitis C virus (HCV infection may eventually lead to progressive liver fibrosis and cirrhosis through a complex, multistep process involving hepatocyte death and regeneration. Despite common pathogenetic pathways present in all forms of liver cirrhosis irrespective of etiology, hepatocyte turnover and related molecular events in HCV-induced cirrhosis are increasingly being distinguished from even “similar” causes, such as hepatitis B virus- (HBV- related cirrhosis. New insights in HCV-induced hepatocellular injury, differential gene expression, and regenerative pathways have recently revealed a different pattern of progression to irreversible parenchymal liver damage. A shift to the significant role of the host immune response rather than the direct effect of HCV on hepatocytes and the imbalance between antiapoptotic and proapoptotic signals have been investigated in several studies but need to be further elucidated. The present review aims to comprehensively summarize the current evidence on HCV-induced hepatocellular turnover with a view to outline the significant trends of ongoing research.

  3. Detection of Visceral adiposity by Ultrasonography and its relation to insulin resistance in HCV patients

    Directory of Open Access Journals (Sweden)

    Mostafa K.Mohamed1,Gamal Esmat2 , Mohamed Said2 , Mohamed Abdel-

    2010-12-01

    Full Text Available Background: Hepatitis C is a major cause of liver-related morbidity and mortality and represents a major public health problem in Egypt and worldwide. Ultrasonography is a simple non-invasive method for detection of visceral fat, which is directly, correlated with insulin resistance (IR as well as development of type 2 diabetes mellitus. Aim: To assess the validity of detection of visceral adipose tissue area with Ultrasonography and its correlation with IR in HCV patients Materials & Method: The study participants were subcategorized into two groups, Group (I: included 867 healthy subjects with negative (HCV RNA as a control group. Group (II: included 277 patients with chronic HCV as a study group. The 2 groups were subjected to thorough history taking, full clinical examination, Anthropometric study,ultrasonographic examination and laboratory investigations including liver functions, viral markers, and qualitative PCR for HCV RNA ,lipid profile & glucose profile . Results: This study revealed that ultrasonography is a simple, non-invasive, safe method in detection of visceral adiposity, which is correlated significantly with IR in chronic HCV patients

  4. Experimental models for hepatitis C virus (HCV): new opportunities for combating hepatitis C.

    Science.gov (United States)

    Trujillo-Murillo, Karina del Carmen; Garza-Rodríguez, María del Lourdes; Martínez-Rodríguez, Herminia Guadalupe; Barrera-Saldaña, Hugo Alberto; Bosques-Padilla, Francisco; Ramos-Jiménez, Javier; Rivas-Estilla, Ana María

    2004-01-01

    Infection with hepatitis C virus (HCV) is a global public health issue. More than 200 million people in the world are infected with HCV. Hepatitis C is considered one of the main causes of chronic hepatitis, cirrhosis, hepatocellular carcinoma and liver transplantation. The identification of the viral genome quickly allowed delineation of genomic organization, and the structure and biochemical characterization of the proteins of HCV. However, it has been difficult to study its life cycle, as well as the development of antiviral agents due to the lack of a system of permissible culture. Numerous attempts have been reported to establish an in vitro system for the study of HCV. Recently, a system of efficient culture was established that allows replication of subgenomic molecules of HCV in a cell line of human hepatoma. In this revision, after a brief description of the molecular biology, means of transmission and clinical characteristics of hepatitis C, some of the experimental models are described that have been developed to date, focusing mainly on the subgenomic replicon system and their use in the development of new antiviral treatments. PMID:15257247

  5. Seroprevalence of anti-HCV and hepatitis B surface antigen in HIV infected patients

    Directory of Open Access Journals (Sweden)

    Tankhiwale S

    2003-01-01

    Full Text Available Human immunodeficiency virus (HIV is known to influence the natural history of infections with certain hepatitis viruses and interactions between HIV and hepatitis viruses may potentiate HIV replication. There is high degree of epidemiological similarity between hepatitis B virus and HIV as regard to high-risk group and route of transmission. Transmission of hepatitis C virus (HCV through blood transfusion and intravenous drug abuse is well documented. Present study deals with the study of concurrent infection of HBV and HCV with HIV infection. In the study of 110 HIV seropositive patients, 34(30.4% were positive for HBV and 8(7.27% for HCV. The difference of concomitant infection was highly significant compared to controls. (p value < 0.0001. Heterosexual high risk behaviour was observed in 89(80.91% of 110 HIV positive patients, out of which 23(25.8% and 5(5.62% were HBsAg and anti-HCV positive respectively. History of transmission was unclear in remaining patients. Concomitant infection of HIV and HBV was found to be significantly more in the symptomatic group (40.68% compared to asymptomatic group (19.6%. As HIV infection is known to affect the natural history of both HBV and HCV infection, screening of their concurrent association is necessary.

  6. Kinetics of HCV envelope proteins' interaction with CD81 large extracellular loop

    International Nuclear Information System (INIS)

    We used BIAcore to analyze the kinetics of interactions between CD81 and hepatitis C virus (HCV) envelope proteins. We immobilized different forms of HCV envelope proteins (E1E2, E2, and E2661) on the sensor and monitored their interaction with injected fusion proteins of CD81 large extracellular loop (CD81LEL) and glutathione-S-transferase (CD81LEL-GST) or maltose binding protein (CD81LEL-MBP). The difference between the GST and MBP fusion proteins was their multimeric and monomeric forms, respectively. The association rate constants between CD81LEL-GST or CD81LEL-MBP and the E1E2, E2 or E2661 HCV envelope proteins were similar. However, the dissociation rate constants of CD81LEL-MBP were higher than those of CD81LEL-GST. Interestingly, the dissociation rate constant of CD81LEL-GST from E1E2 was much lower than from E2 or E2661. The interaction between both forms of the CD81LEL fusion proteins and the HCV envelope proteins best-fitted the 'heterogeneous ligand' model. This model implies that two kinds of interactions occur between envelope proteins and CD81LEL: one is strong, the other is weak. It also implies that the heterogeneity is likely due to the HCV envelope proteins, which are known to form non-covalently linked heterodimers and disulfide-linked aggregate

  7. Interferon lambda: opportunities, risks and uncertainties in the fight against HCV

    Directory of Open Access Journals (Sweden)

    Stephen M Laidlaw

    2014-10-01

    Full Text Available Innate immunity is key to the fight against the daily onslaught from viruses that our bodies are subjected to. Essential to this response are the interferons (IFNs that prime our cells to block viral pathogens. Recent evidence suggests that the Type III (λ IFNs are intimately associated with the immune response to hepatitis C virus (HCV infection. Genome-wide association studies have identified polymorphisms within the IFN-λ gene locus that correlate with response to IFNα-based antiviral therapy and with spontaneous clearance of HCV infection. The mechanisms for these correlations are incompletely understood. Restricted expression of the IFN-λ receptor, and the ability of IFN-λ to induce IFN-stimulated genes in HCV-infected cells, suggest potential roles for IFN-λ in HCV therapy even in this era of directly acting antivirals. This review summarises our current understanding of the IFN-λ family and the role of λ IFNs in the natural history of HCV infection.

  8. Assessment and development of time-resolved fluoroimmunoassay for antibody of HCV

    International Nuclear Information System (INIS)

    To establish an IFMA of anti-HCV, the antigen of HCV was covered on the micro-well plate, and then incubated with human anti-HCV in sample and Eu3+ labeled goat anti-human IgG. The luminescent enhancement solution contains mainly 2-naphthoyl-trifluoro-acetate, and the data was treated with the log-logit function and four-parameter logistic function. Results showed that the intra-and inter-assay CV of the IFMA was 3.64% and 4.39%, respectively, and the recovery rate was 105.58%, the sensitivity was 0.03 NCU/mL. The cross reactivity with HBsAg and HbeAg was 0.23% and 0.04%, respectively. The anti-HCV concentrations in serum of 278 health persons were all less than 1 NCU/mL. Results indicated this new method was sensitive, stable and could be used as an effective non-radioassay tool for the basic or clinical study on HCV

  9. Signal to cut-off (S/CO ratio and detection of HCV genotype 1 by real-time PCR one-step method: is there any direct relationship?

    Directory of Open Access Journals (Sweden)

    Guilherme Albertoni

    2010-04-01

    Full Text Available BACKGROUND: Polymerase chain reaction (PCR methods play an essential role in providing data related to diagnosis, monitoring and treatment of hepatitis C virus (HCV infection. EIA results are reported as ''reactive'' or ''non reactive'' and EIA S/CO ratio may also be reported as ''high'' or ''low.'' This study aimed to evaluate the performance of a real-time RT-PCR and assess whether there is relationship between S/CO and PCR results. STUDY DESIGN AND METHODS: Sera from blood donors were analyzed by Enzyme-Linked Immunosorbent Assay (ELISA and RT-PCR assay to detect HCV infection. RESULTS: The RT-PCR assay to genotypes 1a/b showed an acceptable linear response in serial dilutions. The samples were divided into two groups based on their serological results: group A - S/CO ratio 3 (41 samples. Viral loads were confirmed positive in group B samples in 90%, and in group A samples were confirmed positive in only 13% by RT-PCR. CONCLUSION: The methodology used was able to detect the presence of RNA-HCV genotype I in 90% of the samples serologically positive in group B. All negative samples were sent to search for other genotypes of HCV (genotypes 2-6 and were confirmed as negative. These data suggests that these negative samples may have HCV RNA viral load below the detection limit of our test (310 IU/ mL, or a false positive result in serological test, or spontaneous viral clearance occurred.

  10. The Impact of PNPLA3 rs738409 SNP on Liver Fibrosis Progression, Portal Hypertension and Hepatic Steatosis in HIV/HCV Coinfection.

    Directory of Open Access Journals (Sweden)

    Bernhard Scheiner

    Full Text Available Faster fibrosis progression and hepatic steatosis are hallmarks of HIV/HCV coinfection. A single nucleotide polymorphism (SNP of the PNPLA3-gene is associated with development of non-alcoholic steatohepatitis and a worse outcome in alcoholic liver disease. However, the role of PNPLA3 rs738409 SNP on liver fibrosis and steatosis, portal hypertension, and virological response in HIV/HCV coinfection remains unclear.In this cross-sectional study PNPLA3 (rs738409 and IL28B (rs12979860 SNPs were determined in 177 HIV/HCV coinfected patients. Liver fibrosis and steatosis-staged by liver biopsy and transient elastography using the Controlled Attenuation Parameter (CAP-and portal hypertension (hepatic venous pressure gradient, HVPG were compared across PNPLA3 genotypes.75 (42.4% patients tested positive for a PNPLA3 minor/major risk allele (G/C:66; G/G:9 showed comparable fibrosis stages (median F2 vs. F2; p = 0.292 and similar amounts of hepatic steatosis (CAP: 203.5 ± 41.9 vs. 215.5 ± 59.7 dB/m; p = 0.563 as compared to patients without a PNPLA3 risk allele. Advanced liver fibrosis was neither associated with PNPLA3 (p = 0.253 nor IL28B-genotype (p = 0.628, but with HCV-GT3 (p = 0.003, higher BMI (p = 0.008 and higher age (p = 0.007. Fibrosis progression rate (0.27 ± 0.41 vs. 0.20 ± 0.26 units/year; p = 0.984 and HVPG (3.9 ± 2.6 vs. 4.4 ± 3.0 mmHg; p = 0.472 were similar in patients with and without PNPLA3 risk alleles. SVR rates to PEGIFN/RBV therapy were similar across PNPLA3 genotypes.The presence of a PNPLA3 risk allele had no independent impact on liver disease or virological response rates to PEGIFN/RBV therapy in our cohort of HIV/HCV coinfected patients.

  11. gC1qR expression in chimpanzees with resolved and chronic infection: Potential role of HCV core/gC1qR-mediated T cell suppression in the outcome of HCV infection

    International Nuclear Information System (INIS)

    Chimpanzee is a unique animal model for HCV infection, in which about 50% of infections resolve spontaneously. It has been reported that the magnitude of T cell responses to HCV core in recovered chimpanzees is greater than that in chronically infected ones. However, the mechanism(s) by which the chimpanzees with resolved infection overcome core-mediated immunosuppression remains unknown. In this study, we examined the effect of HCV core on T cell responsiveness in chimpanzees with resolved and chronic HCV infection. We found that core protein strongly inhibited T cell activation and proliferation in chimpanzees with chronic infection, while this inhibition was limited in chimpanzees with resolved infection. Notably, the level of gC1qR, as well as the binding of core protein, on the surface of T cells was lower in recovered chimpanzees when compared to chimpanzees with chronic HCV infection. Intriguingly, the observed differences in gC1qR expression levels and susceptibility to core-induced suppression amongst HCV-chronically infected and recovered chimpanzees were observed prior to HCV challenge, suggesting a possible genetic determination of the outcome of infection. These findings suggest that gC1qR expression on the surface of T cells is crucial for HCV core-mediated T cell suppression and viral clearance, and that represents a novel mechanism by which a virus usurps host machinery for persistence

  12. HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.

    Science.gov (United States)

    Filbin, Megan E; Vollmar, Breanna S; Shi, Dan; Gonen, Tamir; Kieft, Jeffrey S

    2013-02-01

    The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders. PMID:23262488

  13. Sustained virologic response following HCV eradication in two brothers with X-linked agammaglobulinaemia.

    LENUS (Irish Health Repository)

    Houlihan, Diarmaid D

    2009-08-21

    X-linked agammaglobulinaemia (XLA) is a humoral immunodeficiency syndrome characterized from childhood by the absence of circulating B lymphocytes, absent or reduced levels of serum immunoglobulin and recurrent bacterial infections. For many affected patients, regular treatment with immunoglobulin is life saving. Hepatitis C viral (HCV) infection acquired through contaminated blood products is widely described in this patient cohort. The natural history of HCV infection in patients with XLA tends to follow a more rapid and aggressive course compared to immunocompetent individuals. Furthermore, standard anti-viral therapy appears to be less efficacious in this patient cohort. Here we report the cases of two brothers with XLA who contracted HCV through contaminated blood products. They were treated with a six month course of Interferon alpha-2b and Ribavirin. We report a sustained virologic response five years after completing treatment.

  14. Kan vericilerde HBsAg, anti-HCV, anti-HIV ve Sifilis seroprevalansı

    OpenAIRE

    Altındiş, Mustafa; Aslan, Savaş; Kalaycı, Raike

    2011-01-01

    Bu çalışmada Afyon Kocatepe Üniversitesi Tıp Fakültesi Kan Merkezi'ne başvuran donörlerde HBsAg, anti-HCV, anti-HIV 1/2 ve RPR seroprevalansının tespiti ve oranların yıllara ve cinsiyete göre dağılımının belirlenmesi amaçlanmıştır. Ocak'2001 ve Aralık'2010 tarihleri arasında Kan Merkezi'ne başvuran 37343 kan donörünün HBsAg, anti-HCV, anti-HIV ½ tarama testleri mikropartikül ELISA (Vitros, Ortho-Clinical Diagnostics) yöntemi ile Ortho-Clinical Diagnostics (HBsAg, HCV 3.jenerasyon, HIV 1/2) ki...

  15. Short interferon and ribavirin treatment for HCV genotype 2 or 3 infection

    DEFF Research Database (Denmark)

    Waldenström, Jesper; Färkkilä, Martti; Rembeck, Karolina;

    2016-01-01

    OBJECTIVE: Interferon-free therapy for hepatitis C virus (HCV) infection is costly, and therefore patients with advanced fibrosis are prioritized. Although coupled with considerable side effects, a large proportion of genotype 2/3 infected patients achieve a sustained virological response (SVR......) following interferon-based therapy. The present study evaluates experimental clinical trial and verifying real-life data with the aim of identifying patients with a high likelihood of favorable outcome following short interferon-based treatment. MATERIAL AND METHODS: The impact of established response...... with interferon and ribavirin, 87% of HCV genotype 2 and 79% of genotype 3 infected patients achieved SVR, and among 117 Swedish real-life patients treated for 12-16 weeks, 97% of HCV genotype 2 and 94% of genotype 3 infected achieved SVR. CONCLUSIONS: Short interferon-based therapy offers a high likelihood...

  16. Inhibitory effects of sudanese medicinal plant extracts on hepatitis C virus (HCV) protease.

    Science.gov (United States)

    Hussein, G; Miyashiro, H; Nakamura, N; Hattori, M; Kakiuchi, N; Shimotohno, K

    2000-11-01

    One hundred fifty-two methanol and water extracts of different parts of 71 plants commonly used in Sudanese traditional medicine were screened for their inhibitory effects on hepatitis C virus (HCV) protease (PR) using in vitro assay methods. Thirty-four extracts showed significant inhibitory activity (>/=60% inhibition at 100 microg/mL). Of these, eight extracts, methanol extracts of Acacia nilotica, Boswellia carterii, Embelia schimperi, Quercus infectoria, Trachyspermum ammi and water extracts of Piper cubeba, Q. infectoria and Syzygium aromaticum, were the most active (>/=90% inhibition at 100 microg/mL). From the E. schimperi extract, two benzoquinones, embelin (I) and 5-O-methylembelin (II), were isolated and found as potent HCV-PR inhibitors with IC(50) values of 21 and 46 microM, respectively. Inhibitory activities of derivatives of I against HCV-PR as well as their effects on other serine proteases were also investigated. PMID:11054840

  17. Comparison of Structural Architecture of HCV NS3 Genotype 1 versus Pakistani Genotype 3a

    OpenAIRE

    Kaneez Fatima; Esam Azhar; Shilu Mathew; Ghazi Damanhouri; Ishtiaq Qadri

    2014-01-01

    This study described the structural characterization of Pakistani HCV NS3 GT3a in parallel with genotypes 1a and 1b NS3. We investigated the role of amino acids and their interaction patterns in different HCV genotypes by crystallographic modeling. Different softwares were used to study the interaction pattern, for example, CLCBIO sequence viewer, MODELLER, NMRCLUST, ERRAT score, and MODELLER. Sixty models were produced and clustered into groups and the best model of PK-NCVI/Pk3a NS3 was sele...

  18. Differential predictors of ART adherence among HIV-monoinfected versus HIV/HCV-coinfected individuals.

    Science.gov (United States)

    Shuper, Paul A; Joharchi, Narges; Irving, Hyacinth; Fletcher, David; Kovacs, Colin; Loutfy, Mona; Walmsley, Sharon L; Wong, David K H; Rehm, Jürgen

    2016-08-01

    Although adherence is an important key to the efficacy of antiretroviral therapy (ART), many people living with HIV (PLWH) fail to maintain optimal levels of ART adherence over time. PLWH with the added burden of Hepatitis C virus (HCV) coinfection possess unique challenges that potentially impact their motivation and ability to adhere to ART. The present investigation sought to (1) compare ART adherence levels among a sample of HIV/HCV-coinfected versus HIV-monoinfected patients, and (2) identify whether ART-related clinical and psychosocial correlates differ by HCV status. PLWH receiving ART (N = 215: 105 HIV/HCV-coinfected, 110 HIV-monoinfected) completed a comprehensive survey assessing ART adherence and its potential correlates. Medical chart extraction identified clinical factors, including liver enzymes. Results demonstrated that ART adherence did not differ by HCV status, with 83.7% of coinfected patients and 82.4% of monoinfected patients reporting optimal (i.e., ≥95%) adherence during a four-day recall period (p = .809). Multivariable logistic regression demonstrated that regardless of HCV status, optimal ART adherence was associated with experiencing fewer adherence-related behavioral skills barriers (AOR = 0.56; 95%CI = 0.43-0.73), lower likelihood of problematic drinking (AOR = 0.15; 95%CI = 0.04-0.67), and lower likelihood of methamphetamine use (AOR = 0.14; 95%CI = 0.03-0.69). However, among HIV/HCV-coinfected patients, optimal adherence was additionally associated with experiencing fewer ART adherence-related motivational barriers (AOR = 0.23; 95%CI = 0.08-0.62) and lower likelihood of depression (AOR = 0.06; 95%CI = 0.00-0.84). Findings suggest that although HIV/HCV-coinfected patients may face additional, distinct barriers to ART adherence, levels of adherence commensurate with those demonstrated by HIV-monoinfected patients might be achievable if these barriers are addressed. PMID:26971360

  19. High Seroprevalence of HBV and HCV Infection in HIV-Infected Adults in Kigali, Rwanda

    OpenAIRE

    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

    Background Data on prevalence and incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in Rwanda are scarce. Methods 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 women initiating antiretroviral therapy (ART) at baseline, and 200 women not yet eligible for ART. Results Baseline prevalence of active HBV infection (HBsAg positive), past or occu...

  20. Increased microRNA-155 expression in the serum and peripheral monocytes in chronic HCV infection

    OpenAIRE

    Bala Shashi; Tilahun Yaphet; Taha Odette; Alao Hawau; Kodys Karen; Catalano Donna; Szabo Gyongyi

    2012-01-01

    Abstract Background Hepatitis C Virus (HCV), a single stranded RNA virus, affects millions of people worldwide and leads to chronic infection characterized by chronic inflammation in the liver and in peripheral immune cells. Chronic liver inflammation leads to progressive liver damage. MicroRNAs (miRNA) regulate inflammation (miR-155, -146a and -125b) as well as hepatocyte function (miR-122). Methods Here we hypothesized that microRNAs are dysregulated in chronic HCV infection. We examined mi...

  1. Liver stiffness measurements in patients with HBV vs HCV chronic hepatitis:A comparative study

    Institute of Scientific and Technical Information of China (English)

    Ioan; Sporea; Roxana; Sirli; Alexandra; Deleanu; Adriana; Tudora; Alina; Popescu; Manuela; Curescu; Simona; Bota

    2010-01-01

    AIM:To assess the values of liver stiffness (LS) in pa-tients with hepatitis B virus (HBV) chronic hepatitis and to compare them with those in patients with hepatitis C virus (HCV) chronic hepatitis. METHODS: The study included 140 patients with HBV chronic hepatitis, and 317 patients with HCV chronic hepatitis, in which LS was measured (FibroScan-Echo-sens) and liver biopsy was performed in the same session (assessed according to the Metavir score). RESULTS:According to the Metavir score of the 140 HBV p...

  2. HCV prototype vaccine based on hepatitis B core virus-like particles

    OpenAIRE

    Marija Mihailova

    2008-01-01

    HCV prototype vaccine based on hepatitis B core virus-like particles Abstract In the current study the C-terminally truncated HBc expression vectors were used for exposure of different hepatitis C virus (HCV) protein (core, E2, and NS3) fragments. All created chimeric constructs directed high level of recombinant protein synthesis in E.coli. However, not all chimeric proteins were able to self-assemble into virus-like particles (VLPs). HBcCterm/HVR1tetramer VLPs turned ou...

  3. Interferon lambda 4 signals via the IFNλ receptor to regulate antiviral activity against HCV and coronaviruses

    DEFF Research Database (Denmark)

    Hamming, Ole Jensen; Terczynska-Dyla, Ewa; Vieyres, Gabrielle;

    2013-01-01

    The IFNL4 gene is a recently discovered type III interferon, which in a significant fraction of the human population harbours a frameshift mutation abolishing the IFNλ4 ORF. The expression of IFNλ4 is correlated with both poor spontaneous clearance of hepatitis C virus (HCV) and poor response...... to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNλ4, which signals through the IFNλR1 and IL-10R2 receptor chains. Recombinant IFNλ4 is antiviral against both HCV and coronaviruses at levels comparable to IFNλ3. However, the secretion...

