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Sample records for ampliscreen hcv test

  1. [Comparison of eight screening tests for ant-HCV antibody].

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    Deguchi, Matsuo; Kagita, Masanori; Yamashita, Naoko; Nakano, Takasi; Tahara, Kazuko; Asari, Seishi; Iwatani, Yoshinori

    2002-09-01

    We compared eight HCV screening tests for detection of anti-HCV antibody; Ortho Quick Chaser HCV Ab (QC), Ortho HCV Ab ELISA III (ELISA), Ortho HVC Ab PA test III (PA), Lumipulse II Ortho HCV (LUMI), IMx HCV.DAINAPACKII (IMx), ARCHITECT HCV (ARCH), Immucheck.F-HCV C50 Ab (Immu), RANREAM HCV Ab Ex II (RAN). Sera from six hundred patients were examined by these eight screening tests. The positive rates of the eight screening tests were from 9.0% to 13.2%. Forty-five sera showed discrepant results between the eight screening tests, and about half of them showed weak positive reaction and/or false positive. Twenty-five of the forty-five sera were negative for ant-HCV antibody in the CHIRON RIBA III confirmatory test, and forty-four of them were negative for HCV-RNA in the PCR method. The agreement rates between the two reagents were from 95.5% to 99.2%, but were not always high between the two reagents that used similar antigen. The specificities and sensitivities evaluated by using the RIBA III confirmatory test were excellent in ELISA, LUMI, IMx, ARCH and Immu. Three BBI seroconversion panels were used to compare the positive readings in the initial stage of HCV infection by eight screening tests. ELISA and ARCH showed the earliest positive readings, and then IMx, LUMI = RAN, PA, QC and Immu in this order. These findings indicate that ELISA and ARCH were the most excellent in the sensitivity, specificity and early diagnosis of HCV infection. However, we must pay attention to the weak positive reaction in the screening tests, because there is a possibility of "false positive".

  2. 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.

  3. 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

  4. 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

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

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    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.

  6. Point-of-care testing for HCV infection: recent advances and implications for alternative screening.

    Science.gov (United States)

    Parisi, Maria Rita; Soldini, Laura; Vidoni, Gianmarino; Mabellini, Chiara; Belloni, Teresa; Brignolo, Livia; Negri, Silvia; Schlusnus, Karin; Dorigatti, Fernanda; Lazzarin, Adriano

    2014-10-01

    Over the last few years, hepatitis C virus (HCV) infection has emerged as one of the most significant causes of chronic liver disease worldwide, with an estimated prevalence ranging from 2.2 to 3.0%. In Italy, approximately 2% of subjects are infected with HCV. Considering that acute HCV infection is usually asymptomatic, early diagnosis is rare. Those people who develop chronic infection, even though undiagnosed, may suffer serious liver damage, making chronic HCV infection a major health problem. New initiatives are needed to identify a submerged portion of patients with chronic viral hepatitis and to propose controls and antiviral treatments to avoid the progression to liver cirrhosis or hepatocellular carcinoma (HCC). Since January 2011, the Infectious Diseases Department of San Raffaele Scientific Institute in Milan has been carrying out a prevention program called "EASY test project", using a new oral test, the OraQuick® HCV rapid antibody test (OraSure technologies, Inc.). The main objective of the project is to evaluate the acceptability of an alternative, free and anonymous HCV test offer, available in different settings (Points of Care, STDs Prevention clinics and General Practitioner clinics). From January 2011 to April 2014, 29,600 subjects were approached to inform them about HCV infection and other sexually transmitted diseases; 4,507 (15.2% of the contacted subjects) of them, total eligible volunteers, performed HCV tests on saliva and completed the interview in the alternative POCTs. Twenty-seven subjects (0.6% of the total) turned HCV oral test reactive (27/4.507) during the evaluation period; all of them were confirmed by conventional test. All 27 patients were asymptomatic and without a history of HCV-re- lated symptoms. The results from this analysis suggest that the promotion of alternative HCV test screening has not yet been fully developed as a strategy to increase levels of HCV testing among people at risk for HCV infection. Increasing

  7. 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.