  4. 77 FR 14546 - Announcement of Funding Awards for the Housing Choice Voucher Family Self-Sufficiency (HCV-FSS...

    Science.gov (United States)

    2012-03-12

    ... URBAN DEVELOPMENT Announcement of Funding Awards for the Housing Choice Voucher Family Self-Sufficiency... welfare assistance, and make progress toward economic independence and self-sufficiency. The HCV-FSS... will lead to economic self- sufficiency. As a result of their participation in the HCV-FSS...

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

    DEFF Research Database (Denmark)

    Ramirez, 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 t...

  6. Incidence of HCV and sexually transmitted diseases among hiv positive msm in antwerp, belgium, 2001-2011.

    Science.gov (United States)

    Apers, L; Koole, O; Bottieau, E; Vandenbruaene, M; Ophoff, D; Van Esbroeck, M; Crucitti, T; Florence, E

    2013-01-01

    Recurrent Sexually Transmitted Infections (STIs) are an indication of unsafe sexual practices and may be associated with HCV-infection among HIV-positive men who have sex with men. In a retrospective study we analysed the laboratory data of 99 HIV-positive MSM who acquired HCV during the observation period (cases) and 176 HIV-positive MSM who remained HCV negative during the observation period (controls), all followed at the HIV/STI-clinic in Antwerp, Belgium. All laboratory confirmed STI-episodes were recorded since the date of first consultation at our clinic, until the date of HCV-diagnosis of the cases. The HCV incidence varied between 0.24 (2001) and 1.36 (2011) new cases per hundred person-years, with a peak of 2.93 new cases per hundred person-years in 2009. The number of STI-episodes per person-year follow-up was significantly higher for the cases as compared to the controls for syphilis, non-LGV and LGV Chlamydia infections (p HCV conversion, all laboratory confirmed STIs remained more frequent among cases, but only the difference in syphilis incidence was statistically significant (p HCV and should lead to intensified screening for HCV and counselling of the patient. PMID:24635329

  7. Effects of different anti-HIV therapies on progression of hepatitis C in HCV /HIV-coinfected patients

    Institute of Scientific and Technical Information of China (English)

    孙宏清

    2014-01-01

    Objective To investigate the effect of protease inhibitors(PIs)-or non-nucleoside reverse transcriptase inhibitors(NNR-TIs)-based therapy on the progression of hepatitis C in patients with hepatitis C virus(HCV)/human immunodeficiency virus(HIV)coinfection.Methods A total of 273 patients initially diagnosed with HCV/HIV coinfection were

  8. A study on the relationship of anti-HCV antibody and hepatitis C viremia in post-transfusion hepatitis

    International Nuclear Information System (INIS)

    The specimens of blood transfusion recipients who recieved the Anti-HCV antibody positive bloods were analyzed at irregular intervals by enzyme immunoassay to measure the anti-HCV antibody and reverse transcription PCR of hepatitis C virus to evaluate the viremic states. At the same time, the specimens of anti-HCV antibody positive healthy blood donors are analyzed by the reverse transcription PCR method. We analyzed the 9 cases of anti-HCV positive blood donors by reverse transcription PCR and no cases of positive HCV reverse transcription PCR is found. The 5 patients who recieved the anti-HCV positive blood by blood transfusion was followed at irregular interval. Of 5 blood recipients, Hepatitis C virus was detected in 2 patients (40%) and Anti-HCV antibody was detected in 2 patients (40%). We suppose that in contrast to disease group (Non A non B hepatitis), the possibility of viremia in the anti-HCV positive blood donors is significantly low and the character of those antibody may be convalescent antibody after hepatitis C resolution. (Author)

  9. Quantification of Hepatitis C Virus (HCV) in Liver Specimens and Sera from Patients with Human Immunodeficiency Virus Coinfection by Using the Versant HCV RNA 3.0 (Branched DNA-Based) DNA Assay

    Science.gov (United States)

    Tedeschi, Rosamaria; Pivetta, Eliana; Zanussi, Stefania; Bidoli, Ettore; Ros, Mirna; di Gennaro, Giampiero; Nasti, Guglielmo; De Paoli, Paolo

    2003-01-01

    The new generation assay Versant HCV RNA 3.0v (Bayer Diagnostics) was evaluated to quantify hepatitis C virus (HCV) RNA levels in liver biopsy specimens from patients with HCV and human immunodeficiency virus (HIV) coinfection. A total of 25 liver biopsies and sera collected at the time of liver biopsy were used. The efficiency of HCV RNA recovery from spiked samples was between 38.6 and 50.7%, and reproducible measurements of viral load were observed (the intra- and interrun coefficients of variation were 0.5 to 13% and 3.5 to 24.7%, respectively), with good specificity and sensitivity. Linearity was evaluated in the range of 96,154 to 769 IU/μg by using a serially diluted high-titer sample. Coinfected patients had high HCV RNA viral loads in serum and liver (498,471 IU/ml and 231,495 IU/μg, respectively), and both levels were correlated (r = 0.63; P < 0.01). The amount of hepatic HCV RNA was significantly higher among patients with genotype 1 than among patients with genotype 3 (P < 0.01). The virological end-of-treatment response in the serum was associated with a lower pretreatment intrahepatic HCV viral load (P = 0.03). The new version of b-DNA is a sensitive, specific, and reproducible method for quantitating HCV RNA in the liver. Given its positive analytical performance, the assay will be used to evaluate the HCV RNA levels in the serum and liver during follow-up of patients treated with an anti-HCV therapeutic regimen. PMID:12843041

  10. 山东省HIV与HCV共感染者的流行病学分析%Epidemiological analysis of HIV and HCV co-infection in Shandong

    Institute of Scientific and Technical Information of China (English)

    张树霞; 苏生利; 林彬; 孙晓光; 傅继华

    2013-01-01

    Objective To understand the HCV infection status among HIV infected individuals in Shandong Province, and analyze the epidemiological characteristics of HIV/HCV co-infection. Method The confirmatory blood samples from HIV positive cases reported in Shandong Province from 2000 to 2010 were taken for HCV tests, and the survived HIV positive cases aged above 18 years were selected as the study subjects. Epidemiological information was obtained at the first follow up to those who were confirmed as HIV positive and was subject to one-way ANOVA and multivariate logistic regression analysis. Results The HIV/HCV co-infection rate among the subjects accounted for 41. 7% (842/2 021). The single factor analysis showed that there was a significant difference among the subjects with different educational backgrounds, genders, household registers, routes of transmission, date of confirmation and ethnic (P<0. 05). Furthermore, multivariate logistic repression analysis showed that gender, n-ative places and route of transmission were associated with HIV/HCV co-infection. Conclusion The HIV/HCV co-infection rate is distinct among subjects with different genders, native places and the routes of transmission, to which closer attention should be paid.%目的 了解丙型肝炎病毒(HCV)在山东省艾滋病病毒(HIV)感染者中的感染状况,分析HIV、HCV共感染者的流行病学特征.方法 对2000-2010年底,山东省报告的HIV感染者/艾滋病(AIDS)病人确证时的血样进行HCV检测,选取现在存活的、年龄≥18岁的HIV感染者和AIDS病人为研究对象,通过研究对象HIV确证后的首次随访调查表,收集流行病学信息,进行单因素分析和多因素Logistic回归分析.结果 HIV与HCV共感染率为41.7%(842/2 021).单因素分析发现,不同文化程度、不同性别、籍贯和传染途径、不同民族之间差异有统计学意义(P<0.05),在此基础上进行多因素的Logistic回归分析发现,性别、籍贯和感

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

    Directory of Open Access Journals (Sweden)

    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. Differential efficacy of protease inhibitors against HCV genotypes 2a, 3a, 5a, and 6a NS3/4A protease recombinant viruses

    DEFF Research Database (Denmark)

    Gottwein, Judith M; Scheel, Troels K H; Jensen, Tanja B; Ghanem, Lubna; Bukh, Jens

    2011-01-01

    The hepatitis C virus (HCV) genotype influences efficacy of interferon (IFN)-based therapy. HCV protease inhibitors are being licensed for treatment of genotype 1 infection. Because there are limited or no data on efficacy against HCV genotypes 2-7, we aimed at developing recombinant infectious...... cell culture systems expressing genotype-specific nonstructural (NS) protein 3 protease (NS3P)....

  13. PPARs and HCV-Related Hepatocarcinoma: A Mitochondrial Point of View

    Directory of Open Access Journals (Sweden)

    Francesca Agriesti

    2012-01-01

    Full Text Available Hepatitis-C-virus-related infective diseases are worldwide spread pathologies affecting primarily liver. The infection is often asymptomatic, but when chronically persisting can lead to liver scarring and ultimately to cirrhosis, which is generally apparent after decades. In some cases, cirrhosis will progress to develop liver failure, liver cancer, or life-threatening esophageal and gastric varices. HCV-infected cells undergo profound metabolic dysregulation whose mechanisms are yet not well understood. An emerging feature in the pathogenesis of the HCV-related disease is the setting of a pro-oxidative condition caused by dysfunctions of mitochondria which proved to be targets of viral proteins. This causes deregulation of mitochondria-dependent catabolic pathway including fatty acid oxidation. Nuclear receptors and their ligands are fundamental regulators of the liver metabolic homeostasis, which are disrupted following HCV infection. In this contest, specific attention has been focused on the peroxisome proliferator activated receptors given their role in controlling liver lipid metabolism and the availability of specific pharmacological drugs of potential therapeutic utilization. However, the reported role of PPARs in HCV infection provides conflicting results likely due to different species-specific contests. In this paper we summarize the current knowledge on this issue and offer a reconciling model based on mitochondria-related features.

  14. STUDY OF VIRAL MARKERS (HIV, HBV, HCV IN A TERTIARY CARE HOSPITAL

    Directory of Open Access Journals (Sweden)

    Samatha

    2015-10-01

    Full Text Available BACKGROUND: Viral infections are global health problems, affecting millions. Studies show wide variations in the prevalence patterns of the Human Immuno deficiency, Hepatitis B and Hepatitis C Virus infections. Prevalence of these infections may vary not only from country to country but also in different regions of the same country . The present study was designed to find out the sero - prevalence of HBV, HCV, and HIV infections in patients attending a tertiary care hospital. METHODS: A prospective study was conducted for a period of one year from April 2014 to March 2015. A total of 4 276 patients were screened for Hepatitis B surface Antigen ( HBsAg, anti HCV antibodies and anti HIV antibodies. Patients with symptoms or signs of these viral infections and the patients for routine pre - surgical evaluation, referred by the clinicians were included in the study. Age, sex and serological result data was analysed for these patients. The results were analysed by Chi - square statistics. RESULTS: The sero - prevalence of HBsAg was 2.5%, anti HCV antibodies was 0.63%, anti HIV antibodies was 1.73% whereas, co - infection of HBsAg with HIV was seen in only three patients. CONCLUSION: In the present study, the sero - prevalence of Hepatitis B Virus (HBV was higher than HIV and HCV infections. As these viral infections are dangerous and cause morbidity an d mortality, population based awareness & screening programmes are recommended to limit the further spread.

  15. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm

    DEFF Research Database (Denmark)

    Razavi, H; Waked, I; Sarrazin, C;

    2014-01-01

    The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total...

  16. CASE REPORT OF DCR DONE IN A HCV POSITIVE PATIENT ON PACEMAKER.

    Directory of Open Access Journals (Sweden)

    Santhosh Kumar Sajane

    2015-12-01

    Full Text Available Reporting a case of non-cardiac surgical management of a HCV positive patient with implanted cardiac device. Discussing patient monitoring, endonasal surgical management of dacrocystitis and expected complications during intra operative & post-operative period. Preventing these complications by taking proper precautionary steps.

  17. Effect of hcv infection on hepatic fibrosis in patients of thalassaemia major

    International Nuclear Information System (INIS)

    Objective: To investigate the effect of HCV infection on hepatic fibrosis in patients of thalassaemia major with iron overload in order to modify Pesaro criteria for classification into prognostic groups for allogenic haemopoietic stem cell transplant in these patients. Design: Cross-sectional comparative study. Place and Duration of Study: Armed Forces Institute of Pathology, Armed Forces Bone Marrow Transplant Center and Departments of Pediatrics of Military Hospital and Combined Military Hospital, Rawalpindi, from July 2003 to June 2004. Subjects and Methods: Twenty eight HCV- and 18 HCV+ patients of thalassaemia major, who were prospective recipients of allogeneic bone marrow transplant, were included in the study. Serum ferritin was estimated by chemiluminescent immunoassay. Degree of fibrosis in liver biopsy was scored using Knodell's scoring system. Correlation between the two was evaluated statistically through Pearson's correlation coefficient. Results: Mean serum ferritin was lower and degree of hepatic fibrosis was less in hepatitis C negative patients of TM. The correlation between serum ferritin and the degree of hepatic fibrosis was much stronger in hepatitis C negative patients with 'r' value of 0.507 and 'p' value of 0.006, which was statistically significant. Conclusion: A strong correlation between serum ferritin and degree of hepatic fibrosis was observed in patients of thalassaemia major not infected with hepatitis C infection. Serum ferritin levels alone are, therefore, not sufficient to assess degree of fibrosis in HCV positive patients of TM. (author)

  18. Favourable SVR12 rates with boceprevir or telaprevir triple therapy in HIV/HCV coinfected patients

    NARCIS (Netherlands)

    Arends, J. E.; van der Meer, J. T. M.; Posthouwer, D.; Kortmann, W.; Brinkman, K.; van Assen, S.; Smit, C.; van der Valk, M.; van der Ende, M.; Schinkel, J.; Reiss, P.; Richter, C.; Hoepelman, A. I. M.

    2015-01-01

    Background: Recent publications have reported superior efficacy of telaprevir-or boceprevir-based triple therapy over conventional peginterferon-alfa/ribavirin therapy, albeit with varying rates of adverse events and treatment discontinuations in HIV/HCV coinfected patients. Therefore, the aim of th

  19. Favourable SVR12 rates with boceprevir or telaprevir triple therapy in HIV/HCV coinfected patients

    NARCIS (Netherlands)

    Arends, J. E.; van der Meer, J. T M; Posthouwer, D.; Kortmann, W.; Brinkman, K.; van Assen, S.; Smit, C.; van der Valk, M.; van der Ende, M.; Schinkel, J.; Reiss, P.; Richter, C.; Hoepelman, A. I M

    2015-01-01

    Background: Recent publications have reported superior efficacy of telaprevir- or boceprevir-based triple therapy over conventional peginterferon-alfa/ribavirin therapy, albeit with varying rates of adverse events and treatment discontinuations in HIV/ HCV coinfected patients. Therefore, the aim of

  20. Tissue donation and virus safety: more nucleic acid amplification testing is needed.

    Science.gov (United States)

    Pruss, A; Caspari, G; Krüger, D H; Blümel, J; Nübling, C M; Gürtler, L; Gerlich, W H

    2010-10-01

    In tissue and organ transplantation, it is of great importance to avoid the transmission of blood-borne viruses to the recipient. While serologic testing for anti-human immunodeficiency virus (HIV)-1 and -2, anti-hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg), anti-hepatitis B core antigen (HBc), and Treponema pallidum infection is mandatory, there is until now in most countries no explicit demand for nucleic acid amplification testing (NAT) to detect HIV, hepatitis B virus (HBV), and HCV infection. After a review of reports in the literature on viral transmission events, tissue-specific issues, and manufacturing and inactivation procedures, we evaluated the significance of HIV, HCV, and HBV detection using NAT  in  donors of various types of tissues and compared our results with the experiences of blood banking organizations. There is a significant risk of HIV, HCV, and HBV transmission by musculoskeletal tissues because of their high blood content and the high donor-recipient ratio. If no effective virus inactivation procedure for musculoskeletal tissue is applied, donors should be screened using NAT  for  HIV, HCV, and HBV. Serologically screened cardiovascular tissue carries a very low risk of HIV, HCV, or HBV transmission. Nevertheless, because effective virus inactivation is impossible (retention of tissue morphology) and the donor-recipient ratio may be as high as 1:10, we concluded that NAT  should be performed for HIV, HCV, and HBV as an additional safety measure. Although cornea allografts carry the lowest risk of transmitting HIV, HCV, and HBV  owing to corneal physiology, morphology, and the epidemiology of corneal diseases, NAT  for  HCV should still be performed. If the NAT  screening of a donor for HIV, HCV, and HBV is negative, quarantine storage of the donor tissue seems dispensable. In view of numerous synergistic effects with transfusion medicine, it would be advantageous for tissue banks to cooperate with blood

  1. CD4⁺ and CD8⁺ regulatory T cells (Tregs) are elevated and display an active phenotype in patients with chronic HCV mono-infection and HIV/HCV co-infection

    DEFF Research Database (Denmark)

    Hartling, H J; Gaardbo, J C; Ronit, A;

    2012-01-01

    The aim of this study was to examine regulatory T cells (Tregs) in peripheral blood and liver tissue in patients with chronic hepatitis C virus (HCV) mono-infection and in patients with HIV/HCV co-infection. In a cross-sectional study were included 51 patients with chronic HCV infection, 24...... patients with HIV/HCV co-infection and 24 healthy individuals. CD4⁺ and CD8⁺ Tregs were determined using flow cytometry. Fibrosis was examined by transient elastography. Inflammation, fibrosis and Tregs were determined in liver biopsies from 12 patients. Increased frequency of CD4⁺ and CD8⁺ Tregs was found...... in HIV/HCV co-infected patients [median: 6.4% (IQR: 5.7-6.9) and 1.0% (0.7-1.2), respectively] compared to HCV mono-infected patients [5.6% (4.2-6.3), P = 0.01 and 0.5% (0.3-0.7), P < 0.001, respectively]. Furthermore, HCV mono-infected patients had increased frequencies of Tregs compared with...

  2. Low Efficacy of Pegylated Interferon plus Ribavirin plus Nitazoxanide for HCV Genotype 4 and HIV Coinfection

    Science.gov (United States)

    Macías, Juan; López-Cortés, Luis F.; Téllez, Francisco; Recio, Eva; Ojeda-Burgos, Guillermo; Ríos, MªJosé; Rivero-Juárez, Antonio; Delgado, Marcial; Jeremías, Rivas-; Pineda, Juan A.

    2015-01-01

    Background Nitazoxanide (NTZ) plus pegylated interferon and ribavirin (Peg-IFN/RBV) improved the sustained virological response (SVR) achieved with Peg-IFN/RBV in hepatitis C virus genotype 4 (HCV-4)-monoinfected patients. There are no data currently on the efficacy of Peg-IFN/RBV plus NTZ for human immunodeficiency virus (HIV)/HCV-4 coinfection. Therefore, the objectives of this clinical trial were to assess the efficacy and to evaluate the safety of Peg-IFN/RBV plus NTZ in HIV/HCV-4-coinfected patients. Patients and Methods This was an open-label, single arm, multicenter phase II pilot clinical trial (NCT01529073) enrolling HIV-infected individuals with HCV-4 chronic infection, naïve to HCV therapy. Patients were treated with NTZ 500 mg bid for 4 weeks, followed by NTZ 500 mg bid plus Peg-IFN alpha-2b 1.5 μg/kg/week plus weight-adjusted RBV during 48 weeks. Analyses were done by intention-to-treat (ITT, missing = failure). A historical cohort of HIV/HCV-4-infected patients treated with Peg-IFN alpha-2b and RBV at the same area was used as control. Results Two (9.5%) of 21 patients included in the trial compared with 5 (21.7%) of 23 patients included in the historical cohort achieved SVR (SVR risk difference, -12.2%; 95% confidence interval, -33.2% to 8.8%; p = 0.416). Virological failure was due to lack of response in 13 (62%) individuals recruited in the trial. Two (9.5%) patients included in the trial and two (9.5%) individuals from the historical cohort discontinued permanently due to adverse events. Conclusions No increase in SVR was observed among HIV/HCV-4-coinfected patients receiving Peg-IFN/RBV plus NTZ compared with a historical cohort treated with Peg-IFN/RBV. Interruptions due to adverse events of Peg-IFN/RBV plus NTZ were similar to those of dual therapy. Trial Registration ClinicalTrials.gov NCT01529073 PMID:26640956

  3. Renal function is impaired in normotensive chronic HCV patients: role of insulin resistance.

    Science.gov (United States)

    Sciacqua, Angela; Perticone, Maria; Tassone, Eliezer J; Cimellaro, Antonio; Caroleo, Benedetto; Miceli, Sofia; Andreucci, Michele; Licata, Anna; Sesti, Giorgio; Perticone, Francesco

    2016-06-01

    Renal dysfunction is an independent predictor for cardiovascular morbidity and mortality. We investigated whether chronic hepatitis C virus (HCV) infection and the related insulin resistance/hyperinsulinemia influence renal function in comparison with a group of healthy subjects and with another group with metabolic syndrome. We enrolled 130 newly diagnosed HCV outpatients matched for age and gender with 130 patients with metabolic syndrome and 130 healthy subjects. Renal function was evaluated by calculation of glomerular filtration rate (e-GFR, mL/min/1.73 m(2)) using the CKD-EPI equation. The following laboratory parameters were measured: fasting plasma glucose and insulin, total, LDL- and HDL-cholesterol, triglyceride, creatinine, and HOMA to evaluate insulin sensitivity. HCV patients with respect to both healthy subjects and metabolic syndrome patients have a decreased e-GFR: 86.6 ± 16.1 vs 120.2 ± 23.1 mL/min/1.73 m(2) (P analysis, the correlation between e-GFR and HOMA is similar in the metabolic syndrome (r = -0.555, P analysis, HOMA is the major determinant of e-GFR in both groups, accounting for, respectively, 30.8 and 27.8 % of its variation in the metabolic syndrome and HCV. In conclusion, we demonstrate that HCV patients have a significant reduction of e-GFR and that insulin resistance is the major predictor of renal dysfunction. PMID:26597876

  4. 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

  5. Claudin-1 required for HCV virus entry has high potential for phosphorylation and O-glycosylation

    Directory of Open Access Journals (Sweden)

    Fouzia Kiran

    2011-05-01

    Full Text Available Abstract HCV is a leading cause of hepatocellular carcinoma and cirrhosis all over the world. Claudins belong to family of tight junction's proteins that are responsible for establishing barriers for controlling the flow of molecules around cells. For therapeutic strategies, regulation of viral entry into the host cells holds a lot of promise. During HCV infection claudin-1 is highly expressed in liver and believed to be associated with HCV virus entry after HCV binding with or without co-receptor CD81. The claudin-1 assembly with tight junctions is regulated by post translational modifications. During claudins assembly and disassembly with tight junctions, phosphorylation is required at C-terminal tail. In cellular proteins, interplay between phosphorylation and O-β-GlcNAc modification is believed to be functional switch, but it is very difficult to monitor these functional and vibrant changes in vivo. Netphos 2.0 and Disphos 1.3 programs were used for potential phosphorylation; NetPhosK 1.0 and KinasePhos for kinase prediction; and YinOYang 1.2 and OGPET to predict possible O-glycosylation sites. We also identified Yin Yang sites that may have potential for O-β-GlcNAc and phosphorylation interplay at same Ser/Thr residues. We for the first time proposed that alternate phosphorylation and O-β-GlcNAc modification on Ser 192, Ser 205, Ser 206; and Thr 191 may provide an on/off switch to regulate assembly of claudin-1 at tight junctions. In addition these phosphorylation sites may be targeted by novel chemotherapeutic agents to prevent phosphorylation lead by HCV viral entry complex.

  6. Chaperone-Mediated Autophagy Targets IFNAR1 for Lysosomal Degradation in Free Fatty Acid Treated HCV Cell Culture.

    Directory of Open Access Journals (Sweden)

    Ramazan Kurt

    Full Text Available Hepatic steatosis is a risk factor for both liver disease progression and an impaired response to interferon alpha (IFN-α-based combination therapy in chronic hepatitis C virus (HCV infection. Previously, we reported that free fatty acid (FFA-treated HCV cell culture induces hepatocellular steatosis and impairs the expression of interferon alpha receptor-1 (IFNAR1, which is why the antiviral activity of IFN-α against HCV is impaired.To investigate the molecular mechanism by which IFNAR1 expression is impaired in HCV cell culture with or without free fatty acid-treatment.HCV-infected Huh 7.5 cells were cultured with or without a mixture of saturated (palmitate and unsaturated (oleate long-chain free fatty acids (FFA. Intracytoplasmic fat accumulation in HCV-infected culture was visualized by oil red staining. Clearance of HCV in FFA cell culture treated with type I IFN (IFN-α and Type III IFN (IFN-λ was determined by Renilla luciferase activity, and the expression of HCV core was determined by immunostaining. Activation of Jak-Stat signaling in the FFA-treated HCV culture by IFN-α alone and IFN-λ alone was examined by Western blot analysis and confocal microscopy. Lysosomal degradation of IFNAR1 by chaperone-mediated autophagy (CMA in the FFA-treated HCV cell culture model was investigated.FFA treatment induced dose-dependent hepatocellular steatosis and lipid droplet accumulation in HCV-infected Huh-7.5 cells. FFA treatment of infected culture increased HCV replication in a concentration-dependent manner. Intracellular lipid accumulation led to reduced Stat phosphorylation and nuclear translocation, causing an impaired IFN-α antiviral response and HCV clearance. Type III IFN (IFN-λ, which binds to a separate receptor, induces Stat phosphorylation, and nuclear translocation as well as antiviral clearance in FFA-treated HCV cell culture. We show here that the HCV-induced autophagy response is increased in FFA-treated cell culture

  7. Enhancement of canonical Wnt/β-catenin signaling activity by HCV core protein promotes cell growth of hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Jiao Liu

    Full Text Available BACKGROUND: The Hepatitis C virus (HCV core protein has been implicated as a potential oncogene or a cofactor in HCV-related hepatocellular carcinoma (HCC, but the underlying mechanisms are unknown. Overactivation of the Wnt/β-catenin signaling is a major factor in oncogenesis of HCC. However, the pathogenesis of HCV core-associated Wnt/β-catenin activation remains to be further characterized. Therefore, we attempted to determine whether HCV core protein plays an important role in regulating Wnt/β-catenin signaling in HCC cells. METHODOLOGY: Wnt/β-catenin signaling activity was investigated in core-expressing hepatoma cells. Protein and gene expression were examined by Western blot, immunofluorescence staining, RT-qPCR, and reporter assay. PRINCIPAL FINDINGS: HCV core protein significantly enhances Tcf-dependent transcriptional activity induced by Wnt3A in HCC cell lines. Additionally, core protein increases and stabilizes β-catenin levels in hepatoma cell line Huh7 through inactivation of GSK-3β, which contributes to the up-regulation of downstream target genes, such as c-Myc, cyclin D1, WISP2 and CTGF. Also, core protein increases cell proliferation rate and promotes Wnt3A-induced tumor growth in the xenograft tumor model of human HCC. CONCLUSIONS/SIGNIFICANCE: HCV core protein enhances Wnt/β-catenin signaling activity, hence playing an important role in HCV-associated carcinogenesis.

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

    Directory of Open Access Journals (Sweden)

    Samira Mohammadi Yeganeh

    2012-06-01

    Full Text Available Background and Objectives: 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.Materials and Methods: 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.Results: The analysis of scalar concentrations of the samples indicated that the limit of quantification of the assay was < 1000 copies/ml for HIV-1 and < 500copies/ml for HCV with 95% confidence interval. Multiplex NASBA assay showed a 98% sensitivity and 100% specificity. The analytical specificity study with BLAST software demonstrated that the primers do not attach to any other sequences except for that of HIV-1 or HCV. The primers and molecular beacon probes detected all HCV genotypes and all major variants of HIV-1.Conclusion: This method may represent a relatively inexpensive isothermal method for detection of HIV-1/HCV co-infection in monitoring of patients.

  9. MBL2 Genetic Variants in HCV Infection Susceptibility, Spontaneous Viral Clearance and Pegylated Interferon Plus Ribavirin Treatment Response.

    Science.gov (United States)

    Zupin, L; Polesello, V; Alberi, G; Moratelli, G; Crocè, S L; Masutti, F; Pozzato, G; Crovella, S; Segat, L

    2016-07-01

    Hepatitis C is disease that damages the liver, and it is caused by the hepatitis C virus (HCV). The pathology became chronic in about 80% of the cases due to virus persistence in the host organism. The standard of care consists of pegylated interferon plus ribavirin; however, the treatment response is very variable and different host/viral factors may concur in the disease outcome. The mannose-binding protein C (MBL) is a component of the innate immune system, able to recognize HCV and consecutively activating the immune response. MBL is encoded by MBL2 gene, and polymorphisms, two in the promoter region (H/L and X/Y) and three in exon 1 (at codon 52, 54 and 57), have been described as functionally influencing protein expression. In this work, 203 Italian HCV patients and 61 healthy controls were enrolled and genotyped for the five MBL2 polymorphisms mentioned above to investigate their role in HCV infection susceptibility, spontaneous viral clearance and treatment response. MBL2 polymorphisms were not associated with HCV infection susceptibility and with spontaneous viral clearance, while MBL2 O allele, O/O genotype, HYO haplotype and DP combined genotype (all correlated with low or deficient MBL expression) were associated with sustained virological response. Moreover, a meta-analysis to assess the role of MBL2 polymorphisms in HCV infection susceptibility was also performed: YA haplotype could be associated with protection towards HCV infection. PMID:27136459

  10. 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.

  11. Tumor Necrosis Factor Receptor 1 Expression Is Upregulated in Dendritic Cells in Patients with Chronic HCV Who Respond to Therapy

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    Raul Cubillas

    2010-01-01

    Full Text Available The present studies assessed the level of tumor necrosis factor receptor (TNFR expression in peripheral blood mononuclear cells (PBMCs subsets from patients with chronic HCV undergoing interferon /ribavirin-based therapy (Ifn/R. Methods. TNFR family member mRNA expression was determined using quantitative real-time PCR assays (RTPCRs in PBMC from 39 HCV+ patients and 21 control HCV− patients. Further subset analysis of HCV + patients (untreated (U, sustained virological responders (SVR, and nonresponders (NR/relapsers (Rel PBMC was performed via staining with anti-CD123, anti-CD33, anti-TNFR1 or via RTPCR for TNFR1 mRNA. Results. A similar level of TNFR1 mRNA in PBMC from untreated HCV+ genotype 1 patients and controls was noted. TNFR1 and TNFR2 mRNA levels in PBMC from HCV+ patients with SVR were statistically different than levels in HCV(− patients. A significant difference was noted between the peak values of TNFR1 of the CD123+ PBMC isolated from SVR and the NR/Rel. Conclusion. Upregulation of TNFR1 expression, occurring in a specific subset of CD123+ dendritic cells, appeared in HCV+ patients with SVR.

  12. Genomic analysis reveals a potential role for cell cycle perturbation in HCV-mediated apoptosis of cultured hepatocytes.

    Directory of Open Access Journals (Sweden)

    Kathie-Anne Walters

    2009-01-01

    Full Text Available The mechanisms of liver injury associated with chronic HCV infection, as well as the individual roles of both viral and host factors, are not clearly defined. However, it is becoming increasingly clear that direct cytopathic effects, in addition to immune-mediated processes, play an important role in liver injury. Gene expression profiling during multiple time-points of acute HCV infection of cultured Huh-7.5 cells was performed to gain insight into the cellular mechanism of HCV-associated cytopathic effect. Maximal induction of cell-death-related genes and appearance of activated caspase-3 in HCV-infected cells coincided with peak viral replication, suggesting a link between viral load and apoptosis. Gene ontology analysis revealed that many of the cell-death genes function to induce apoptosis in response to cell cycle arrest. Labeling of dividing cells in culture followed by flow cytometry also demonstrated the presence of significantly fewer cells in S-phase in HCV-infected relative to mock cultures, suggesting HCV infection is associated with delayed cell cycle progression. Regulation of numerous genes involved in anti-oxidative stress response and TGF-beta1 signaling suggest these as possible causes of delayed cell cycle progression. Significantly, a subset of cell-death genes regulated during in vitro HCV infection was similarly regulated specifically in liver tissue from a cohort of HCV-infected liver transplant patients with rapidly progressive fibrosis. Collectively, these data suggest that HCV mediates direct cytopathic effects through deregulation of the cell cycle and that this process may contribute to liver disease progression. This in vitro system could be utilized to further define the cellular mechanism of this perturbation.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

    Zhuang Xun; Liang Yanxian; Chow Eric PF; Wang Yafei; Wilson David P; Zhang Lei

    2012-01-01

    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 clie...

  15. Multiparametric Analyses of Human PBMCs Loaded Ex Vivo with a Candidate Idiotype Vaccine for HCV-Related Lymphoproliferative Disorders

    OpenAIRE

    Annacarmen Petrizzo; Maria Lina Tornesello; Maria Napolitano; Giovanna D'Alessio; Angelo Salomone Megna; Riccardo Dolcetti; Valli De Re; Ena Wang; Marincola, Franco M.; Buonaguro, Franco M; Luigi Buonaguro

    2012-01-01

    Hepatitis C virus (HCV) has been identified as one of the major risk factors for type II mixed cryoglobulinemia (MC), during the clinical evolution of chronic hepatitis, which may lead to development of B cell non-Hodgkin's lymphoma (NHL). We have previously shown that the candidate idiotype vaccine, based on the IGKV3-20 light chain protein, is able to induce activation and maturation of circulating antigen presenting cells (APCs) in both HCV-positive and HCV-negative healthy control subject...

  16. Effect of oral care gel on the quality of life for oral lichen planus in patients with chronic HCV infection

    OpenAIRE

    Sata Michio; Nagao Yumiko

    2011-01-01

    Abstract Background Oral lichen planus (OLP) decreases the quality of life because it can cause spontaneous pain during eating and tooth-brushing and an uncomfortable feeling in the mouth. In addition, OLP may be associated with HCV-related liver disease. We investigated the visual analogue scale (VAS) and effects of oral care gel, REFRECARE-H®, on patients with OLP associated with HCV infection. Results Nine OLP patients (mean age 67.9 ± 7.6 years) with HCV-related liver diseases were recrui...

  17. Recurrence of occult hepatitis B virus infection in a recipient of a liver transplant for HCV-related cirrhosis: full length genome, mutations analysis and literature review

    Directory of Open Access Journals (Sweden)

    Tahar Bajjou

    2014-08-01

    Full Text Available The outcome of liver transplant recipients in HCV chronic carriers with Anti-HBc only concerning occult HBV infection is unknown. We report here the case of a patient who underwent liver transplantation (LT for cirrhosis post chronic hepatitis C who received an allograft from a donor with no marker of hepatitis B infection. After LT, HBV DNA was detected in the serum in the absence of HBsAg while HCV RNA remained negative. To determine the origin of this occult HBV infection, we retrospectively examined stored serum and liver tissue, pre and post-transplantation, for HBV DNA by PCR. A stored liver biopsy of the donor before transplantation was also tested. HBV DNA was detected in the pre-transplant liver but not in the donor liver. HBV viral load quantified by real time PCR after LT ranged from about 102 to 5x103 HBV DNA copies/mg of liver, while in sera, concentrations ranged from 102 to 3x103 HBV DNA copies/ml. All PCR products in the S gene from liver and sera were sequenced. Analysis of sequences showed the presence of an HBV strain genotype D. The nucleotide homology between the patient's HBV strains before and after LT was 96 % across the analyzed regions. Full length HBV genomes were amplified from the sera using Rolling Circle Amplification and then sequenced. Analysis of sequences confirmed the genotype D, but did not show obvious mutations that could contribute to HBsAg seronegativity and low HBV viral replication. Factors leading to occult HBV infection are still unclear, but it is well establish that occult HBV infection is frequent in HCV patients. This underlines the role of extra hepatic sites for HBV replication, potentially lymphocytes acting as and ldquo;reservoirs and rdquo;. [Int J Res Med Sci 2014; 2(4.000: 1294-1301

  18. Insulin resistance and steatosis in HBV-HCV co-infected patients: Role of PNPLA3 polymorphisms and impact on liver fibrosis progression

    Institute of Scientific and Technical Information of China (English)

    Rosa; Zampino; Adriana; Boemio; Aldo; Marrone; Luciano; Restivo; Maria; Chiara; Fascione; Riccardo; Nevola; Luigi; Elio; Adinolfi; Nicola; Coppola; Carmine; Minichini; Mario; Starace; Evangelista; Sagnelli; Grazia; Cirillo; Emanuele; Miraglia; del; Giudice; Maria; Stanzione; Emanuele; Durante-Mangoni; Giovanna; Salzillo

    2014-01-01

    AIM:To evaluate steatosis,insulin resistance(IR)and patatin-like phospholipase domain-containing 3(PNPLA3) and their relation to disease progression in hepatitis B and C viruses(HCV-HBV) coinfected patients.METHODS:Three hundred and thirty patients with biopsy proven chronic hepatitis were enrolled:66 had HBV-HCV,66 HBV and 198 HCV infection.Prevalence of steatosis,IR and PNPLA3 polymorphisms and their relation to anthropometric,biochemical,virological and histological parameters were evaluated.RESULTS:Prevalence of steatosis in group HBV-HCV was similar to that in HCV(47.0% vs 49.5%,respec-tively);group HBV showed the lowest steatosis(33.3%).Group HBV-HCV had a lesser degree of steatosis than HCV(P = 0.016),lower HCV RNA levels(P = 0.025) and lower prevalence and degree of IR(P = 0.01).PNPLA3 polymorphisms were associated with steatosis.Group HBV-HCV showed higher levels of liver fibrosis than group HCV(P = 0.001),but similar to that ob-served in HBV group.In HBV-HCV group,liver fibrosis was not associated with steatosis,IR or PNPLA3.HBV infection was the independent predictor of advanced liver fibrosis.CONCLUSION:HBV-HCV co-infected patients have lower degree of hepatic steatosis,IR and HCV RNA than HCV mono-infected;co-infected patients showed a more rapid liver fibrosis progression that seems to be due to the double infection and/or HBV dominance.

  19. Seroprevalencia de VHB, VHC y VIH en donadores de sangre en Irapuato, México Seroprevalence of HBV, HCV and HIV in blood donors in Irapuato, Mexico

    Directory of Open Access Journals (Sweden)

    Miguel Angel Carreto-Vélez

    2003-01-01

    General Hospital No. 2 Family Medicine Unit, of the Mexican Social Security Institute in Irapuato, Mexico. MATERIAL AND METHODS: A cross-sectional descriptive study. Data was recorded on blood bank forms, and risk factors and illnesses were studied in the 7,056 blood donors at the General Hospital No. 2 Family Medicine Unit, of the Mexican Social Security Institute in Irapuato, Guanajuato, Mexico, over a period of two years (from July 1998 to June 2000. A sample of 4,010 donors was obtained, each of whom underwent serological tests for HBV, HCV and HIV, serotypes 1 and 2, using an enzymatic immunoassay of third generation in serum or human plasma; seroprevalence rate of seropositive donors was calculated and stratified by age and sex. RESULTS: The combined seroprevalence for HBV, HCV and HIV was 2.5% (101; HCV was 1.14% (46, HBV, 1.12% (45, and HIV, 0.24% (10. In males, HBV was 1.04% (33, HCV 1.07% (34, and HIV, 0.28% (9. In females, HBV was 1.42% (12, HCV was 1.42% (12, and HIV was 0.11% (1. Seropositive males had a 2.4 higher rate as compared to females. CONCLUSIONS: The seroprevalence of viral markers was greater than that reported in previous studies carried out in Mexico, which suggests that sexual transmission was the principal mechanism of infection; this reflects poor health education and the need to carefully select potential donors.

  20. A new decision model for economic evaluation of novel therapies for HCV

    Directory of Open Access Journals (Sweden)

    Matteo Ruggeri

    2014-09-01

    Full Text Available In 2014, the European Medicines Agency (EMA has given the license to two new direct-acting antiviral: sofosbuvir and simeprevir. The evidence provided by the studies, reported a high rate of SVR even in patients with decompensated cirrhosis. This and other innovative elements are potentially adept at changing the entire natural course of HCV. However, the dramatic prevalence rates of HCV observed in Italy, and the high prices that are expected to be required by the pharmaceutical industry, raises some critical issues about how to regulate access to such drugs. The objective of this article is to present a new decision model for the evaluation of novel therapies for HCV. This model is intended to provide a tool for the decision-maker that seeks to address the main issues related to the introduction of HCV new treatments. The model that we have structured follows the classic Bayesian approach, using data from reference literature for staging the action of treatments depending on the level of fibrosis (F0, F1, F2, F3, F4. The model is designed to consider patients with all genotypes and allows to make comparisons between innovative and traditional therapies (dual, triple, IFN free, PI combinations, etc., for both experienced and naïve patients. In addition, the model is used to simulate mixed cohorts of patients, representing a population with HCV with different levels of fibrosis and different genotypes. To show the potential of the model, we created some simple scenarios assuming different levels of SVR and pricing. The results of our model show that, even assuming an SVR rate of 100%, the administration of new treatments for HCV subjects F1 / 2 has an incremental cost-effectiveness ratio not sustainable. In contrast, for the subjects F3 and F4, low incremental SVR rates and an incremental cost of the innovative therapy of € 40,000 would be cost effective. The added value of this model is its versatility and applicability to diverse assessment

  1. Patient Characteristics Associated with HCV Treatment Adherence, Treatment Completion, and Sustained Virologic Response in HIV Coinfected Patients

    Directory of Open Access Journals (Sweden)

    Glenn Wagner

    2011-01-01

    Full Text Available Background. Hepatitis C (HCV treatment efficacy among HIV patients is limited by poor treatment adherence and tolerance, but few studies have examined the psychosocial determinants of treatment adherence and outcomes. Methods. Chart abstracted and survey data were collected on 72 HIV patients who had received pegylated interferon and ribavirin to assess correlates of treatment adherence, completion, and sustained virologic response (SVR. Results. Nearly half (46% the sample had active psychiatric problems and 13% had illicit drug use at treatment onset; 28% reported <100% treatment adherence, 38% did not complete treatment (mostly due to virologic nonresponse, and intent to treat SVR rate was 49%. Having a psychiatric diagnosis was associated with nonadherence, while better HCV adherence was associated with both treatment completion and SVR. Conclusions. Good mental health may be an indicator of HCV treatment adherence readiness, which is in turn associated with treatment completion and response, but further research is needed with new HCV treatments emerging.

  2. Multiparametric analyses of human PBMCs loaded ex vivo with a candidate idiotype vaccine for HCV-related lymphoproliferative disorders.

    Directory of Open Access Journals (Sweden)

    Annacarmen Petrizzo

    Full Text Available Hepatitis C virus (HCV has been identified as one of the major risk factors for type II mixed cryoglobulinemia (MC, during the clinical evolution of chronic hepatitis, which may lead to development of B cell non-Hodgkin's lymphoma (NHL. We have previously shown that the candidate idiotype vaccine, based on the IGKV3-20 light chain protein, is able to induce activation and maturation of circulating antigen presenting cells (APCs in both HCV-positive and HCV-negative healthy control subjects, with production of Th2-type cytokines. Here, the effect of the recombinant IGKV3-20 protein on human peripheral blood mononuclear cells (PBMCs from HCV-positive subjects, with known blood levels of cryoglobulins, is shown via gene expression profiling analysis combined to multiparameter flow cytometry and multiplex analyses of cytokines.

  3. Evaluation of cellular responses for a chimeric HBsAg-HCV core DNA vaccine in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Maryam Yazdanian

    2015-01-01

    Conclusion: Fusion of HBsAg to HCVcp in the context of a DNA vaccine modality could augment Th1-oriented cellular and CTL responses toward a protective epitope, comparable to that of HCVcp (subunit HCV vaccine immunization.

  4. 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.

  5. Prophylactic and Therapeutic Vaccination against Hepatitis C Virus (HCV: Developments and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Marian E. Major

    2009-08-01

    Full Text Available Studies in patients and chimpanzees that spontaneously clear Hepatitis C Virus (HCV have demonstrated that natural immunity to the virus is induced during primary infections and that this immunity can be cross protective. These discoveries led to optimism regarding prophylactic HCV vaccines and a number of studies in the chimpanzee model have been performed, all of which resulted in modified infections after challenge but did not always prevent persistence of the virus. Therapeutic vaccine strategies have also been pursued in an effort to reduce the costs and side effects associated with anti-viral drug treatment. This review summarizes the studies performed thus far in both patients and chimpanzees for prophylactic and therapeutic vaccination, assesses the progress made and future perspectives.

  6. 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.

  7. New pandemics: HIV and AIDS, HCV and chronic hepatitis, Influenza virus and flu

    Science.gov (United States)

    Gatignol, Anne; Dubuisson, Jean; Wainberg, Mark A; Cohen, Éric A; Darlix, Jean-Luc

    2007-01-01

    New pandemics are a serious threat to the health of the entire world. They are essentially of viral origin and spread at large speed. A meeting on this topic was held in Lyon, France, within the XIXth Jacques Cartier Symposia, a series of France-Québec meetings held every year. New findings on HIV and AIDS, on HCV and chronic hepatitis, and an update on influenza virus and flu were covered during this meeting on December 4 and 5, 2006. Aspects of viral structure, virus-host interactions, antiviral defenses, drugs and vaccinations, and epidemiological aspects were discussed for HIV and HCV. Old and recent data on the flu epidemics ended this meeting. PMID:17270043

  8. New pandemics: HIV and AIDS, HCV and chronic hepatitis, Influenza virus and flu

    Directory of Open Access Journals (Sweden)

    Cohen Éric A

    2007-02-01

    Full Text Available Abstract New pandemics are a serious threat to the health of the entire world. They are essentially of viral origin and spread at large speed. A meeting on this topic was held in Lyon, France, within the XIXth Jacques Cartier Symposia, a series of France-Québec meetings held every year. New findings on HIV and AIDS, on HCV and chronic hepatitis, and an update on influenza virus and flu were covered during this meeting on December 4 and 5, 2006. Aspects of viral structure, virus-host interactions, antiviral defenses, drugs and vaccinations, and epidemiological aspects were discussed for HIV and HCV. Old and recent data on the flu epidemics ended this meeting.

  9. Efficacy and tolerability of telaprevir (TVR-based triple therapy in HIV/HCV-coinfected patients

    Directory of Open Access Journals (Sweden)

    Ignacio De Los Santos

    2014-11-01

    Full Text Available Introduction: Clinical trials (CT on triple therapy against HCV infection in HIV-infected patients including TVR plus pegylated interferon and ribavirin (PR have reported considerably higher response rates than with PR alone. This study was aimed to evaluate the efficacy and safety of triple therapy including TVR in HIV/HCV-coinfected patients in real-life conditions. Materials and Methods: HIV/HCV genotype 1 patients seen at four Hospitals in Madrid who received therapy including TVR plus PR for at least two weeks were included. The response was evaluated during treatment, and sustained viral response (SVR was evaluated 12 and 24 weeks after the end of the treatment. Results: Fifty-eight patients have been included; 79% male, median age 48 y.o.; 38% were IL28B rs12979860 genotype CT or TT, 58.6% of patients presented cirrhosis and 24.1% presented fibrosis F3. Infection with genotype 1a was observed in 53.4% of patients. Median baseline HCV-RNA was 3,282,263 IU/mL (77.5% had >800,000 IU/mL. The most commonly used antiretroviral (ARV drugs were tenofovir/emtricitabine [36 (62% patients], etravirine [21 (36% patients], abacavir/lamivudine [18 (31% patients], boosted protease inhibitors [16 (27.5% patients] and raltegravir [12 (20.6% patients]. Of the 42 (72.4% patients who had received previous HCV treatment, 13.7% were null responders, 25.8% were partial responders and 31% had relapsed. In an ITT approach, proportions of patients with undetectable HCV RNA were 67.8% (38/56 at TW4, 83.3% (40/48 at TW12, 80% (36/45 at TW24, 79.4% at TW36 (31/39 and 72% (26/36 at TW48. Fifteen (25.8% patients discontinued HCV therapy [8 (13.8% because they fulfilled stopping rules, 5 (8.6% individuals due to adverse events and 2 (3.4% were lost to follow-up]. Rash associated with TVR (grade 1 was observed in two cases (3.4% and all the patients showed anaemia at some point of treatment. In an analysis by ITT in the 31 patients who had a 60 week follow-up after

  10. DNA immunization with fusion genes containing HCV core region and HBV core region

    Institute of Scientific and Technical Information of China (English)

    杨莉; 刘晶; 孔玉英; 汪垣; 李光地

    1999-01-01

    The eucaryotic expression plasmids were constructed to express the complete (HCc191) or the truncated (HCc69 and HCc40) HCV core genes, solely or fused with the HBV core gene (HBc144). These constructions were transiently expressed in COS cells under the control of the CMV promoter. The antigenicity of HBc and HCc could be detected in the expression products by ELISA and Western blot. The mice immunized with these expression plasmids efficiently produced the anti-HCc antibodies, and also anti-HBc antibodies when the plasmids contained the fusion genes. In addition, the antibodies induced by the fusion genes were more persistent than those induced by the non-fusion HCV core genes. These indicate that the fusion of HCc genes to HBc gene is in favor of the immunogenicity of HCc, while the immunogenicity of HBc is not affected.

  11. Biochemical and radio-immunological studies on HCV-induced liver fibrosis

    International Nuclear Information System (INIS)

    Hepatitis C virus infection is now becoming a common health problem in Egypt. Liver biopsy is the gold standard for this diagnosis. However, liver biopsy is invasive and is associated with complications with chronic hepatitis C patients. There is a clinical need for noninvasive measurement of liver fibrosis. Noninvasive bio markers such as Collagen III was identified in serum samples of patients with HCV induced liver fibrosis at 70 kDa using SDS-PAGE and western blot, measured by ELISA and purified using electro elution . Hyaluronic acid also can be used to differentiate between liver fibrosis patients and healthy individuals using radioimmunoassay .we have developed noninvasive diagnosis that can be applied to patients who either have contraindications or refuse liver biopsy for the management of their HCV infection.

  12. A small yeast RNA inhibits HCV IRES mediated translation and inhibits replication of poliovirus in vivo

    Institute of Scientific and Technical Information of China (English)

    Xue-Song Liang; Jian-Qi Lian; Yong-Xing Zhou; Qing-He Nie; Chun-Qiu Hao

    2003-01-01

    AIM: To investigate the anti-virus infection activity of internal ribosome entry site (IRES) specific inhibitor RNA (IRNA).METHODS: IRNA eukaryotic vector pcRz-IRNA or mIRNA eukaryotic vector pcRz-mIRNA was tansfected into human hepatocarcinoma cells (HHCC), then selected with neomycin G418 for 4 to 8 weeks, and then infected with polio virus vaccinas line. The cytopethogenesis effect was investigated and the cell extract was collected. At last the polio virus titer of different cells was determined by plaque assay.RESULTS: Constitutive expression of IRNA was not detrimental to cell growth. HCV IRES-mediated capindependent translation was markedly inhibited in cells constitutively expressing IRNA compared to control hepatoma cells. However, cap-dependent translation was not significantly affected in these cell line. Additionally, HHCC cells constitutively expressing IRNA became refractory to infection of polio virus.CONCLUSION: IRES specific IRNA can inhibit HCV IRES mediated translation and poliovirus replication.

  13. The HCV Non-Nucleoside Inhibitor Tegobuvir Utilizes a Novel Mechanism of Action to Inhibit NS5B Polymerase Function

    OpenAIRE

    Hebner, Christy M.; Han, Bin; Brendza, Katherine M.; Nash, Michelle; Sulfab, Maisoun; Tian, Yang; Hung, Magdeleine; Fung, Wanchi; Vivian, Randall W.; Trenkle, James; Taylor, James; Bjornson, Kyla; Bondy, Steven; Liu, Xiaohong; Link, John

    2012-01-01

    Tegobuvir (TGV) is a novel non-nucleoside inhibitor (NNI) of HCV RNA replication with demonstrated antiviral activity in patients with genotype 1 chronic HCV infection. The mechanism of action of TGV has not been clearly defined despite the identification of resistance mutations mapping to the NS5B polymerase region. TGV does not inhibit NS5B enzymatic activity in biochemical assays in vitro, suggesting a more complex antiviral mechanism with cellular components. Here, we demonstrate that TGV...

  14. Personality disorders do not affect treatment outcomes for chronic HCV infection in Spanish prisoners: the Perseo study

    OpenAIRE

    Marco, Andrés; Antón, José J.; Trujols, Joan; Saíz de la Hoya, Pablo; Juan, José; Faraco, Inmaculada; Caylà, Joan A; ,

    2015-01-01

    Background The link between infection with hepatitis C virus (HCV) and personality disorders (PD) has not been investigated in detail. The aim of this study was to compare the effectiveness of HCV treatment in prisoners with and without PD. Methods We performed a prospective multicentre study in inmates from 25 Spanish prisons who had been treated with pegylated interferon alfa-2a plus ribavirin in 2011. PD diagnosis was based on the Personality Diagnostic Questionnaire-4+. We calculated adju...

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

    Science.gov (United States)

    Alves, Camila Fernanda da Silveira; Grott, Camila Schultz; Lunge, Vagner Ricardo; Béria, Jorge Umberto; Tietzmann, Daniela Cardoso; Stein, Airton Tetelbom; Simon, Daniel

    2016-01-01

    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. PMID:27560987

  16. Confirm the HCV NS5A protein interaction with aconitase 1%HCV NS5A结合蛋白顺乌头酸酶1的验证研究

    Institute of Scientific and Technical Information of China (English)

    王晓杰; 相久全; 韩乐强; 张锦前; 成军

    2011-01-01

    Objective To screen proteins of human liver cDNA library interacting with HCV NS5A and confirm the interaction between HCV N55A protein and aconitate 1 protein.Methods Yeast two hybrid was performed by mating AH109 ( HCV NS5A) with Y187 ( liver cDNA lihrary of human) .The interacted proteins with HCV NS5A were screened from the library.The aconitate 1 gene was amplified at first.The expression vectors of aconitate 1 were constructed.Then the interaction between HCV N55A protein and Homo sapiens aconitate 1 protein was confirmed using co-imruunoprecipitation and mammalian two hybrid experiment.Results The eukaryotic expression vectors of aconitate 1 were constructed.These results showed that Homo sapiens aconitate 1 protein interacted with HCV NS5A protein by co-immunoprecipitation and mammalian two hybrids experiment Conclusion HCV NS5A and Homo sapiens aconitate 1 protein can interact in HepCJ2 cells.%目的 筛选人肝脏cDNA文库中与HCV NS5A的结合蛋白基因,验证其中顺乌头酸酶1与HCV NS5A的相互作用.方法 应用酵母双杂交系统3筛选人肝脏cDNA文库中的HCV NS5A结合蛋白基因,应用哺乳动物双杂交及免疫共沉淀技术验证其中顺乌头酸酶1蛋白与HCV NS5A之间的相瓦作用.结果 成功筛选出人肝脏cD-NA文库中与HCV NS5A存在相瓦作用的蛋白基因,哺乳动物双杂交及免疫共沉淀实验结果 证实HCV NS5A与顺乌头酸酶1蛋白在HepG2细胞内存在相互作用.结论 本实验成功筛选人肝脏cDNA文库中的HCV NS5A结合蛋白基因,并且在体外水平即细胞内证实HCV NS5A与其中的顺乌头酸酶1蛋白之间的相互作用,为进一步细胞内及体内的糖、脂类代谢等功能研究奠定基础.

  17. dsRNA-Dependent Protein Kinase PKR and its Role in Stress, Signaling and HCV Infection

    Directory of Open Access Journals (Sweden)

    Eliane F. Meurs

    2012-10-01

    Full Text Available The double-stranded RNA-dependent protein kinase PKR plays multiple roles in cells, in response to different stress situations. As a member of the interferon (IFN‑Stimulated Genes, PKR was initially recognized as an actor in the antiviral action of IFN, due to its ability to control translation, through phosphorylation, of the alpha subunit of eukaryotic initiation factor 2 (eIF2a. As such, PKR participates in the generation of stress granules, or autophagy and a number of viruses have designed strategies to inhibit its action. However, PKR deficient mice resist most viral infections, indicating that PKR may play other roles in the cell other than just acting as an antiviral agent. Indeed, PKR regulates several signaling pathways, either as an adapter protein and/or using its kinase activity. Here we review the role of PKR as an eIF2a kinase, its participation in the regulation of the NF-kB, p38MAPK and insulin pathways, and we focus on its role during infection with the hepatitis C virus (HCV. PKR binds the HCV IRES RNA, cooperates with some functions of the HCV core protein and may represent a target for NS5A or E2. Novel data points out for a role of PKR as a pro-HCV agent, both as an adapter protein and as an eIF2a-kinase, and in cooperation with the di-ubiquitin-like protein ISG15. Developing pharmaceutical inhibitors of PKR may help in resolving some viral infections as well as stress-related damages.

  18. Disturbances of Tryptophan Metabolism and Risk of Depression in HCV Patients Treated with IFN-Alpha

    OpenAIRE

    Oxenkrug, GF; Turski, WA; Zgrajka, W; Weinstock, JV; Ruthazer, R.; P. Summergrad

    2014-01-01

    Depression is a common side-effect of interferon (IFN)-alpha treatment of hepatitis C virus (HCV) infection and melanoma. Disturbances of tryptophan (TRP) metabolism might contribute to development of IFN-alpha–associated depression due to IFN-alpha-induced activation of indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme of TRP–kynurenine (KYN) metabolism. The increased frequency of high producer (T) allele of IFN-gamma (IFNG) (+874) gene, that encodes IFNG production, in depressed pat...

  19. HIV and HCV discordant injecting partners and their association to drug equipment sharing

    OpenAIRE

    DE, PRITHWISH; Cox, Joseph; Boivin, Jean-François; Robert W Platt; Jolly, Ann M.; Alexander, Paul E

    2009-01-01

    Our objective was to examine the association between HIV and HCV discordant infection status and the sharing of drug equipment by injection drug users (IDUs). IDUs were recruited from syringe exchange and methadone treatment programmes in Montreal, Canada. Characteristics of participants and their injecting partners were elicited using a structured questionnaire. Among 159 participants and 245 injecting partners, sharing of syringes and drug preparation equipment did not differ between concor...

  20. Inflammatory pseudotumor of the liver in a patient with congenital granulocytopenia and HCV infection

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, G. E-mail: ragsne@uniklink-saarland.de; Fries, P.; Samaras, P.; Remberger, K.; Uder, M.; Kramann, B

    2003-12-01

    Inflammatory pseudotumor (IPT) of the liver is a rare pathologic lesion. Although IPTs within the liver shows spontaneous regression, these lesions are frequently misdiagnosed as malignant on the basis of the clinical manifestation and the results of diagnostic imaging. With special regard to magnetic resonance imaging (MRI), differential diagnosis such as hepatocellular or cholangiocellular carcinoma (HCC/CCC) as well as regenerative liver lesions are discussed in a case of IPT with concomitant hepatitis C virus (HCV) infection and congenital granulocytopenia.

  1. Status of Health related Quality of life between HBV and HCV Patients of Pakistan

    OpenAIRE

    Awan, Masood Sarwar; Waqas, Muhammad; Ali, Mumtaz; Aslam, Muhammad Amir

    2011-01-01

    The aim of the study is to explore the factors those differentiate health related quality of life (HRQOL) among hepatitis B (HBV) and hepatitis C (HCV) patients. Different public and private hospitals of Sargodha district were visited and 120 patients of hepatitis B and C were interviewed. World health related quality of life-BREF (WHOQOL-BREF) questionnaire was used to construct HRQOL instrument. Multiple regression analysis was performed to observe the collision of demographic, medica...

  2. Seroprevalences of HBV, HCV and HIV among Children who examined Before Elective Surgery in Mardin province

    OpenAIRE

    Tekin A et al.

    2011-01-01

    Objectives: The aim of this study was to investigate the seroprevalence of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) among children who examined before elective surgery in Mardin province. Materials and Methods: Between 01 November 2008 and 30 April 2010, a total of 556 patients aged 0–16 years, who planned to be operated, were investigated for viral hepatitis seroprevalences in the Mardin Women and Pediatrics Hospital. Children’s blood samples w...

  3. Prevalence and Correlates of HCV, HVB, and HIV Infection among Prison Inmates and Staff, Hungary

    OpenAIRE

    Tresó, Bálint; Barcsay, Erzsébet; Tarján, Anna; Horváth, Gergely; Dencs, Ágnes; Hettmann, Andrea; Csépai, Mária Magdolna; Győri, Zoltán; Rusvai, Erzsébet; Takács, Mária

    2011-01-01

    The aim of this national, multicenter, cross-sectional study was to assess the prevalence of hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency viruses (HIV) among prisoners, and to identify related risk behaviors including injection drug use. Overall, 4,894 inmates from 20 prisons were enrolled. To have a comparison group, prison staff were also asked to take part. Altogether, 1,553 of the 4,894 inmates from seven prisons completed a questionnaire on risk behaviors. According t...

  4. Monocyte activation in HIV/HCV coinfection correlates with cognitive impairment.

    Directory of Open Access Journals (Sweden)

    Hans Rempel

    Full Text Available Coinfection with human immunodeficiency virus (HIV and hepatitis C virus (HCV challenges the immune system with two viruses that elicit distinct immune responses. Chronic immune activation is a hallmark of HIV infection and an accurate indicator of disease progression. Suppressing HIV viremia by antiretroviral therapy (ART effectively prolongs life and significantly improves immune function. HIV/HCV coinfected individuals have peripheral immune activation despite effective ART control of HIV viral load. Here we examined freshly isolated CD14 monocytes for gene expression using high-density cDNA microarrays and analyzed T cell subsets, CD4 and CD8, by flow cytometry to characterize immune activation in monoinfected HCV and HIV, and HIV-suppressed coinfected subjects. To determine the impact of coinfection on cognition, subjects were evaluated in 7 domains for neuropsychological performance, which were summarized as a global deficit score (GDS. Monocyte gene expression analysis in HIV-suppressed coinfected subjects identified 43 genes that were elevated greater than 2.5 fold. Correlative analysis of subjects' GDS and gene expression found eight genes with significance after adjusting for multiple comparisons. Correlative expression of six genes was confirmed by qPCR, five of which were categorized as type 1 IFN response genes. Global deficit scores were not related to plasma lipopolysaccharide levels. In the T cell compartment, coinfection significantly increased expression of activation markers CD38 and HLADR on both CD4 and CD8 T cells but did not correlate with GDS. These findings indicate that coinfection is associated with a type 1 IFN monocyte activation profile which was further found to correlate with cognitive impairment, even in subjects with controlled HIV infection. HIV-suppressed coinfected subjects with controlled HIV viral load experiencing immune activation could benefit significantly from successful anti-HCV therapy and may be

  5. Genetic analyses reveal a role for vitamin D insufficiency in HCV-associated hepatocellular carcinoma development.

    Directory of Open Access Journals (Sweden)

    Christian M Lange

    Full Text Available BACKGROUND: Vitamin D insufficiency has been associated with the occurrence of various types of cancer, but causal relationships remain elusive. We therefore aimed to determine the relationship between genetic determinants of vitamin D serum levels and the risk of developing hepatitis C virus (HCV-related hepatocellular carcinoma (HCC. METHODOLOGY/PRINCIPAL FINDINGS: Associations between CYP2R1, GC, and DHCR7 genotypes that are determinants of reduced 25-hydroxyvitamin D (25[OH]D3 serum levels and the risk of HCV-related HCC development were investigated for 1279 chronic hepatitis C patients with HCC and 4325 without HCC, respectively. The well-known associations between CYP2R1 (rs1993116, rs10741657, GC (rs2282679, and DHCR7 (rs7944926, rs12785878 genotypes and 25(OHD3 serum levels were also apparent in patients with chronic hepatitis C. The same genotypes of these single nucleotide polymorphisms (SNPs that are associated with reduced 25(OHD3 serum levels were found to be associated with HCV-related HCC (P = 0.07 [OR = 1.13, 95% CI = 0.99-1.28] for CYP2R1, P = 0.007 [OR = 1.56, 95% CI = 1.12-2.15] for GC, P = 0.003 [OR = 1.42, 95% CI = 1.13-1.78] for DHCR7; ORs for risk genotypes. In contrast, no association between these genetic variations and liver fibrosis progression rate (P>0.2 for each SNP or outcome of standard therapy with pegylated interferon-α and ribavirin (P>0.2 for each SNP was observed, suggesting a specific influence of the genetic determinants of 25(OHD3 serum levels on hepatocarcinogenesis. CONCLUSIONS/SIGNIFICANCE: Our data suggest a relatively weak but functionally relevant role for vitamin D in the prevention of HCV-related hepatocarcinogenesis.

  6. Correlations of folic acid, vitamin B12, homocysteine, and thrombopoietin to platelet count in HCV infection

    OpenAIRE

    Somayh S. Eissa; Olfat M. Hendy; Fatma Younis; Aziza K. Omar Samy; Ayat R. Abdallah; Laila A. Ahmed

    2012-01-01

    IntroductionThe platelet count is known to decrease in proportion to the advancement of the stage of liver disease in chronic hepatitis C (CHC) viral infection. The platelet count is currently used as an index for fibrosis staging. The pathophysiology of thrombocytopenia (TCP) in patients with hepatitis C virus (HCV) infection is not completely understood. PurposeThis work aimed to study the correlations of folic acid (FA), vitamin B12 (Vit B12), homocysteine (Hcy), and thrombopoietin to t...

  7. HIV, HBV, and HCV molecular epidemiology among trans (transvestites, transsexuals, and transgender) sex workers in Argentina.

    Science.gov (United States)

    Carobene, Mauricio; Bolcic, Federico; Farías, María Sol Dos Ramos; Quarleri, Jorge; Avila, María Mercedes

    2014-01-01

    Commercial sex work is frequent among male-to-female transvestites, transsexuals and transgenders in Argentina, leading to high susceptibility to HIV, HBV, and HCV among other sexually transmitted infections. In a global context of scarce data on the trans sex workers population, this study was aimed to study the genomic characterization of these viruses. Plasma presence of HIV, HBV, and HCV genomic material was evaluated in samples from 273 trans sex workers. Genomic sequences of HIV-gag, pol, and vif-vpu genes, HBV-S gene, and HCV-5'UT and NS5B genes were obtained. Molecular characterization involved phylogenetic analysis and several in silico tools. Resistance-associated mutations in HIV and HBV pol genes were also analyzed. The HIV genomic characterization in 62 trans sex workers samples showed that 54.8% of the isolates corresponded to BF intersubtype recombinants, and 38.7% to subtype B. The remaining were classified as subtypes C (4.8%) and A (1.6%). HBV and HCV co-infection prevalence among HIV positive trans sex workers yielded rates of 3.2% and 6.5% respectively. Drug resistance-associated mutations were found in 12/62 (19%) HIV pol sequences, but none among HBV. Based on phylogenetic relationships, HIV isolates characterized as subtypes BF and B appeared intermingled with those from other high-risk groups. Despite trans sex workers declared not to have received antiviral treatment, complex drug resistance-associated mutation patterns were found in several HIV isolates. Planned prevention, screening, and treatment are needed to reduce further transmission and morbidity. PMID:24123155

  8. Composition of inflammatory infiltrate and its correlation with HBV/HCV antigen expression

    Institute of Scientific and Technical Information of China (English)

    Bozena Walewska-Zielecka; Kazimierz Madalinski; Joanna Jablonska; Paulina Godzik; Joanna Cielecka-Kuszyk; Bogumila Litwinska

    2008-01-01

    AIM: To study the composition of liver inflammatory infiltrate in biopsy material from patients chronically infected with hepatotropic viruses and to evaluate the correlation of inflammatory infiltrate with hepatitis B virus (HBV) and hepatitis C virus (HCV) viral antigen expression in chronic B and C hepatitis.METHODS: The phenotype of inflammatory cells was evaluated by the EnVision system, using a panel of monoclonal antibodies. HBV and HCV antigens were detected with the use of monoclonal anti-HBs, poly-clonal anti-HBc and anti-HCV antibodies, respectively.RESULTS: The cellular composition of liver inflammatory infiltrate was similar in the patients with B and C hepatitis: ~50%-60% of cells were T helper lymphooltes. Approximately 25% were T cytotoxic lymphocytes; B lymphocytes comprised 15% of inflammatory infiltrate; other cells, including NK, totalled 10%. Expression of HLA antigens paralleled inflammatory activity. Portal lymphadenoplasia was found more often in hepatitis C (54.5%) than in hepatitis B (30.6%). Expression of HB-cAg was found more often in chronic B hepatitis of moderate or severe activity. Overall inflammatory activity in HBV-infected cases did not correlate with the intensity of HBsAg expression in hepatooltes. Inflammatory infiltrates accompanied the focal expression of HCV anti-gens. A direct correlation between antigen expression and inflammatory reaction in situ was noted more often in hepatitis C than B.CONCLUSION: Irrespective of the etiology and activity of hepatitis, components of the inflammatory infiltrate in liver were similar. Overall inflammatory activity did not correlate with the expression of HBsAg and HCVAg; HBcAg expression, however, accompanied chronic hepatitis B of moderate and severe activity.

  9. Are the Real HCV Infection Features in Iranian Patients the Same As What Is Expected?

    OpenAIRE

    Seyed-Moayed Alavian

    2005-01-01

    Hepatitis Monthly issue 7 contained four clinical trials of pegylated interferon (Peg- IFN) plus ribavirin for Iranian patients with chronic hepatitis C infection conducted in four various centers(1-4). Apart from one trial(2), which enrolled only patients with inherited bleeding disorders, three others enrolled heterogeneous HCV infected populations. However, reported sustained virologic response (SVR) rate was varied from 50% to 78% in these studies. This wide SVR range might make difficult...

  10. Adiponectin changes in HCV-Genotype 4: relation to liver histology and response to treatment

    OpenAIRE

    Derbala, M.; Rizk, N.; Al-Kaabi, S.; Amer, A; Shebl, F.; Al Marri, A.; Aigha, I.; Alyaesi, D.; Mohamed, H.; Aman, H; Basem, N.

    2009-01-01

    Summary.  Recently, attention has been focussed on adiponectin and its changes in different types of chronic liver disease. Its relation to hepatic fibrosis and insulin resistance in post-hepatitis liver disease is not clear. The aim of this study was to clarify the adiponectin changes in genotype 4 hepatitis C virus (HCV)-infected patient in relation to liver histology and insulin resistance, and its usefulness as a predictor of hepatic fibrosis and response to treatment. Total adiponectin a...

  11. Prevalence of HIV-1/2, HTLV-I/II, hepatitis B virus (HBV, hepatitis C virus (HCV, Treponema pallidum and Trypanosoma cruzi among prison inmates at Manhuaçu, Minas Gerais State, Brazil Prevalência do HIV-1/2, do HTLV-I/II, do vírus da hepatite B (HBV e C (HCV, do Treponema pallidum e do Trypanosoma cruzi entre presidiários em Manhuaçu, Minas Gerais, Brasil

    Directory of Open Access Journals (Sweden)

    Bernadette Corrêa Catalan-Soares

    2000-02-01

    Full Text Available The purpose of this study was to determine the seroprevalence of human immunodeficiency virus (HIV-1/2, human T-cell lymphotropic virus (HTLV-I/II, hepatitis B virus (HBV, hepatitis C virus (HCV, Treponema pallidum and Trypanosoma cruzi among 63 male prisoners in Manhuaçu, Minas Gerais, Brazil and to compare this with data from eligible blood donors. The positive results were as follows: 11/63 (17.5% for HBV, 5/63 (7.4% for syphilis, 4/63 (6.3% for HCV, 3/63 (4.8% for Chagas' disease, 2/63 (3.2% for HIV-1/2 and 1/63 (1.6% for HTLV-I/II. The seroprevalence in prisoners was higher than among blood donors, mainly for antibodies to HIV-1/2, HCV and HBV. This is probably due to low social economic level, illiteracy, higher proportion with a prior history of intravenous drug use and/or unsafe sexual behavior. Therefore, these prisoners constitute a high risk group and routine screening and counseling are recommended.O objetivo deste estudo foi determinar a oroprevalência do vírus da imunodeficiência humana (HIV-1/2, do vírus linfotrópico humano (HTLV-I/II, da hepatite B (HBV, da hepatitis C (HCV, do Treponema pallidum e do Trypanosoma cruzi em 63 presidiários do sexo masculino em Manhuaçu, Minas Gerais, Brasil e comparar com resultados de doadores de sangue. Os resultados positivos foram: 11/63 (17,5% para HBV, 5/63 (7,4% para sífilis, 4/63 (6,3% para HCV, 3/63 (4,8% para doença de Chagas, 2/63 (3,2% para HIV-1/2 e 1/63 (1,6% para HTLV-I/II. A soroprevalência em prisioneiros foi mais alta que entre doadores de sangue, principalmente para anticorpos anti-HIV-1/2, HCV e HBV. Isso se deve provavelmente ao baixo nível socio-econômico e de escolaridade, proporção elevada de história pregressa de uso de drogas endovenosas e/ou comportamento sexual de risco. Concluímos que prisioneiros constituem um grupo de alto risco para essas doenças e testes de triagem e aconselhamento são recomendados como rotina no ambiente carcerário.

  12. Vitamin D level and vitamin D receptor genetic variations contribute to HCV infection susceptibility and chronicity in a Chinese population.

    Science.gov (United States)

    Wu, Mengping; Yue, Ming; Huang, Peng; Zhang, Yun; Xie, Chaonan; Yu, Rongbin; Li, Jun; Wang, Jie

    2016-07-01

    Vitamin D and vitamin D receptor (VDR) are involved in multiple immune-mediated disorders including chronic hepatitis C virus (HCV) infection. The aim of this study was to determine the association between plasma vitamin D level, VDR genetic polymorphisms and risk of HCV infection susceptibility and chronicity. Seven single nucleotide polymorphisms (SNPs) in VDR gene were genotyped and plasma 25-hydroxyvitamin D [25(OH)D] levels were measured in a Han Chinese population of 898 HCV persistent infection cases, 558 spontaneous clearance subjects and 1136 uninfected controls with high risk of HCV infection. In this case-control study, the average plasma 25(OH)D level in persistent infection patients was significantly lower than that in spontaneous clearance cases (P=0.039) and controls (P=0.005). Logistic analyses indicated that rs7975232-C, rs2239185-T and rs11574129-T alleles were significantly associated with a decreased risk of HCV infection susceptibility (all PBonferroniVDR variants (rs7975232-C, rs2239185-T and rs11574129-T) might contribute to a decreased susceptibility to HCV infection in a high-risk Chinese population. PMID:27063396

  13. Receptor complementation and mutagenesis reveal SR-BI as an essential HCV entry factor and functionally imply its intra- and extra-cellular domains.

    Directory of Open Access Journals (Sweden)

    Marlène Dreux

    2009-02-01

    Full Text Available HCV entry into cells is a multi-step and slow process. It is believed that the initial capture of HCV particles by glycosaminoglycans and/or lipoprotein receptors is followed by coordinated interactions with the scavenger receptor class B type I (SR-BI, a major receptor of high-density lipoprotein (HDL, the CD81 tetraspanin, and the tight junction protein Claudin-1, ultimately leading to uptake and cellular penetration of HCV via low-pH endosomes. Several reports have indicated that HDL promotes HCV entry through interaction with SR-BI. This pathway remains largely elusive, although it was shown that HDL neither associates with HCV particles nor modulates HCV binding to SR-BI. In contrast to CD81 and Claudin-1, the importance of SR-BI has only been addressed indirectly because of lack of cells in which functional complementation assays with mutant receptors could be performed. Here we identified for the first time two cell types that supported HCVpp and HCVcc entry upon ectopic SR-BI expression. Remarkably, the undetectable expression of SR-BI in rat hepatoma cells allowed unambiguous investigation of human SR-BI functions during HCV entry. By expressing different SR-BI mutants in either cell line, our results revealed features of SR-BI intracellular domains that influence HCV infectivity without affecting receptor binding and stimulation of HCV entry induced by HDL/SR-BI interaction. Conversely, we identified positions of SR-BI ectodomain that, by altering HCV binding, inhibit entry. Finally, we characterized alternative ectodomain determinants that, by reducing SR-BI cholesterol uptake and efflux functions, abolish HDL-mediated infection-enhancement. Altogether, we demonstrate that SR-BI is an essential HCV entry factor. Moreover, our results highlight specific SR-BI determinants required during HCV entry and physiological lipid transfer functions hijacked by HCV to favor infection.

  14. Increased expression and dysregulated association of restriction factors and type I interferon in HIV, HCV mono- and co-infected patients.

    Science.gov (United States)

    Zhu, Jia-Wu; Liu, Feng-Liang; Mu, Dan; Deng, De-Yao; Zheng, Yong-Tang

    2016-06-01

    Host restriction factors and type I interferon are important in limiting HIV and HCV infections, yet the role of HIV, HCV mono- and co-infection in regulating these antiviral genes expression is not clear. In this study, we measured the levels of TRIM5α, TRIM22, APOBEC3G, and IFN-α, -β mRNA expression in peripheral blood mononuclear cells of 43 HIV mono-infected, 70 HCV mono-infected and 64 HIV/HCV co-infected patients along with 98 healthy controls. We also quantified HIV and HCV viral loads in mono- and co-infected patients. The results showed that HCV, HIV mono- and co-infection differentially increased TRIM22, APOBEC3G, and IFN-α, -β mRNA expression while the mRNA expression of TRIMα was upregulated only by HCV-mono infection. HIV/HCV co-infection was associated with higher viral load, compared to either HIV or HCV mono-infection. Additionally, we showed TRIMα and TRIM22 positively correlated with IFN-α, -β, which could be dysregulated by HIV, HCV mono- and co-infection. Furthermore, we found TRIM22 negatively correlated with HCV viral load in mono-infected patients and APOBEC3G positively correlated with HCV viral load in co-infected patients. Collectively, our findings suggest the potential role of restriction factors in restricting HIV, HCV mono- and co-infection in vivo, which appears to be a therapeutic target for potential drug discovery. J. Med. Virol. 88:987-995, 2016. © 2015 Wiley Periodicals, Inc. PMID:26519943

  15. 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. PMID:27125573

  16. A Framework for Prediction of Response to HCV Therapy Using Different Data Mining Techniques

    Directory of Open Access Journals (Sweden)

    Enas M. F. El Houby

    2014-01-01

    Full Text Available Hepatitis C which is a widely spread disease all over the world is a fatal liver disease caused by Hepatitis C Virus (HCV. The only approved therapy is interferon plus ribavirin. The number of responders to this treatment is low, while its cost is high and side effects are undesirable. Treatment response prediction will help in reducing the patients who suffer from the side effects and high costs without achieving recovery. The aim of this research is to develop a framework which can select the best model to predict HCV patients’ response to the treatment of HCV from clinical information. The framework contains three phases which are preprocessing phase to prepare the data for applying Data Mining (DM techniques, DM phase to apply different DM techniques, and evaluation phase to evaluate and compare the performance of the built models and select the best model as the recommended one. Different DM techniques had been applied which are associative classification, artificial neural network, and decision tree to evaluate the framework. The experimental results showed the effectiveness of the framework in selecting the best model which is the model built by associative classification using histology activity index, fibrosis stage, and alanine amino transferase.

  17. HVR1-mediated antibody evasion of highly infectious in vivo adapted HCV in humanised mice

    DEFF Research Database (Denmark)

    Prentoe, Jannick; Verhoye, Lieven; Velázquez Moctezuma, Rodrigo; Buysschaert, Caroline; Farhoudi, Ali; Wang, Richard; Alter, Harvey; Meuleman, Philip; Bukh, Jens

    2016-01-01

    of HCV from human liver chimeric mice infected with cell-culture-derived prototype genotype 2a recombinant J6/JFH1 or HVR1-deleted variant J6/JFH1ΔHVR1 identified adaptive mutations, which were analysed by reverse genetics in Huh7.5 and CD81-deficient S29 cells. The increased in vivo genomic......OBJECTIVE: HCV is a major cause of chronic liver disease worldwide, but the role of neutralising antibodies (nAbs) in its natural history remains poorly defined. We analysed the in vivo role of hypervariable region 1 (HVR1) for HCV virion properties, including nAb susceptibility. DESIGN: Analysis...... identified A876P-substitution resulted in a 4.7-fold increase in genomic stability. In vitro, NS2 substitutions enhanced infectivity 5-10-fold by increasing virus assembly. Mouse-derived mJ6/JFH1A876P and mJ6/JFH1ΔHVR1/A876P viruses displayed similar heterogeneous densities of 1.02-1.1 g/mL. Human liver...

  18. A Turbidity Test Based Centrifugal Microfluidics Diagnostic System for Simultaneous Detection of HBV, HCV, and CMV

    Directory of Open Access Journals (Sweden)

    Hung-Cheng Chang

    2015-01-01

    Full Text Available This paper presents a LAMP- (loop-mediated isothermal amplification- based lab-on-disk optical system that allows the simultaneous detection of hepatitis B virus, hepatitis C virus, and cytomegalovirus. The various flow stages are controlled in the proposed system using different balance among centrifugal pumping, Coriolis pumping, and the capillary force. We have implemented a servo system for positioning and speed control for the heating and centrifugal pumping. We have also successfully employed a polymer light-emitting diode section for turbidity detection. The easy-to-use one-click system can perform diagnostics in less than 1 hour.

  19. DCs Pulsed with Novel HLA-A2-Restricted CTL Epitopes against Hepatitis C Virus Induced a Broadly Reactive Anti-HCV-Specific T Lymphocyte Response

    OpenAIRE

    Zhongsheng Guo; Henghui Zhang; Huiying Rao; Dong Jiang; Xu Cong; Bo Feng(Zhejiang Institute of Modern Physics, Zhejiang University, 38 Zheda Road Hangzhou, 310027 P.R. China); Jianghua Wang; Lai Wei; Hongsong Chen

    2012-01-01

    OBJECTIVE: To determine the capacity of dendritic cells (DCs) loaded with single or multiple-peptide mixtures of novel hepatitis C virus (HCV) epitopes to stimulate HCV-specific cytotoxic T lymphocyte (CTL) effector functions. METHODS: A bioinformatics approach was used to predict HLA-A2-restricted HCV-specific CTL epitopes, and the predicted peptides identified from this screen were synthesized. Subsequent IFN-γ ELISPOT analysis detected the stimulating function of these peptides in peripher...

  20. Mechanism of HCV's resistance to IFN-α in cell culture involves expression of functional IFN-α receptor 1

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    Lamaze Christophe

    2011-07-01

    Full Text Available Abstract The mechanisms underlying the Hepatitis C virus (HCV resistance to interferon alpha (IFN-α are not fully understood. We used IFN-α resistant HCV replicon cell lines and an infectious HCV cell culture system to elucidate the mechanisms of IFN-α resistance in cell culture. The IFN-α resistance mechanism of the replicon cells were addressed by a complementation study that utilized the full-length plasmid clones of IFN-α receptor 1 (IFNAR1, IFN-α receptor 2 (IFNAR2, Jak1, Tyk2, Stat1, Stat2 and the ISRE- luciferase reporter plasmid. We demonstrated that the expression of the full-length IFNAR1 clone alone restored the defective Jak-Stat signaling as well as Stat1, Stat2 and Stat3 phosphorylation, nuclear translocation and antiviral response against HCV in all IFN-α resistant cell lines (R-15, R-17 and R-24 used in this study. Moreover RT-PCR, Southern blotting and DNA sequence analysis revealed that the cells from both R-15 and R-24 series of IFN-α resistant cells have 58 amino acid deletions in the extracellular sub domain 1 (SD1 of IFNAR1. In addition, cells from the R-17 series have 50 amino acids deletion in the sub domain 4 (SD4 of IFNAR1 protein leading to impaired activation of Tyk2 kinase. Using an infectious HCV cell culture model we show here that viral replication in the infected Huh-7 cells is relatively resistant to exogenous IFN-α. HCV infection itself induces defective Jak-Stat signaling and impairs Stat1 and Stat2 phosphorylation by down regulation of the cell surface expression of IFNAR1 through the endoplasmic reticulum (ER stress mechanisms. The results of this study suggest that expression of cell surface IFNAR1 is critical for the response of HCV to exogenous IFN-α.

  1. Comorbidades entre dependência química, distimia, HIV e HCV: relato de caso Comorbidity between addiction, dysthymia, HIV and HCV: case report

    Directory of Open Access Journals (Sweden)

    Vanessa Fabiane Machado Gomes Marsden

    2009-01-01

    Full Text Available INTRODUÇÃO: A comorbidade entre dependência química e doenças infectocontagiosas é bem conhecida, assim como a relação entre transtornos de humor e uso de substâncias. Entretanto, o transtorno distímico nestes pacientes recebe pouca atenção. Em parte, isso se justifica porque a realização do diagnóstico de distimia é mais difícil do que de outros transtornos do humor em razão do tempo de abstinência (2 anos necessário para o diagnóstico, tendo em vista que toxicodependentes apresentam diversas recaídas durante o curso de suas vidas. As infecções pelos vírus HIV e HCV, frequentemente associadas ao consumo injetável de substâncias, contribuem para alterações do estado mental e o próprio tratamento pode causar diversas flutuações no humor. RELATO DE CASO: O paciente é um homem de 40 anos de idade que apresenta comorbidade entre dependência química (heroína e álcool e distimia, complicada por recaídas, consumo injetável e status sorológico positivo aos vírus HIV-1 e HCV. CONCLUSÃO: Pacientes dependentes químicos com comorbidades psiquiátricas e infectocontagiosas são desafiadores no que tange diagnóstico, tratamento e definição de abordagens terapêuticas para os diferentes problemas apresentados. Investigar e abordar adequadamente, entretanto, traz diversos benefícios na qualidade de vida do indivíduo afetado, assim como potenciais benefícios financeiros.BACKGROUND: Comorbidity between chemical dependence and infectious diseases is well known, as is the relationship between mood disorders and substance misuse. Nevertheless, dysthymia in these patients is not well explored. That is partly justified since the diagnoses of dysthymia is more difficult than other mood disorders due to the abstinence time (2 years required for the diagnoses, and since addiction patients present several relapses during the course of their lifetimes. HIV and HCV infections, frequently associated to intravenous (IV drug use

  2. The Usefulness of Defining Rapid Virological Response by a Very Sensitive Assay (TMA) during Treatment of HCV Genotype 2/3 Infection

    DEFF Research Database (Denmark)

    Dalgard, Olav; Martinot-Peignoux, Michelle; Verbaan, Hans;

    2015-01-01

    and 24 weeks treatment to patients with rapid virological response (RVR) (n = 550). RVR was originally defined as HCV RNA <50 IU/ml at week 4. Patients with an available frozen plasma sample drawn at week 4 and with follow-up data week 24 post-treatment were included (n = 429). HCV-RNA was...... sensitivity for HCV RNA identifies patients at week 4 with high risk of virological relapse. We recommend that patients with genotype 3 and detectable HCV RNA at levels below 50 IU/ml do not receive truncated therapy with pegIFN and ribavirin....

  3. Staufen1 promotes HCV replication by inhibiting protein kinase R and transporting viral RNA to the site of translation and replication in the cells

    Science.gov (United States)

    Dixit, Updesh; Pandey, Ashutosh K.; Mishra, Priya; Sengupta, Amitabha; Pandey, Virendra N.

    2016-01-01

    Persistent hepatitis C virus (HCV) infection leads to chronic hepatitis C (CHC), which often progresses to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The molecular mechanisms that establish CHC and cause its subsequent development into LC and HCC are poorly understood. We have identified a cytoplasmic double-stranded RNA binding protein, Stau1, which is crucial for HCV replication. In this study, Stau1 specifically interacted with the variable-stem-loop region in the 3′ NTR and domain IIId of the HCV-IRES in the 5′ NTR, and promoted HCV replication and translation. Stau1 coimmunoprecipitates HCV NS5B and a cell factor, protein kinase R (PKR), which is critical for interferon-induced cellular antiviral and antiproliferative responses. Like Stau1, PKR displayed binding specificity to domain IIId of HCV-IRES. Stau1 binds to PKR and strongly inhibits PKR-autophosphorylation. We demonstrated that the transport of HCV RNA on the polysomes is Stau1-dependent, being mainly localized in the monosome fractions when Stau1 is downregulated and exclusively localized in the polysomes when Stau1 is overexpressed. Our findings suggest that HCV may appropriate Stau1 to its advantage to prevent PKR-mediated inhibition of eIF2α, which is required for the synthesis of HCV proteins for translocation of viral RNA genome to the polysomes for efficient translation and replication. PMID:27106056

  4. Staufen1 promotes HCV replication by inhibiting protein kinase R and transporting viral RNA to the site of translation and replication in the cells.

    Science.gov (United States)

    Dixit, Updesh; Pandey, Ashutosh K; Mishra, Priya; Sengupta, Amitabha; Pandey, Virendra N

    2016-06-20

    Persistent hepatitis C virus (HCV) infection leads to chronic hepatitis C (CHC), which often progresses to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The molecular mechanisms that establish CHC and cause its subsequent development into LC and HCC are poorly understood. We have identified a cytoplasmic double-stranded RNA binding protein, Stau1, which is crucial for HCV replication. In this study, Stau1 specifically interacted with the variable-stem-loop region in the 3' NTR and domain IIId of the HCV-IRES in the 5' NTR, and promoted HCV replication and translation. Stau1 coimmunoprecipitates HCV NS5B and a cell factor, protein kinase R (PKR), which is critical for interferon-induced cellular antiviral and antiproliferative responses. Like Stau1, PKR displayed binding specificity to domain IIId of HCV-IRES. Stau1 binds to PKR and strongly inhibits PKR-autophosphorylation. We demonstrated that the transport of HCV RNA on the polysomes is Stau1-dependent, being mainly localized in the monosome fractions when Stau1 is downregulated and exclusively localized in the polysomes when Stau1 is overexpressed. Our findings suggest that HCV may appropriate Stau1 to its advantage to prevent PKR-mediated inhibition of eIF2α, which is required for the synthesis of HCV proteins for translocation of viral RNA genome to the polysomes for efficient translation and replication. PMID:27106056

  5. Co-infecção por HIV/HCV em hospital universitário de Recife, Brasil Coinfección por HIV/HCV en hospital universitario de Recife, Brasil HIV/HCV coinfection at an university hospital in Recife, Brazil

    Directory of Open Access Journals (Sweden)

    Flávia Helena Pontes de Carvalho

    2009-02-01

    Full Text Available OBJETIVO: Estimar a prevalência do vírus da hepatite C (HCV e fatores de risco associados com a co-infecção em pessoas soropositivas para HIV. MÉTODOS: Estudo do tipo transversal, descritivo e analítico, com 343 portadores do HIV atendidos em um hospital universitário de Recife (PE, no período de março a dezembro de 2003. Os pacientes foram submetidos a um questionário padronizado sobre os fatores de risco. Nas amostras de soro foram pesquisados o anti-HCV pelo ELISA, o HCV-RNA por meio da RT-PCR e a identificação dos genótipos foi realizada no equipamento ABI377 (PE Biosystems®. As análises estatísticas utilizadas foram a univariada, a multivariada e a regressão logística múltipla. RESULTADOS: A prevalência encontrada para o HCV foi de 4,1% (14/343 pelo ELISA e de 3,2 % (11/343 quando utilizada a RT-PCR. Os genótipos mais freqüentes foram 1b (45%, 3 (33% e 1a (22%. A faixa etária com maior proporção de co-infectados foi a de 30 a 39 anos, com predomínio do sexo masculino (64,3%. Após regressão logística múltipla, apenas a variável transfusão sangüínea permaneceu como fator de risco para o HCV (OR=4,28; IC 95%: 1,44;12,73. CONCLUSÕES: A prevalência da co-infecção HIV/HCV foi baixa, a transfusão sangüínea foi um fator de risco e o genótipo 1b do HCV foi o mais freqüente.OBJETIVO: Estimar la prevalencia de virus de hepatitis C (HCV y factores de riesgo asociados con la coinfección en personas seropositivas para HIV. MÉTODOS: Estudio de tipo transversal, descriptivo y analítico, con 343 portadores de HIV atendidos en un hospital universitario de Recife (Noreste de Brasil, en el período de marzo a diciembre de 2003. Los pacientes fueron sometidos a un cuestionario estandarizado sobre los factores de riesgo. En las muestras de suero fueron pesquisados el anti-HCV por ELISA, el HCV-RNA por medio de la RT-PCR y la identificación de los genotipos fue realizada en el equipo ABI377 (PE Biosystems®. Los an

  6. HCV inter-subtype 1a/1b recombinant detected by complete-genome next-generation sequencing.

    Science.gov (United States)

    Gaspareto, Karine Vieira; Ribeiro, Roberto Marques; de Mello Malta, Fernanda; Gomes-Gouvêa, Michele Soares; Muto, Nair Hideko; Mendes-Correa, Maria Cassia; Rozanski, Andrei; Carrilho, Flair José; Sabino, Ester Cerdeira; Pinho, João Renato Rebello

    2016-08-01

    Next-generation sequencing (NGS) provides a practical approach to HCV complete-genome sequencing, detecting low-frequency variants and allowing analysis of viral genetic diversity (quasispecies) in the sample, and so far, it is very useful for identifying preexisting drug-resistant mutants and emerging escape mutations, as well as detecting viral recombinants containing genomic regions from different genotypes and subtypes. The aim of this study was to analyze the complete coding region of hepatitis C virus (HCV) genotype 1 (subtypes 1a and 1b) from patients with chronic infection who were direct-acting antiviral (DAA) naïve. Next-generation sequencing (Ion Torrent™ PGM) was used to determine the sequence of the complete coding region of 100 HCV-monoinfected DAA-naïve patients (51 and 49 subtypes 1a and 1b, respectively). We report the first description of nearly complete HCV genome sequences of subtype 1a and 1b isolates from a large population of Brazilian patients with chronic hepatitis C, and HCV-1a grouped in two different clades. Using this methodology, an inter-subtype 1a/1b recombinant was identified in this study. PMID:27194536

  7. Topological and evolutional relationships between HCV core protein and hepatic lipid vesicles: Studies in vitro and in conditionally transgenic mice

    Institute of Scientific and Technical Information of China (English)

    Ming-Ling Chang; Jeng-Chang Chen; Chau-Ting Yeh; I-Shyan Sheen; Dar-In Tai; Ming-Yu Chang; Cheng-Tang Chiu; Deng-Yn Lin; D Montgomery Bissell

    2007-01-01

    AIM: To investigate a specific association between hepatic steatosis and hepatitis C virus (HCV) core.METHODS: HeLa cells and primary mouse hepatocytes were transfected with HCV core plasmid, and conditional transgenics in which hepatic over-expression of HCV core is regulated by the tetracycline-off system, were developed. The expression of the HCV core was assessed over one to six months after withdrawal of doxycycline (dox) by immunohistochemistry (IHC)and Western blotting and by sequential liver biopsy.Hepatic steatosis was evaluated using oil red stain.8-hydroxydeoxyguanosine (8-OHdG) stains and caspase levels were conducted to clarify hepatic oxidative stress and apoptosis rate. Serum aminotransferase was checked.RESULTS: The transfected hepatocytes had globular cores under the lipid vesicles. In transgenic mice on control diet, core expression was robust, localized to the cytoplasmic vesicle membrane and strongly associated with microvesicular steatosis, which was gradually replaced by macrovesicular steatosis. However, both steatosis and core positive hepatocytes diminished with time. Increases in aminotransferase, caspase and 8-OHdG were associated with peak core expression.CONCLUSION: The core protein was readily detected and morphologically associated with steatosis in individual hepatocytes both in vitro and in vivo. In vivo,oxidative stress caused by the core potentially reduced the number of core positive hepatocytes and in parallel the level of steatosis. To our knowledge, this is the first animal model that directly shows topological relationship between HCV core and hepatic lipid vesicles.

  8. Chronic polyarthritis in a patient affected by sarcoidosis and chronic HCV infection. Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    A. Carcassi

    2011-09-01

    Full Text Available Sarcoidosis is a systemic granulomatous disease of unknown etiology that has a wide variety of clinical manifestation. Lung involvement may slowly undergo pulmonary fibrosis. Chronic sarcoid arthritis is a rare, usually non destructive arthropathy; may be a mono, oligo or polyarthritis. Knees, ankles, shoulders, wrists and small joint of the hands and feet may be involved. It can involve skin, eyes, exocrine glands such as salivary and lacrimal glands, and many other tissues. We describe the case of a 77 years old woman with a history of rhinopharyngitis with epistaxis and chronic laryngitis since youth; a dry mouth and throat, a erytematous, infiltrative skin lesion in the forehead and in the nape of the neck, a purple lesion of the left ear and nose, skin distrophy of the hands from 30 years before. She underwent an operation for a left femoral fracture with emotrasfusion 14 years ago. Then she developed a polyarthritis of the small joints of the hands (II, III and IV right DIP, I, III, e V left DIP; III and V bilateral PIP, knees, tarsi, toes and left elbow. An HCV chronic hepatitis was discovered 6 years before. She is affected by productive cough, dysphonia, dyspnea at rest, feveret, cephalea and asthenia for over 5 years. Laboratory examination revealed leukopenia, HCV hepatitis with anti HCV, HCV-RNA, transaminases elevated and cryoglobulinemia. HCV may be involved in the etiopathogenesis of rheumatic diseases, lung fibrosis and may moreover contribuite to the onset or progression of sarcoidosis; the possible pathogenesis is discussed.

  9. HCV carriers with normal aminotransferase levels: “normal” does not always mean “healthy”

    Directory of Open Access Journals (Sweden)

    Claudio Puoti

    2013-04-01

    Full Text Available BACKGROUND Approximately 30% of patients with chronic HCV infection show persistently normal ALT levels (PNALT, and another 40% have minimally raised ALT values. Although formerly referred to as “healthy” or “asymptomatic” HCV carriers, it has now become clear that the majority of these patients have some degree of histological liver damage. Controversies still exist regarding the definition of “persistent” ALT normality, the virological and histological features of these subjects, and the natural history and optimal management of chronic hepatitis C (CHC with normal ALT. Most patients with normal ALT have histologically proven liver damage that may be significant (> F2 in up to 20% of patients, and might progress toward more severe degree of liver fibrosis. A significant proportion of patients (≥ 20% experiences periods of increased serum ALT (flare associated with disease progression. AIM OF THE STUDY The introduction of the new combination therapy of PEG-IFN plus ribavirin allowed response rates higher than 50%, with a favourable risk-benefit ratio also in patients with benign or slow progressive disease. Given the efficacy of the new treatments, which soon became the standard of care for CHC, it has been suggested that the issue of whether or not to treat subjects with PNALT should be re-evaluated. ALT levels may have less importance in deciding who should be treated. Many other factors might influence the decision to treat, such as the age of the patient, HCV genotype, liver histology, patient’s motivation, symptoms, extrahepatic manifestations, comorbid illness. The role of non-invasive tools for the assessment of liver fibrosis (transient hepatic elastography remains to be further validated.

  10. Study of Erythropoeitin on IGM serum levels in HCV positive patients on regular HD

    Directory of Open Access Journals (Sweden)

    Khaled Abo Seif , Mona Hosny And Ahmed Aboud

    2012-01-01

    Full Text Available Both uremia and HD process cause immunosuppression in HD patients. There was significant increase of total serum IgG and IgM levels found in patients with chronic HCV compared with healthy controls. There is evidence pointing to direct effect of rHuEPO upon B cells. High doses of recombinant human erythropoietin (rHu EPO enhanced in vitro Ig production and proliferation of various plasma cell lines, as well as human plasma cells generated in vitro. Study was conducted at hemodialysis Unit of Shubra Municipal hospital between August 2010 to February 2011. 30 HCV positive patients on regular hemodialysis were included in study, using bicarbonate dialysate and polysulfone membrane dialyser, for 4 hours 3 times weekly. Patients were divided into 2 groups: first group: 15 patients on EPO therapy. 4000 IU/week and second group not taking EPO for all patients full clinical examination was done, CBC, BUN, serum creatinine, ALT, AST, serum albumin and serum IgM by ELISA (quantitative assay, were done. There was no significant difference between 2 groups as regards age, sex distribution, WBC count, ALT, AST, serum creatinine, BUN and IgM serum level. First group had borderline significant higher Hgb and Hct than second group (p = 0.056. Females didn't have higher serum IgM level than males (p = 0.403. All correlations of IgM serum level to other parameters of study were irrelevant. Uremia seems to protect ESRD patients on regular HD from complications of HCV and also EPO effect on Ig serum levels.

  11. In vitro assay for HCV serine proteinase expressed in insect cells

    Institute of Scientific and Technical Information of China (English)

    Li-Hua Hou; Gui-Xin Du; Rong-Bin Guan; Yi-Gang Tong; Hai-Tao Wang

    2003-01-01

    AIM: To produce the recombinant NS3 protease of hepatitis C virus with enzymatic activity in insect cells.METHODS: The gene of HCV serine proteinase domain which encodes 181 amino acids was inserted into pFastBacHTc and the recombinant plasmid pFBCNS3N was transformed into DH10Bac competent cells for transposition.After the recombinant bacmids had been determined to be correct by both blue-white colonies and PCR analysis, the isolated bacmid DNAs were transfected into Sf9 insect cells.The bacmids DNA was verified to replicate in insect cells and packaged into baculovirus particles via PCR and electronic microscopic analysis. The insect cells infected with recombinant baculovirus were determined by SDS-PAGE and Western-blot assays. The recombinant protein was soluted in N-lauryl sarcosine sodium (NLS) and purifed by metalchelated-affinity chromatography, then the antigenicity of recombinant protease was determined by enzyme-linked immunoabsorbant assay and its enzymatic activity was detected.RESULTS: The HCV NS3 protease domain was expressed in insect cells at high level and it was partially solved in NLS.Totally 0.2 mg recombinant serine proteinase domain with high purity was obtained by metal-chelated-affinity chromatography from 5×107 cells, and both antigenicity and specificity of the protein were evaluated to be high when used as antigen to detect hepatitis C patients′ sera in indirect ELISA format. In vitro cleavage assay corroborated its enzymatic activity.CONCLUSION: The recombinant HCV NS3 proteinase expressed by insect cells is a membrane-binding protein with good antigenicity and enzymatic activity.

  12. Interferon and ribavarin associated depression in hcv patients and role of selective serotonin reuptake inhibitors

    International Nuclear Information System (INIS)

    Objective: To determine the frequency and severity of depression associated with antiviral therapy of Hepatitis C Virus (HCV) infection and effect of selective serotonin reuptake Inhibitors (SSRIs) to treat these depressive symptoms. Type of Study: Observational Analytical study. Place of Study and Duration: The study was conducted at Psychiatry, Medicine and Pathology department of Combined Military Hospital Sialkot Pakistan from February 2009 to July 2010. Subjects and Methods: All the patients in this study were suffering from HCV infection and were managed with Interferon (3 m.i.u. s/c thrice weekly) and Cap Ribavirin (400 mg bid) for six months. Patients were assessed by Hospital Anxiety and Depression Scale (HADS) - Urdu Version and Beck's Depressive Inventory (BDI) Scores after twelve weeks of antiviral therapy. Depressed patients were managed with selective serotonin reuptake inhibitors (SSRIs) for six weeks and again evaluated on HADS and BDI Scores. Response to SSRIs was defined as complete response, partial response and no response. Results: A total of 105 patients were studied out of which 75 were male and 30 were female with mean age 29.4 years. Out of these 54 (51.43%) patients developed depression and this tendency to develop depression was not related with the age and sex of the patients. The mean HADS and BDI scores before and after treatments with SSRIs were compared for significance and it was quite significant. There was not a single patient who did not show response to SSRIs. Conclusion: Depression is frequently associated with antiviral therapy of HCV RNA viraemia with interferon and SSRIs have proved an effective and safe remedy in these patients. (author)

  13. Total and high molecular weight adiponectin and hepatocellular carcinoma with HCV infection.

    Directory of Open Access Journals (Sweden)

    Shuji Sumie

    Full Text Available BACKGROUND: Adiponectin is shown to be inversely associated with development and progression of various cancers. We evaluated whether adiponectin level was associated with the prevalence and histological grade of hepatocellular carcinoma (HCC, and liver fibrosis in patients with hepatitis C virus (HCV infection. METHODS: A case-control study was conducted on 97 HCC patients (cases and 97 patients (controls matched for sex, Child-Pugh grade and platelet count in patients with HCV infection. The serum total and high molecular weight (HMW adiponectin levels were measured by enzyme-linked immunosorbent assays and examined in their association with the prevalence of HCC. In addition, the relationship between these adiponectin levels and body mass index (BMI, progression of liver fibrosis, and histological grade of HCC was also evaluated. Liver fibrosis was assessed using the aspartate aminotransferase to platelet ratio index (APRI. RESULTS: There were no significant differences in the serum total and HMW adiponectin levels between cases and controls. Moreover, there were no inverse associations between serum total and HMW adiponectin levels and BMI in both cases and controls. On the other hand, serum total and HMW adiponectin levels are positively correlated with APRI in both cases (r = 0.491, P<0.001 and r = 0.485, P<0.001, respectively and controls (r = 0.482, P<0.001 and r = 0.476, P<0.001, respectively. Interestingly, lower serum total (OR 11.76, 95% CI: 2.97-46.66 [P<0.001] and HMW (OR 10.24, CI: 2.80-37.40 [P<0.001] adiponectin levels were independent risk factors of worse histological grade of HCC. CONCLUSIONS: Our results suggested that serum total and HMW adiponectin levels were predictors of liver fibrosis, but not prevalence of HCC in patients with HCV infection. Moreover, low these adiponectin levels were significantly associated with worse histological grades.

  14. Mosaic gene network modelling identified new regulatory mechanisms in HCV infection.

    Science.gov (United States)

    Popik, Olga V; Petrovskiy, Evgeny D; Mishchenko, Elena L; Lavrik, Inna N; Ivanisenko, Vladimir A

    2016-06-15

    Modelling of gene networks is widely used in systems biology to study the functioning of complex biological systems. Most of the existing mathematical modelling techniques are useful for analysis of well-studied biological processes, for which information on rates of reactions is available. However, complex biological processes such as those determining the phenotypic traits of organisms or pathological disease processes, including pathogen-host interactions, involve complicated cross-talk between interacting networks. Furthermore, the intrinsic details of the interactions between these networks are often missing. In this study, we developed an approach, which we call mosaic network modelling, that allows the combination of independent mathematical models of gene regulatory networks and, thereby, description of complex biological systems. The advantage of this approach is that it allows us to generate the integrated model despite the fact that information on molecular interactions between parts of the model (so-called mosaic fragments) might be missing. To generate a mosaic mathematical model, we used control theory and mathematical models, written in the form of a system of ordinary differential equations (ODEs). In the present study, we investigated the efficiency of this method in modelling the dynamics of more than 10,000 simulated mosaic regulatory networks consisting of two pieces. Analysis revealed that this approach was highly efficient, as the mean deviation of the dynamics of mosaic network elements from the behaviour of the initial parts of the model was less than 10%. It turned out that for construction of the control functional, data on perturbation of one or two vertices of the mosaic piece are sufficient. Further, we used the developed method to construct a mosaic gene regulatory network including hepatitis C virus (HCV) as the first piece and the tumour necrosis factor (TNF)-induced apoptosis and NF-κB induction pathways as the second piece. Thus

  15. New pandemics: HIV and AIDS, HCV and chronic hepatitis, Influenza virus and flu

    OpenAIRE

    Cohen Éric A; Wainberg Mark A; Dubuisson Jean; Gatignol Anne; Darlix Jean-Luc

    2007-01-01

    Abstract New pandemics are a serious threat to the health of the entire world. They are essentially of viral origin and spread at large speed. A meeting on this topic was held in Lyon, France, within the XIXth Jacques Cartier Symposia, a series of France-Québec meetings held every year. New findings on HIV and AIDS, on HCV and chronic hepatitis, and an update on influenza virus and flu were covered during this meeting on December 4 and 5, 2006. Aspects of viral structure, virus-host interacti...

  16. Is autoimmune hepatitis a frequent finding among HCV patients with intense interface hepatitis?

    Institute of Scientific and Technical Information of China (English)

    Rosilene; G; Badiani; Vitória; Becker; Renata; M; Perez; Carla; AL; Matos; Lara; B; Lemos; Valéria; P; Lanzoni; Luis; Eduardo; C; Andrade; Alessandra; Dellavance; Antonio; Eduardo; B; Silva; Maria; Lucia; G; Ferraz

    2010-01-01

    AIM:To evaluate the overlap of autoimmune hepatitis in hepatitis C virus(HCV)-infected patients with intense interface hepatitis.METHODS:Among 1759 patients with hepatitis C submitted to liver biopsy,92(5.2%) presented intense interface hepatitis.These patients were evaluated regarding the presence of antinuclear antibody(ANA),anti-smooth muscle antibody(SMA) and anti-liver/kidney microsomal antibody(LKM-1),levels of γ-globulin and histological findings related to autoimmune hepatitis(plasma cell infiltrate...

  17. Female sex and IL28B, a synergism for spontaneous viral clearance in hepatitis C virus (HCV seroconverters from a community-based cohort.

    Directory of Open Access Journals (Sweden)

    Charlotte H B S van den Berg

    Full Text Available BACKGROUND & AIMS: Since acute hepatitis C virus (HCV infection is often asymptomatic, it is difficult to examine the rate and determinants of spontaneous clearance. Consequently, these studies are subject to bias, which can potentially lead to biased rates of viral clearance and risk estimates. We evaluated determinants of spontaneous HCV clearance among HCV seroconverters identified in a unique community-based cohort. METHODS: Subjects were 106 drug users with documented dates of HCV seroconversion from the Amsterdam Cohort Study. Logistic regression was used to examine sociodemographic, behavioral, clinical, viral and host determinants, measured around acute infection, of HCV clearance. RESULTS: The spontaneous viral clearance rate was 33.0% (95% confidence interval (CI 24.2-42.8. In univariate analyses female sex and fever were significantly associated with spontaneous clearance. The favorable genotypes for rs12979860 (CC and rs8099917 (TT were associated with spontaneous clearance, although borderline significant. In multivariate analysis, females with the favorable genotype for rs12979860 (CC had an increased odds to spontaneously clear HCV infection (adjusted OR 6.62, 95% 2.69-26.13, whereas females with the unfavorable genotype were as likely as men with the favorable and unfavorable genotype to clear HCV. Chronic Hepatitis B infection and absence of HIV coinfection around HCV seroconversion also favor HCV clearance. CONCLUSIONS: This study shows that co-infection with HIV and HBV and genetic variation in the IL28B region play an important role in spontaneous clearance of HCV. Our findings suggest a possible synergistic interaction between female sex and IL28B in spontaneous clearance of HCV.

  18. Construction and characterization of an HCV-derived multi-epitope peptide antigen containing B-cell HVR1 mimotopes and T-cell conserved epitopes

    Institute of Scientific and Technical Information of China (English)

    GAO; Jun; GONG; Yuping; ZHAO; Ping; ZHU; Qing; YANG; Xiaoping; QI; Zhongtian

    2006-01-01

    Hepatitis C (HCV) genome is highly variable, particularly in the hypervariable region 1(HVR1) of its E2 envelope gene. The variability of HCV genome has been a major obstacle for developing HCV vaccines. Due to B-cell HVR1 mimotopes mimicking the antigenicity of natural HVR1 epitopes and some T-cell epitopes from the consensus sequence of HCV genes conserving among the different HCV genotypes, we synthesized an minigene of HCV-derived multi-epitope peptide antigen (CMEP), which contains 9 B-cell HVR1 mimotopes in E2, 2 conserved CTL epitopes in C, 1conserved CTL epitope in NS3 and 1 conserved Th epitope in NS3. This minigene was cloned into a GST expression vector to generate a fusion protein GST-CMER The immunogenic properties of CEMP were characterized by HCV infected patients' sera, and found that the reactivity frequency reached 75%. The cross reactivity of anti-CEMP antibody with different natural HVR1 variants was up to 90%. Meanwhile, we constructed an HCV DNA vaccine candidate, plasmid pVAX1.0-st-CMEP carrying the recombinant gene (st) of a secretion signal peptide and PADRE universal Th cell epitope sequence in front of the CMEP minigene. Immunization of rabbits with pVAX1.0-st-CMEP resulted in the production of antibody, which was of the same cross reactivity as the fusion protein GST-CMEP.Our findings indicate that the HCV-derived multi-epitope peptide antigen in some degree possessed the characteristics of neutralizing HCV epitopes, and would be of the value as a candidate for the development of HCV vaccines.

  19. Test

    DEFF Research Database (Denmark)

    Bendixen, Carsten

    2014-01-01

    Bidrag med en kortfattet, introducerende, perspektiverende og begrebsafklarende fremstilling af begrebet test i det pædagogiske univers.......Bidrag med en kortfattet, introducerende, perspektiverende og begrebsafklarende fremstilling af begrebet test i det pædagogiske univers....

  20. PCR-Based Molecular Diagnosis of Hepatitis Virus (HBV and HDV) in HCV Infected Patients and Their Biochemical Study

    Science.gov (United States)

    Anwar, Muhammad Ayaz; Raheel, Ummar; Badshah, Yasmeen; Akhtar, Hashaam; Tamanna, Kosar; Tahir, Muhammad; Sadaf Zaidi, Najam us Sahar

    2016-01-01

    Seroprevalence of HCV indicates that HCV is found in more than 10% of HBV- or HDV-infected patients worldwide leading to liver disease. Here we show HBV and HDV coinfection association with HCV infected Pakistani patients, study of disease severity, and possible interpretation of associated risk factors in coinfected patients. A total of 730 liver diseased patients were included, out of which 501 were found positive for HCV infection via PCR. 5.1% of patients were coinfected with HBV while 1% were coinfected with HBV and HDV both. LFTs were significantly altered in dually and triply infected patients as compared to single HCV infection. Mean bilirubin, AST, and ALT levels were highest (3.25 mg/dL, 174 IU/L, and 348 IU/L) in patients with triple infection while dual infection LFTs (1.6 mg/dL, 61 IU/L, and 74 IU/L) were not high as in single infection (1.9 mg/dL, 76 IU/L, and 91 IU/L). The most prominent risk factor in case of single (22%) and dual infection (27%) group was “reuse of syringes” while in triple infection it was “intravenous drug users” (60%). It is concluded that HBV and HDV coinfections are strongly associated with HCV infected Pakistani patients and in case of severe liver disease the possibility of double and triple coinfection should be kept in consideration. PMID:27366331

  1. The HCV non-nucleoside inhibitor Tegobuvir utilizes a novel mechanism of action to inhibit NS5B polymerase function.

    Directory of Open Access Journals (Sweden)

    Christy M Hebner

    Full Text Available Tegobuvir (TGV is a novel non-nucleoside inhibitor (NNI of HCV RNA replication with demonstrated antiviral activity in patients with genotype 1 chronic HCV infection. The mechanism of action of TGV has not been clearly defined despite the identification of resistance mutations mapping to the NS5B polymerase region. TGV does not inhibit NS5B enzymatic activity in biochemical assays in vitro, suggesting a more complex antiviral mechanism with cellular components. Here, we demonstrate that TGV exerts anti-HCV activity utilizing a unique chemical activation and subsequent direct interaction with the NS5B protein. Treatment of HCV subgenomic replicon cells with TGV results in a modified form of NS5B with a distinctly altered mobility on a SDS-PAGE gel. Further analysis reveals that the aberrantly migrating NS5B species contains the inhibitor molecule. Formation of this complex does not require the presence of any other HCV proteins. The intensity of the aberrantly migrating NS5B species is strongly dependent on cellular glutathione levels as well as CYP 1A activity. Furthermore analysis of NS5B protein purified from a heterologous expression system treated with TGV by mass spectrometry suggests that TGV undergoes a CYP- mediated intracellular activation step and the resulting metabolite, after forming a glutathione conjugate, directly and specifically interacts with NS5B. Taken together, these data demonstrate that upon metabolic activation TGV is a specific, covalent inhibitor of the HCV NS5B polymerase and is mechanistically distinct from other classes of the non-nucleoside inhibitors (NNI of the viral polymerase.

  2. The HCV non-nucleoside inhibitor Tegobuvir utilizes a novel mechanism of action to inhibit NS5B polymerase function.

    Science.gov (United States)

    Hebner, Christy M; Han, Bin; Brendza, Katherine M; Nash, Michelle; Sulfab, Maisoun; Tian, Yang; Hung, Magdeleine; Fung, Wanchi; Vivian, Randall W; Trenkle, James; Taylor, James; Bjornson, Kyla; Bondy, Steven; Liu, Xiaohong; Link, John; Neyts, Johan; Sakowicz, Roman; Zhong, Weidong; Tang, Hengli; Schmitz, Uli

    2012-01-01

    Tegobuvir (TGV) is a novel non-nucleoside inhibitor (NNI) of HCV RNA replication with demonstrated antiviral activity in patients with genotype 1 chronic HCV infection. The mechanism of action of TGV has not been clearly defined despite the identification of resistance mutations mapping to the NS5B polymerase region. TGV does not inhibit NS5B enzymatic activity in biochemical assays in vitro, suggesting a more complex antiviral mechanism with cellular components. Here, we demonstrate that TGV exerts anti-HCV activity utilizing a unique chemical activation and subsequent direct interaction with the NS5B protein. Treatment of HCV subgenomic replicon cells with TGV results in a modified form of NS5B with a distinctly altered mobility on a SDS-PAGE gel. Further analysis reveals that the aberrantly migrating NS5B species contains the inhibitor molecule. Formation of this complex does not require the presence of any other HCV proteins. The intensity of the aberrantly migrating NS5B species is strongly dependent on cellular glutathione levels as well as CYP 1A activity. Furthermore analysis of NS5B protein purified from a heterologous expression system treated with TGV by mass spectrometry suggests that TGV undergoes a CYP- mediated intracellular activation step and the resulting metabolite, after forming a glutathione conjugate, directly and specifically interacts with NS5B. Taken together, these data demonstrate that upon metabolic activation TGV is a specific, covalent inhibitor of the HCV NS5B polymerase and is mechanistically distinct from other classes of the non-nucleoside inhibitors (NNI) of the viral polymerase. PMID:22720059

  3. Recent advances in managing chronic HCV infection: focus on therapy in patients with severe liver disease.

    Science.gov (United States)

    Maan, Raoel; van der Meer, Adriaan J

    2016-01-01

    Chronic hepatitis C virus (HCV) infection still represents a major public health problem, as it is thought to be responsible for more than 350,000 deaths around the globe on a yearly basis. Fortunately, successful eradication of the virus has been associated with improved clinical outcome and reduced mortality rates. In the past few years, treatment has improved considerably by the implementation of direct-acting antivirals (DAAs). From 2014 onwards, sofosbuvir, simeprevir, daclatasvir, ledipasvir, paritaprevir, ombitasvir, and dasabuvir have been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Regimens with various combinations of these new drugs, without the use of interferon (IFN), proved to be very effective and well tolerated, even among patients with advanced liver disease. Moreover, treatment duration could be shortened to 12 weeks in the majority of patients. The high costs of these DAAs, however, limit the availability of IFN-free therapy worldwide. Even in wealthy countries, it is deemed necessary to prioritize DAA treatment in order to limit the immediate impact on the health budget. As patients with advanced liver disease are in most need of HCV clearance, many countries decided to treat those patients first. In the current review, we focus on the currently available IFN-free treatment options for patients with cirrhosis. We discuss the virological efficacy as well as the clinical relevance of these regimens among this specific patient population. PMID:27006761

  4. Methodologies for the analysis of HCV-specific CD4+ T cells

    Directory of Open Access Journals (Sweden)

    Megha eLokhande

    2015-02-01

    Full Text Available Virus-specific CD4+ T cells play a major role in viral infections, such as hepatitis C virus (HCV. Viral clearance is associated with vigorous and multispecific CD4+ T cell responses, while chronic infection has been shown to be associated with weak or absent T cell responses. Most of these studies have used functional assays to analyse virus-specific CD4+ T cell responses; however, these and other detection methods have various limitations. Therefore, the important question of whether virus-specific CD4+ T cells are completely absent or primarily impaired in specific effector functions during chronic infection, has yet to be analysed in detail. A novel assay, in which virus-specific CD4+ T cell frequencies can be determined by de novo CD154 (CD40 ligand expression in response to viral antigens, can help to overcome some of the limitations of functional assays and restrictions of multimer-based methods. This and other current established methods for the detection of HCV-specific CD4+ T cells will be discussed in this review.

  5. Treatment of Patients With HCV Related Cirrhosis: Many Rewards With Very Few Risks

    Directory of Open Access Journals (Sweden)

    Alessio Aghemo

    2012-06-01

    Full Text Available Antiviral treatment of chronic hepatitis C virus (HCV is aimed at the persistent eradication of the virus, the so-called sustained virological response (SVR, with the aim ultimately being to prevent the development of liver-related complications and improve patients’ survival. Patients with HCV-related compensated cirrhosis are the group most likely to benefit from viral clearance, as several retrospective studies have shown liver complications rates to be positively modified by the achievement of a SVR. Whether these benefits rely on viral clearance or on the histological improvements seen following successful interferon (IFn-based therapies has recently been a matter for debate, as studies have shown cirrhosis to regress in some patients with a SVR. Whatever the mechanisms, cirrhosis has the uncanny ability to be both a dominant indication for therapy, as well as one of the strongest baseline factors associated with reduced efficacy of any IFn-based regimen. This has led to the development of alternative treatment strategies, such as low dose pegylated IFn (PegIFn monotherapy, that unfortunately has proven to be of limited efficacy. For this reason regimens able to clear the virus without relying on the broad antiviral effect of IFN are eagerly awaited.

  6. Losartan may inhibit the progression of liver fibrosis in chronic HCV patients

    Science.gov (United States)

    Salama, Zakaria A.; Sadek, Ahmed; Abdelhady, Ahmed M.; Morsy, Shereif Ahmed; Esmat, Gamal

    2016-01-01

    Background Abundant experimental evidence indicates overproduction of angiotensin II in the injured liver, and a role in stimulation of hepatic stellate cell (HSC) activation and fibrogenesis thereby, representing an attractive antifibrotic target. The aim of this study was to examine the antifibrotic effect of losartan on histopathologic level in chronic HCV patients. Methods A prospective study on fifty patients with chronic HCV and liver fibrosis proved by liver biopsy was conducted. They included patients who did not respond (n=36) or comply (n=2) or receive therapy due to established cirrhosis (n=10), or refused to receive (n=2) combined interferon and ribavirin therapy. They were divided randomly into 2 groups. The 1st group (n=25) was given losartan 50 mg OD for 1 year and the 2nd group (25 patients) was given silymarin, 140 mg t.i.d., (silymarin group). Liver biopsy was done at baseline and 1 year from the onset of treatment (end of study). Results In the second liver biopsy after 1 year, the decrease in fibrosis stage was significantly different between losartan group and silymarin group (a decrease of 1.88±0.96 (50.9%) vs. 0.45±0.93 (11.7%), respectively; Pfibrosis stage was observed in 14/16 patients vs. 2/11 in silymarin group (Pfibrosis stage but had no effect on the grade of inflammation.

  7. Effect of ethanol on innate antiviral pathways and HCV replication in human liver cells

    Directory of Open Access Journals (Sweden)

    Fausto Nelson

    2005-12-01

    Full Text Available Abstract Alcohol abuse reduces response rates to IFN therapy in patients with chronic hepatitis C. To model the molecular mechanisms behind this phenotype, we characterized the effects of ethanol on Jak-Stat and MAPK pathways in Huh7 human hepatoma cells, in HCV replicon cell lines, and in primary human hepatocytes. High physiological concentrations of acute ethanol activated the Jak-Stat and p38 MAPK pathways and inhibited HCV replication in several independent replicon cell lines. Moreover, acute ethanol induced Stat1 serine phosphorylation, which was partially mediated by the p38 MAPK pathway. In contrast, when combined with exogenously applied IFN-α, ethanol inhibited the antiviral actions of IFN against HCV replication, involving inhibition of IFN-induced Stat1 tyrosine phosphorylation. These effects of alcohol occurred independently of i alcohol metabolism via ADH and CYP2E1, and ii cytotoxic or cytostatic effects of ethanol. In this model system, ethanol directly perturbs the Jak-Stat pathway, and HCV replication. Infection with Hepatitis C virus is a significant cause of morbidity and mortality throughout the world. With a propensity to progress to chronic infection, approximately 70% of patients with chronic viremia develop histological evidence of chronic liver diseases including chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The situation is even more dire for patients who abuse ethanol, where the risk of developing end stage liver disease is significantly higher as compared to HCV patients who do not drink 12. Recombinant interferon alpha (IFN-α therapy produces sustained responses (ie clearance of viremia in 8–12% of patients with chronic hepatitis C 3. Significant improvements in response rates can be achieved with IFN plus ribavirin combination 456 and pegylated IFN plus ribavirin 78 therapies. However, over 50% of chronically infected patients still do not clear viremia. Moreover, HCV-infected patients who abuse

  8. G-CSF in Peg-IFN induced neutropenia in liver transplanted patients with HCV recurrence

    Institute of Scientific and Technical Information of China (English)

    Francesca Lodato; Francesco Azzaroli; Maria Rosa Tamè; Maria Di Girolamo; Federica Buonfiglioli; Natalia Mazzella; Paolo Cecinato; Enrico Roda; Giuseppe Mazzella

    2009-01-01

    AIM: To evaluate the efficacy of granulocyte colony stimulating factors (G-CSF) in liver transplanted patients with hepatitis C (HCV) recurrence and Pegylated-IFN α-2b induced neutropenia, and to evaluate the impact of G-CSF administration on virological response.METHODS: Sixty-eight patients undergoing antiviral treatment for post-liver transplantation (OLT) HCV recurrence were enrolled.All patients developing neutropenia received G-CSF.RESULTS: Twenty three (34%) received G-CSF.Mean neutrophil count at the onset of neutropenia was 700/mmc (range 400-750/mmc); after 1 mo of G-CSF it increased to 1210/mmc (range 300-5590/mmc) ( P < 0.0001).Three patients did not respond to G-CSF.Treatment duration was similar in neutropenic and non-neutropenic patients.No differences in the rate of discontinuation, infections or virological response were observed between the two groups.G-CSF was protective for the onset of de novo autoimmune hepatitis ( P < 0.003).CONCLUSION: G-CSF administration is effective in the case of Peg-IFN induced neutropenia increasing neutrophil count, prolonging treatment and leading to sustained virological response (SVR) rates comparable to non-neutropenic patients.It prevents the occurrence of de novo autoimmune hepatitis.

  9. Immune signatures in human PBMCs of idiotypic vaccine for HCV-related lymphoproliferative disorders

    Directory of Open Access Journals (Sweden)

    Romagnoli Luca

    2010-02-01

    Full Text Available Abstract Hepatitis C virus (HCV is one of the major risk factors for chronic hepatitis, which may progress to cirrhosis and hepatocellular carcinoma, as well as for type II mixed cryoglobulinemia (MC, which may further evolve into an overt B-cell non-Hodgkin's lymphoma (NHL. It has been previously shown that B-cell receptor (BCR repertoire, expressed by clonal B-cells involved in type II MC as well as in HCV-associated NHL, is constrained to a limited number of variable heavy (VH- and light (VL-chain genes. Among these, the VK3-20 light chain idiotype has been selected as a possible target for passive as well as active immunization strategy. In the present study, we describe the results of a multiparametric analysis of the innate and early adaptive immune response after ex vivo stimulation of human immune cells with the VK3-20 protein. This objective has been pursued by implementing high-throughput technologies such as multiparameter flow cytometry and multiplex analysis of cytokines and chemokines.

  10. Genetic Markers of the Host in Persons Living with HTLV-1, HIV and HCV Infections

    Directory of Open Access Journals (Sweden)

    Tatiane Assone

    2016-02-01

    Full Text Available Human T-cell leukemia virus type 1 (HTLV-1, hepatitis C virus (HCV and human immunodeficiency virus type 1 (HIV-1 are prevalent worldwide, and share similar means of transmission. These infections may influence each other in evolution and outcome, including cancer or immunodeficiency. Many studies have reported the influence of genetic markers on the host immune response against different persistent viral infections, such as HTLV-1 infection, pointing to the importance of the individual genetic background on their outcomes. However, despite recent advances on the knowledge of the pathogenesis of HTLV-1 infection, gaps in the understanding of the role of the individual genetic background on the progress to disease clinically manifested still remain. In this scenario, much less is known regarding the influence of genetic factors in the context of dual or triple infections or their influence on the underlying mechanisms that lead to outcomes that differ from those observed in monoinfection. This review describes the main factors involved in the virus–host balance, especially for some particular human leukocyte antigen (HLA haplotypes, and other important genetic markers in the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP and other persistent viruses, such as HIV and HCV.

  11. MicroRNAs, HIV and HCV: a complex relation towards pathology.

    Science.gov (United States)

    Piedade, Diogo; Azevedo-Pereira, José Miguel

    2016-05-01

    MicroRNAs are small non-coding RNAs that modulate protein production by post-transcriptional gene regulation. They impose gene expression control by interfering with mRNA translation and stability in cell cytoplasm through a mechanism involving specific binding to mRNA based on base pair complementarity. Because of their intracellular replication cycle it is no surprise that viruses evolved in a way that allows them to use microRNAs to infect, replicate and persist in host cells. Several ways of interference between virus and host-cell microRNA machinery have been described. Most of the time, viruses drastically alter host-cell microRNA expression or synthesize their own microRNA to facilitate infection and pathogenesis. HIV and HCV are two prominent examples of this complex interplay revealing how fine-tuning of microRNA expression is crucial for controlling key host pathways that allow viral infection and replication, immune escape and persistence. In this review we delve into the mechanisms underlying cellular and viral-encoded microRNA functions in the context of HIV and HCV infections. We focus on which microRNAs are differently expressed and deregulated upon viral infection and how these alterations dictate the fate of virus and cell. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27059433

  12. Immune Exhaustion and Immune Senescence – Two Distinct Pathways for HBV Vaccine Failure during HCV and/or HIV Infection

    OpenAIRE

    Yao, Zhi Q.; Moorman, Jonathan P.

    2013-01-01

    Given the shared risk factors for transmission, co-infection of hepatitis B virus (HBV) with hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV) is quite common, and may lead to increases in morbidity and mortality. As such, HBV vaccine is recommended as the primary means to prevent HBV super-infection in HCV- and/or HIV-infected individuals. However, vaccine response (sero-conversion with a hepatitis B surface antibody titer >10 IU/L) in this setting is often blunted, with poor...

  13. Construction and Immunological Evaluation of Multivalent Hepatitis B Virus (HBV) Core Virus-Like Particles Carrying HBV and HCV Epitopes▿

    OpenAIRE

    Sominskaya, Irina; Skrastina, Dace; Dislers, Andris; Vasiljev, Denis; Mihailova, Marija; Ose, Velta; Dreilina, Dzidra; Pumpens, Paul

    2010-01-01

    A multivalent vaccine candidate against hepatitis B virus (HBV) and hepatitis C virus (HCV) infections was constructed on the basis of HBV core (HBc) virus-like particles (VLPs) as carriers. Chimeric VLPs that carried a virus-neutralizing HBV pre-S1 epitope corresponding to amino acids (aa) 20 to 47 in the major immunodominant region (MIR) and a highly conserved N-terminal HCV core epitope corresponding to aa 1 to 60 at the C terminus of the truncated HBcΔ protein (N-terminal aa 1 to 144 of f...

  14. IFN-αα induced psoriatic arthritis and HCV-related liver cirrhosis. Therapeutic options and patient’s opinion

    Directory of Open Access Journals (Sweden)

    M. Piga

    2011-09-01

    Full Text Available Hepatitis C virus (HCV infection in the setting of Psoriatic Arthritis is an additional variable to be considered in the therapeutic approach to the disease because of the complications of an immunosuppressive treatment in the course of a chronic infection and the possible hepatotoxicity of many drugs conventionally used to treat psoriatic arthritis. The case reported explores the therapeutic options in a patient with IFN-α induced psoriatic arthritis, characterised by severe arthritis and psoriasis but also the concomitant presence of HCV chronic hepatitis, in light of the patient’s concerns

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

    OpenAIRE

    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. Seq...

  16. Potential of G-CSF supplementation to counter the neutrophil effects of standard PEG-IFNα plus ribavirin combination therapy for treating HCV-related cirrhosis

    Institute of Scientific and Technical Information of China (English)

    孙素梅

    2013-01-01

    Objective To investigate the effects of the granulocyte colony stimulating factor (G-CSF) with pegylated interferon alpha (PEC-IFNα) plus ribavirin (RBV) and PEG-IFNαreduction in the treatment of the compensatory hepatitis C virus (HCV) -related cirrhosis.Methods Fourty-eight patients with compensatory HCV-related

  17. HBV or HCV coinfections and risk of myocardial infarction in HIV-infected individuals: the D:A:D Cohort Study

    DEFF Research Database (Denmark)

    Weber, Rainer; Sabin, Caroline; Reiss, Peter; de Wit, Stephane; Worm, Signe W; Law, Matthew; Dabis, Francois; D'Arminio Monforte, Antonella; Fontas, Eric; El-Sadr, Wafaa; Kirk, Ole; Rickenbach, Martin; Phillips, Andrew; Ledergerber, Bruno; Lundgren, Jens

    2010-01-01

    Data on a link between HCV or HBV infection and the development of cardiovascular disease among HIV-negative and HIV-positive individuals are conflicting. We sought to investigate the association between HBV or HCV infection and myocardial infarction in HIV-infected individuals....

  18. Induction of intrahepatic HCV NS4B, NS5A and NS5B-specific cellular immune responses following peripheral immunization.

    Directory of Open Access Journals (Sweden)

    Krystle A Lang Kuhs

    Full Text Available Numerous studies have suggested that an effective Hepatitis C Virus (HCV vaccine must induce strong cytotoxic and IFN-γ+ T cell responses targeting the non-structural region of the virus. Most importantly, these responses must be able to migrate into and remain functional within the liver, an organ known to cause T cell tolerance. Using three novel HCV DNA vaccines encoding non-structural proteins NS4B, NS5A and NS5B, we assessed the ability of peripheral immunization to induce functional intrahepatic immunity both in the presence and absence of cognate HCV antigen expression within the liver. We have shown that these constructs induced potent HCV-specific CD4+ and CD8+ T cell responses in the spleen of C57BL/6 mice and that these responses were detected within the liver following peripheral immunization. Additionally, using a transfection method to express HCV antigen within the liver, we showed that intrahepatic HCV-specific T cells remained highly functional within the liver and retained the ability to become highly activated as evidenced by upregulation of IFN-γ and clearance of HCV protein expressing hepatocytes. Taken together, these findings suggest that peripheral immunization can induce potent HCV-specific T cell responses able to traffic to and function within the tolerant environment of the liver.

  19. 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; Jensen, Tanja B; Bukh, Jens

    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 of...

  20. 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; Hellstrand, Kristoffer; Alaeus, Annette; Lagging, Martin

    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 pa......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......-10 <150 pg/ml is predictive of a favourable viral response to HCV therapy in HIV-HCV co-infected patients, and may thus be useful in encouraging such difficult-to-treat patients to initiate therapy....

  1. Surveillance of risk behawiors facilitating among commercial sex works and analysis of HIV, Syphilis, HCV and HBV infection%街头暗娼危险行为监测和HIV HCV HbsAg梅毒检测结果分析

    Institute of Scientific and Technical Information of China (English)

    姜楠

    2012-01-01

    目的 分析本市女性性服务人群艾滋病病毒(HIV)、梅毒螺旋体(TP)、丙型肝炎病毒(HCV)、乙型肝炎病毒(HBV)感染情况.为我市疾病预防和控制提供依据.方法 对性服务者填写调查问卷、采集血液标本,用酶联免疫吸附试验(ELISA)、蛋白印迹试验(WB)检测、确证HIV感染;用快速血浆凝集试验(RPR)明胶颗粒凝集试验( TPPA)检测梅毒感染;用ELISA检测丙肝和乙肝.结果 最近一次与客人使用安全套的占55.69,与客人每次都用安全套的占12.66%.475例性服务人员中检出HIV抗体阳性1例(0.21%),梅毒阳性4例(0.84%),HbsAg阳性38例(11.95%),HCV阳性26例(5.42%).结论 应加大对该类人群的宣传和干预力度,充分利用各种机构促进SSWs人群的健康,从而遏制AIDS/STDR流行.%Objective To understand HIV Syphilis HCV and HBV infection among sex service crowd and to provide information for controlling these diseases. Methods Sex workers filled out questionnaires, blood collected specimens, enzyme immunosorbent adsorption test (ELISA) , protein imprinting test (WB) detection, corroborating HIV infection; With the fast plasma agglutinate experiment (RPR) gelatin particles agglutinate experiment (TPPA) testing syphilis infection ; With ELISA test hepatitis c and hepatitis b, in strict accordance with the operation of the kit. Results Guest 3. 56m Recent and guest condoms 55. 69, with the guest of every time use condoms accounted for 12. 66% . Example, sex service personnel in the check out anti -HIV positive in 1 case (accuracy is 0.21%) syphilis positive 4 cases (0. 84% ) HbsAg positive (38 cases 11. 95% ) HCV positive 26 cases (statistics show 5. 42% ). Conclusions We should strengthen the efficiency of this spread of people's health educations our chance.

  2. Hepatitis C risk assessment,testing and referral for treatment in urban primary care:Role of race and ethnicity

    Institute of Scientific and Technical Information of China (English)

    Stacey B Trooskin; Victor J Navarro; Robert J Winn; David J Axelrod; A Scott McNeal; Maricruz Velez; Steven K Herrine; Simona Rossi

    2007-01-01

    AIM:To determine rates of hepatitis C(HCV)risk factor ascertainment,testing,and referral in urban primary care practices,with particular attention to the effect of race and ethnicity.METHODS:Retrospective chart review from four primary care sites in Philadelphia;two academic primary care practices and two community clinics was performed.Demographics,HCV risk factors,and other risk exposure information were collected.RESULTS:Four thousand four hundred and seven charts were reviewed.Providers documented histories of injection drug use(IDU)and transfusion for less than 20% and 5% of patients,respectively.Only 55% of patients who admitted IDU were tested for HCV.Overall,minorities were more likely to have information regarding a risk factor documented than their white counterparts (79% vs 68%,P < 0.0001).Hispanics were less likely to have a risk factor history documented,compared to blacks and whites(P < 0.0001).Overall,minorities were less likely to be tested for HCV than whites in the presence of a known risk factor(23% vs 35%,P = 0.004).Among patients without documentation of risk factors,blacks and Hispanics were more likely to be tested than whites(20% and 24%,vs 13%,P < 0.005,respectively).CONCLUSION:(1)Documentation of an HCV risk factor history in urban primary care is uncommon,(2)Racial differences exist with respect to HCV risk factor ascertainment and testing,(3)Minority patients,positive for HCV,are less likely to be referred for subspecialty care and treatment.Overall,minorities are less likely to be tested for HCV than whites in the presence of a known risk factor.

  3. Bioinformatics e Biostatistics applied to research in pediatric genetic disease. Clinical evidence in IFNλ4 polymorphisms associated with HCV infection in patients with beta thalassemia and WGCNA analysis weighted for IFNλ4 genotype rs12979860 to detect RPL9P18 as hub in HCV infected cell.

    OpenAIRE

    Marceddu, Giuseppe

    2015-01-01

    Genome-wide association studies have identified host genetic variation to be critical for spontaneous clearance and treatment response in patients infected with hepatitis C virus (HCV). We demonstrated the same in patients with thalassemia major infected by genotype 1b of HCV. In the present first part study we retrospectively analyzed 368 anti-HCV positive patients with beta-thalassemia in two Italian major thalassemic centers (Cagliari and Turin). The strongest IFNλ4 SN...

  4. Adherence with screening guidelines for hepatitis C testing among HIV-infected patients

    Directory of Open Access Journals (Sweden)

    S Jonckheere

    2012-11-01

    Full Text Available Purpose of the study: Co-infection with HIV / hepatitis C virus (HCV occurs commonly due to similar routes of transmission, mainly in MSM and IVDU patients. In 2009, EACS guidelines introduced the notion of systematic annual HCV screening among HIV-infected patients. This study evaluated staff knowledge, adherence to HCV screening recommendations and seroconversion rates for HCV in our HIV Reference Centre. Methods: Eight physicians (HIV specialists were interviewed on recommendations and perceived adherence to EACS clinical guidelines on HCV screening [1]. We then reviewed medical records of our cohort of HIV-infected patients on regular follow-up in our centre each year, from 2008 to 2011. We considered a patient to be on regular follow-up when records showed at least two clinical reviews and one HIV viral load testing during the year. Demographic features and HCV serology tests were collected from the operating software of our institution (Medical Explorer v3r9, 2008. Diagnosis of HCV was retained when serology became positive and HCV RNA was detected. Summary of results: Though knowledge of current guidelines was excellent (100%, staff claimed a 87.5% adherence rate to these recommendations. Rate of screening rose gradually between 2008 and 2011, especially after introduction of EACS guidelines in 2009 (Table 1 and Fig. 1. The maximal screening rate was in 2011, with 44% of patients tested among the general HIV population and 57% among MSM bisexual patients. This trend was statistically significant in both populations (p<0.01. The year 2011 displayed a marked increase in diagnosis of HCV infection, with 8 new patients diagnosed in a 963-patient-large cohort (all were MSM. Conclusion: In our centre, knowledge of EACS guidelines on screening for HCV was good but adherence to these recommendations is poor, though it improves over time. It is consistent with published rates of compliance to clinical guidelines on screening policies for HCV among

  5. Upregulation of SOCS-3 and PIAS-3 impairs IL-12-mediated interferon-gamma response in CD56 T cells in HCV-infected heroin users.

    Directory of Open Access Journals (Sweden)

    Li Ye

    Full Text Available BACKGROUND: CD56(+ T cells are abundant in liver and play an important role in host innate immunity against viral infections, including hepatitis C virus (HCV infection, a common infection among heroin abusers. We thus investigated the in vivo impact of heroin use or heroin use plus HCV infection on the CD56(+ T cell frequency and function. METHODOLOGY/PRINCIPAL FINDINGS: A total of 37 heroin users with (17 or without (20 HCV infection and 17 healthy subjects were included in the study. Although there was no significant difference in CD56(+ T cell frequency in PBMCs among three study groups, CD56(+ T cells isolated from the heroin users had significantly lower levels of constitutive interferon-gamma (IFN-gamma expression than those from the normal subjects. In addition, when stimulated by interleukin (IL-12, CD56(+ natural T cells from HCV-infected heroin users produced significantly lower levels of IFN-gamma than those from the normal subjects. This diminished ability to produce IFN-gamma by CD56(+ T cells was associated with the increased plasma HCV viral loads in the HCV-infected heroin users. Investigation of the mechanisms showed that although heroin use or heroin use plus HCV infection had little impact on the expression of the key positive regulators (IL-12 receptors, STAT-1, 3, 4, 5, JAK-2, and TYK-2 in IL-12 pathway, heroin use or heroin use plus HCV infection induced the expression of suppressor of cytokine signaling protein-3 (SOCS-3 and protein inhibitors of activated STAT-3 (PIAS-3, two key inhibitors of IL-12 pathway. CONCLUSION/SIGNIFICANCE: These findings provide compelling in vivo evidence that heroin use or heroin use plus HCV infection impairs CD56(+ T cell-mediated innate immune function, which may account for HCV infection and persistence in liver.

  6. The anti-lymphoma activity of antiviral therapy in HCV-associated B-cell non-Hodgkin lymphomas: a meta-analysis.

    Science.gov (United States)

    Peveling-Oberhag, J; Arcaini, L; Bankov, K; Zeuzem, S; Herrmann, E

    2016-07-01

    Many epidemiological studies provide solid evidence for an association of chronic hepatitis C virus (HCV) infection with B-cell non-Hodgkin's lymphoma (B-NHL). However, the most convincing evidence for a causal relationship between HCV infection and lymphoma development is the observation of B-NHL regression after HCV eradication by antiviral therapy (AVT). We conducted a literature search to identify studies that included patients with HCV-associated B-NHL (HCV-NHL) who received AVT, with the intention to treat lymphoma and viral disease at the same time. The primary end point was the correlation of sustained virological response (SVR) under AVT with lymphoma response. Secondary end points were overall lymphoma response rates and HCV-NHL response in correlation with lymphoma subtypes. We included 20 studies that evaluated the efficacy of AVT in HCV-NHL (n = 254 patients). Overall lymphoma response rate through AVT was 73% [95%>confidence interval, (CI) 67-78%]. Throughout studies there was a strong association between SVR and lymphoma response (83% response rate, 95%>CI, 76-88%) compared to a failure in achieving SVR (53% response rate, 95%>CI, 39-67%, P = 0.0002). There was a trend towards favourable response for AVT in HCV-associated marginal zone lymphomas (response rate 81%, 95%>CI, 74-87%) compared to nonmarginal zone origin (response rate 71%, 95%>CI, 61-79%, P = 0.07). In conclusion, in the current meta-analysis, the overall response rate of HCV-NHL under AVT justifies the recommendation for AVT as first-line treatment in patients who do not need immediate conventional treatment. The strong correlation of SVR and lymphoma regression supports the hypothesis of a causal relationship of HCV and lymphomagenesis. PMID:26924533

  7. The test of hepatitis C virus antigen by ELISA for clinical diagnosis

    International Nuclear Information System (INIS)

    To provide a testing technique for early clinical diagnosis of HCV infection by detecting HCV antigen(HCAg) through testing serum samples by ELISA, HCV polyclonal antibodies were prepared from animals immunized by mutliepitope complex antigen of HCV expressed by E. coli. Using antibody sandwiched ELISA to detect the HCAg from serum samples, we analyzed the positive rate of HCAg and compared it with the findings of RT-PCR. The positive rate of HCAg was 53.7% from 95 serum samples of the HCAb positive cases; the positive rate of HCAg was 37.5% from 88 serum samples of serious hepatic damage cases, and 11.0% from 73 serum samples of high ALT but with negative HCAb. The results showed that HCAg was related with HCAb(r=0.5076,P<0.01). In 87.5% of the cases, both HCAg and HCV-RNA were positive as compared with RT-PCR. The ELISA method of HCVAg that we developed is a possible technique for early clinical diagnosis of HCV infection. (authors)

  8. Prioritization of high-cost new drugs for HCV: making sustainability ethical.

    Science.gov (United States)

    Craxì, L; Sacchini, D; Refolo, P; Minacori, R; Daloiso, V; Ricci, G; Bruno, R; Cammà, C; Cicchetti, A; Gasbarrini, A; Spagnolo, A G

    2016-03-01

    Hepatitis C virus (HCV) infection is a major health problem worldwide. Chronic HCV infection may in the long run cause cirrhosis, hepatic decompensation and hepatocellular carcinoma, with an ultimate disease burden of at least 350,000 deaths per year worldwide. The new generation of highly effective direct acting antivirals (DAA) to treat HCV infection brings major promises to infected patients in terms of exceedingly high rates of sustained virological response (SVR) but also of tolerability, allowing even the sickest patients to be treated. Even in the face of the excellent safety and efficacy and wide theoretical applicability of these regimens, their introduction is currently facing cost and access issues denying their use to many patients in need. Health systems in all countries are facing a huge problem of distributive justice, since while they should guarantee individual rights, among which the right to health in its broader sense, therefore not limited to healing, but extended to quality of life, they must also grant equal access to the healthcare resources and keep the distribution system sustainable. In the face of a disease with a relatively unpredictable course, where many but not of all chronically infected will eventually die of liver disease, selective allocation of this costly resource is debatable. In most countries the favorite solution has been a stratification of patients for prioritization of treatment, which means allowing Interferon-free DAA treatment only in patients with advanced fibrosis or cirrhosis, while keeping on hold persons with lesser stages of liver disease. In this report, we will perform an ethical assessment addressing the issues linked to access to new therapies, prioritization and eligibility criteria, analyzing the meaning of the term "distributive justice" and the different approaches that can guide us (individualistic libertarianism, social utilitarianism and egalitarianism) on this specific matter. Even if over time the

  9. Value of diagnosis on hepatitis C by ELISA-HCV core antigen detection%核心抗原酶联免疫检测在丙型肝炎病毒感染诊断中的价值

    Institute of Scientific and Technical Information of China (English)

    陈伟岳; 俞勇; 杜蓬

    2016-01-01

    目的探讨丙型肝炎病毒核心抗原( HCV-cAg)酶联免疫检测( ELISA)在丙型肝炎早期诊断中的应用价值。方法83例抗-HCV阳性、500例ALT异常但抗-HCV阴性血清同时进行HCV-cAg ELISA和HCV RT-PCR。结果83例抗-HCV阳性血清中HCV-cAg和HCV RNA阳性分别为33例和36例,其中32例共阳性;500例ALT异常但抗-HCV阴性的血清中有3例HCV-cAg和HCV RNA同为阳性。抗-HCV阳性和阴性血清HCV-cAg和HCV RNA检测结果符合率分别为94.0%和100%。结论 HCV-cAg ELISA敏感性与HCV RT-PCR类似,能够有效缩短窗口期,操作简便,费用低廉,在丙型肝炎早期诊断中具有很好的前景。%Objective To evaluate the clinically applied valve of HCV core antigen enzyme-linked immunosorbent assay ( HCV-cAg ELISA) for early diagnosis of hepatitis C.Methods Both HCV RNA and HCV-cAg ELISA were used to detect 83 cases of anti-HCV positive serum samples and 500 cases of anti-HCV negative but ALT abnormal serum samples.Results In the 83 cases of anti-HCV positive serum samples, 33 cases were detectable for HCV-cAg while 36 cases were detectable for HCV RNA, in which 32 cases were double positive for both HCV-cAg and HCV-RNA.In the 500 cases of anti-HCV negative but ALT abnormal serum sample, only 3 cases were detectable for both HCV-cAg and HCV RNA. The coincidence rates of the two methods for detecting the anti-HCV positive serum samples and anti-HCV negative but ALT abnormal serum samples were 94.0% and 100%, respectively.Conclusion The sensitivity and specificity of HCV-cAg ELISA is similar to that of HCV RT-PCR.The HCV-cAg ELISA has many advantages such as window-phase,decurtation, convenience and lower cost, which enable the assay a good clinically applied prospects for early diagnosis of hepatitis B.

  10. Immunization with Recombinant Adenoviral Vectors Expressing HCV Core or F Proteins Leads to T Cells with Reduced Effector Molecules Granzyme B and IFN-γ: A Potential New Strategy for Immune Evasion in HCV Infection.

    Science.gov (United States)

    Samrat, Subodh Kumar; Vedi, Satish; Singh, Shakti; Li, Wen; Kumar, Rakesh; Agrawal, Babita

    2015-01-01

    Multispecific, broad, and potent T cell responses have been correlated with viral clearance in hepatitis C virus (HCV) infection. However, the majority of infected patients develop chronic infection, suggesting that natural infection mostly leads to development of inefficient T cell immunity. Multiple mechanisms of immune modulation and evasion have been shown in HCV infection through various investigations. This study examined the generation and modulation of T cell responses against core and frameshift (F) proteins of HCV. A single immunization of mice with replication incompetent recombinant adenovirus vectors encoding for F or core antigens induces poor T cell responses and leads to generation of CD4+ and CD8+ T cells with low granzyme B (GrB) expression. These T cells have impaired GrB enzyme activity and are unable to kill peptide loaded target cells. The low intracellular expression of GrB is not due to degranulation of cytotoxic granules containing cytotoxic T cells. Addition of exogenous IL-2 in in vitro cultures leads to partial recovery of GrB production, whereas immunization with the Toll-like receptor (TLR) agonist poly I:C leads to complete restoration of GrB expression in both CD4+ and CD8+ T cells. Thus, a possible new strategy of T cell modulation is recognized wherein effector T cells are caused to be dysfunctional by HCV-derived antigens F or core, and strategies are also delineated to overcome this dysfunction. These studies are important in the investigation of prophylactic vaccine and immunotherapy strategies for HCV infection. PMID:26133045

  11. The impact of social factors on human immunodeficiency virus and hepatitis C virus co-infection in a minority region of Si-chuan, the People's Republic of China: a population-based survey and testing study.

    Directory of Open Access Journals (Sweden)

    Caiting Dong

    Full Text Available BACKGROUND: While many human immunodeficiency virus (HIV studies have been performed in Liangshan, most were focused only on HIV infection and based on a sampling survey. In order to fully understand HIV and hepatitis C virus (HCV prevalence and related risk factors in this region, this study implemented in 2009, included a survey, physical examination, HIV and HCV test in two towns. METHODS: All residents in two towns of the Butuo county were provided a physical examination and blood tests for HIV and HCV, and then followed by an interview for questionnaire. RESULTS: In total, 10,104 residents (92.4% were enrolled and 9,179 blood samples were collected for HIV and HCV testing, 6,072 were from individuals >14 years old. The rates of HIV, HCV, and HIV/HCV co-infection were 11.4%, 14.0%, and 7.7%, respectively for >14-year-old residents. The 25-34 yr age group had the highest prevalence of HIV, HCV, and HIV/HCV co-infections, reaching 24.4%, 26.2% and 16.0%, respectively. Overall, males had a much higher prevalence of all infections than females (HIV: 16.3% vs. 6.8%, HCV: 24.6% vs. 3.9%, HIV/HCV co-infected: 14.7% vs. 1.1%, respectively; P = 0.000. Approximately half of intravenous drug users tested positive for HIV (48.7% and 68.4% tested positive for HCV. Logistic regression analysis showed that five factors were significantly associated with HIV and HCV infection: gender (odds ratio [OR]  = 5.8, education (OR = 2.29; occupation (student as reference; farmer: OR = 5.02, migrant worker: OR = 6.12; drug abuse (OR = 18.0; and multiple sexual partners (OR = 2.92. Knowledge of HIV was not associated with infection. CONCLUSION: HIV and HCV prevalence in the Liangshan region is very serious and drug use, multiple sexual partners, and low education levels were the three main risk factors. The government should focus on improving education and personal health awareness while enhancing drug control programs.

  12. A Novel Fibrosis Index Comprising a Non-Cholesterol Sterol Accurately Predicts HCV-Related Liver Cirrhosis

    DEFF Research Database (Denmark)

    Ydreborg, Magdalena; Lisovskaja, Vera; Lagging, Martin;

    2014-01-01

    significance for liver fibrosis in 278 patients originally included in a multicenter phase III treatment trial for chronic HCV infection. A stepwise multivariate logistic model selection was performed with liver cirrhosis, defined as Ishak fibrosis stage 5-6, as the outcome variable. A new index, referred to...

  13. Predictors of psychopathological outcome during peg-interferon and ribavirin therapy in patients with chronic HCV-correlated hepatitis.

    Science.gov (United States)

    Dell'Osso, Bernardo; Prati, Gianmaria; Palazzo, M Carlotta; Rumi, Maria Grazia; Cavallaro, Flaminia; Aghemo, Alessio; Colombo, Massimo; Altamura, A Carlo

    2013-01-01

    Peg-interferon (Peg-IFN) and ribavirin (RBV) therapy is reported to induce psychiatric symptoms and syndromes in 20% of patients treated for Hepatitis C Virus (HCV) infection. Present study was aimed to quantify the phenomenon and assess the influence of psychiatric counseling over antiviral completion rate and the use of psychometric tools, in terms of prediction of psychopathological outcome. Ninety-six HCV patients were assessed, before antiviral treatment, by means of the Sheehan Disability Scale (SDS), Mood Disorder Questionnaire (MDQ), Symptom Checklist-90, and Internal State Scale (ISS). Sociodemographic and clinical variables and completion rate were collected. Binary logistic regression was performed to evaluate whether scores were predictive of psychiatric visit, development of psychiatric disorders, and need for treatment. Ninety-five patients (99%) completed antiviral treatment; 27 subjects (29%) needed psychiatric visit: among them, mood disorder was diagnosed in 15 (16%) and were pharmacologically treated. Baseline SDS and MDQ higher scores were found to be predictive of psychiatric visit [odds ratio (OR)=1.258, Pcounseling may be needed in almost 30% of HCV patients on antiviral treatment, with positive influence over the completion rate. Baseline higher scores at psychometric questionnaires-MDQ-in particular, predictors of psychopathological outcome during Peg-IFN and RBV therapy in patients with chronic HCV-correlated hepatitis reflecting individual functioning before starting antiviral therapy and positive history for mood disorders, seem to predict psychiatric visit, onset of mood episodes, and need for psychopharmacological treatment. Further investigation is warranted to confirm results. PMID:23276143

  14. Cyclosporine versus tacrolimus in patients with HCV infection after liver transplantation: Effects on virus replication and recurrent hepatitis

    Institute of Scientific and Technical Information of China (English)

    Philip Hilgard; Guido Gerken; Alisan Kahraman; Nils Lehmann; Cornelia Seltmann; Susanne Beckebaum; R Stefan Ross; Hideo A Baba; Massimo Malago; Christoph E Broelsch

    2006-01-01

    AIM: To determine the effects of the calcineurin inhibitors, cyclosporine and tacrolimus, on hepatitis C virus (HCV) replication and activity of recurrent hepatitis C in patients post liver transplantation.METHODS: The data of a cohort of 107 patients who received liver transplantation for HCV-associated liver cirrhosis between 1999 and 2003 in our center were retrospectively analyzed. The level of serum HCV-RNA and the activity of recurrent hepatitis were compared between 47 patients who received either cyclosporine or tacrolimus as the primary immunosuppressive agent and an otherwise similar immunosuppressive regimen which did not lead to biliary complications within the first 12mo after transplantation.RESULTS: HCV-RNA increased within 3 mo after transplantation but the differences between the cyclosporine group and the tacrolimus group were insignificant (P=0.49 at 12 mo). In addition, recurrent hepatitis as determined by serum transaminases and histological grading of portal inflammation and fibrosis showed no significant difference after 12 mo (P= 0.34).CONCLUSION: Cyclosporine or tacrolimus as a primary immunosuppressive agent does not influence the induction or severity of recurrent hepatitis in HCVinfected patients after liver transplantation.

  15. Cytokines, Lipid Peroxide and Nitric Oxide in Egyptian Hepatocellular Carcinoma on Top of HCV and HBV Infection

    Directory of Open Access Journals (Sweden)

    Osman E.E., Mabrouk F.M., Hassan H.A., Aboelyazed S.M

    2007-12-01

    Full Text Available Background and Aims: Many studies have shown the relative roles of hepatitis B and C viruses in hepato-carcinogenesis. The aim of this study is to define the independent and interactive roles of some cytokines namely, TNF , IL-6, IL-1 together with NO and TEARS in the genesis of HCC following the infection with such viruses. Patients and methods: Blood samples were taken from 58 patients with hepatocellular carcinoma and were divided into four groups: a 28 patients with HCV, b 10 patients with HBV, c 11 patients with B+C, d 9 patients without viral infection. In addition, 20 healthy subjects served as control group for each, TNF , IL-6, and IL-1 were measured using ELISA technique, in addition to NO and TBARs using chemical methods. Results: Patients with coinfection B-C viral infection showed the highest levels in studied parameters. Patients with HCV and HBV separately showed more or less similar results. However, patients without viral infection showed the least higher levels comparing to the control group. Conclusion: Cytokines in addition to NO and TEARS have a definite role in hepatic carcinogenesis. Coinfection with the two viruses carries a synergistic risk factor of hepatocellular carcinoma development. Depending on the results of the studied parameters HCV did not show predominancy on HBV. Further studies are needed to clarify the exact mechanism of carcinogenesis especially in HCV patients.

  16. Pharmacokinetics and antiviral activity of PHX1766, a novel HCV protease inhibitor, using an accelerated Phase I study design

    NARCIS (Netherlands)

    D.M. Hotho (Daphne); J. Bruijne (Joep); N. O'Farrell; T. Boyea (Teresa); J. Li (Jianke); M. Bracken (Michele); X. Li (Xin); D. Campbell (David); H.-P. Guler (Hans-Peter); C.J. Weegink (Christine); J. Schinkel (Janke); R. Molenkamp (Richard); J. Van De Wetering De Rooij (Jeroen); A.A. Vliet (Andre); H.L.A. Janssen (Harry); R.J. de Knegt (Robert); H.W. Reesink (Henk)

    2012-01-01

    textabstractBackground: PHX1766 is a novel HCV NS3/4 protease inhibitor with robust potency and high selectivity in replicon studies (50% maximal effective concentration 8 nM). Two clinical trials investigated the safety, tolerability, pharmacokinetics and antiviral activity of PHX1766 in healthy vo

  17. Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016.

    Science.gov (United States)

    Puri, Pankaj; Saraswat, Vivek A; Dhiman, Radha K; Anand, Anil C; Acharya, Subrat K; Singh, Shivaram P; Chawla, Yogesh K; Amarapurkar, Deepak N; Kumar, Ajay; Arora, Anil; Dixit, Vinod K; Koshy, Abraham; Sood, Ajit; Duseja, Ajay; Kapoor, Dharmesh; Madan, Kaushal; Srivastava, Anshu; Kumar, Ashish; Wadhawan, Manav; Goel, Amit; Verma, Abhai; Shalimar; Pandey, Gaurav; Malik, Rohan; Agrawal, Swastik

    2016-06-01

    India contributes significantly to the global burden of HCV. While the nucleoside NS5B inhibitor sofosbuvir became available in the Indian market in March 2015, the other directly acting agents (DAAs), Ledipasvir and Daclatasvir, have only recently become available in the India. The introduction of these DAA in India at a relatively affordable price has led to great optimism about prospects of cure for these patients as not only will they provide higher efficacy, but combination DAAs as all-oral regimen will result in lower side effects than were seen with pegylated interferon alfa and ribavirin therapy. Availability of these newer DAAs has necessitated revision of INASL guidelines for the treatment of HCV published in 2015. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. The availability of combination DAA therapy has simplified therapy of HCV with decreased reliance of evaluation for monitoring viral kinetics or drug related side effects. PMID:27493460

  18. Acute hepatitis C virus (HCV infection in the setting of HIV coinfection: a single-centre 10-year follow-up

    Directory of Open Access Journals (Sweden)

    Patrick Ingiliz

    2014-11-01

    Full Text Available Introduction: Acute hepatitis C virus (HCV infection has emerged as a major cause of morbidity in the HIV-infected population. Most guidelines recommend early treatment with pegylated interferon and ribavirin due to higher cure rates. The impact of acute HCV and its treatment on the outcome of the HIV-infected population is unknown. With new treatment options for HCV, early treatment of acute HCV has to be questioned. Here, we report a long-term analysis on patients with acute HCV. Methods: Retrospective analysis from an outpatient clinic from Berlin. All patients with the diagnosis of acute HCV according to The European AIDS Treatment Network (NEAT criteria were included in the database at their date of HCV diagnosis and followed-up until the last medical contact. Demographic data was taken from the medica