  8. 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

  9. Clinical performance of the new Roche COBAS (R) TaqMan HCV test and high pure system for extraction, detection and quantitation of HCV RNA in plasma and serum

    NARCIS (Netherlands)

    H.C. Gelderblom; S. Menting; M.G. Beld

    2006-01-01

    We evaluated the Roche COBAS (R) TaqMan HCV Test For Use With The High Pure System (TaqMan HPS; Roche Diagnostics), for the extraction, detection and quantitation of hepatitis C virus (HCV) RNA in serum or plasma of HCV-infected individuals. The TaqMan HPS is a real-time PCR assay with a reported li

  10. 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

  11. [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

  12. 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.

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

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    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...

  14. Analysis of Anti-HCV Test Results Using ELISA Reagents from Different Companies%多厂家抗-HCV ELISA检测结果分析

    Institute of Scientific and Technical Information of China (English)

    安社刚; 卢新明; 杨来智

    2011-01-01

    探讨多厂家抗-HCV ELISA试剂检测结果不一致的原因.选用4个国产厂家和2个进口厂家试剂对175份样品进行抗-HCV检测,并对其中17份检测结果不一致的样品和1份6个厂家试剂检测均为弱阳性的样品用抗-HCV ELISA分片段试剂进行检测,用SPSS13.0软件对检测结果进行统计分析.结果显示,6个厂家试剂对175份标本的检测结果,同为阴性85份,同为阳性38份,有52份样品检测结果不一致.18份结果不一致的样本用分片段试剂测定的结果为:Ⅰ试剂的假阴性率为75.00%(9/12);Ⅱ试剂的假阴性率为25.00%(3/12);Ⅲ试剂的假阴性率为66.67%(8/12);Ⅳ试剂的假阴性率为33.33%(4/12);Ⅴ试剂的假阴性率为58.33%(7/12);Ⅵ试剂的假阴性率为33.33%(4/12).采用II+V的组合实验检测假阴性率为8.33%(1/12),有很明显的降低.结论:试剂盒包被抗原成份的差异可能是检测结果不一致的重要原因,选择包被抗原成份互补的试剂盒分别进行初筛和复检实验是减少假阴性结果,保障血液安全的重要手段.%To explore the reason of conflict test results by using anti-HCV ELISA reagents from different companies, 175 serum samples were tested by using anti-HCV reagents from four domestic and two foreign companies.17 samples with conflicted results and 1 sample with weak positive result in these 175 samples were tested by using anti-HCV sub-fragment ELISA reagents respectively. The results were statistically analyzed with SPSS13.0 software. The results showed that 85 samples were negative, 38 were positive, and 52 had discordant results among the 175 samples tested by using reagents from 6 different companies. The results of 18 discordant resulting samples tested by anti-HCV sub-fragment reagent showed that the false negative rate of reagent I, Ⅱ, Ⅲ, Ⅳ, V and Ⅵ were 75% (9/12), 25% (3/12), 66.67% (8/12), 33.33% (4/12), 58.33% (7/12), 33.33% (4/12), respectively. The false negative rate of

  15. 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.

  16. Development of a rapid phenotypic test for HCV protease inhibitors with potential use in clinical decisions.

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    Pessoa, Luciana Santos; Vidal, Luãnna Liebscher; Costa, Emmerson C B da; Abreu, Celina Monteiro; Cunha, Rodrigo Delvecchio da; Valadão, Ana Luiza Chaves; Santos, André Felipe Dos; Tanuri, Amilcar

    2016-01-01

    Approximately 185 million people worldwide are chronically infected with hepatitis C virus (HCV). The first-wave of approved NS3 protease inhibitors (PIs) were Telaprevir and Boceprevir, which are currently discontinued. Simeprevir is a second-wave PI incorporated into the Brazilian hepatitis C treatment protocol. Drug resistance plays a key role in patients' treatment regimen. Here, we developed a simple phenotypic assay to evaluate the impact of resistance mutations in HCV NS3 protease to PIs, using a protein expression vector containing wild type NS3 protease domain and NS4A co-factor. We analyzed the impact of five resistance mutations (T54A, V36M, V158I, V170I and T54S+V170I) against Telaprevir, Boceprevir and Simeprevir. Protein purifications were performed with low cost methodology, and enzymatic inhibition assays were measured by FRET. We obtained recombinant proteases with detectable activity, and IC50 and fold change values for the evaluated PIs were determined. The variant T54A showed the highest reduction of susceptibility for the PIs, while the other four variants exhibited lower levels of reduced susceptibility. Interestingly, V170I showed 3.2-fold change for Simeprevir, a new evidence about this variant. These results emphasize the importance of enzymatic assays in phenotypic tests to determine which therapeutic regimen should be implemented. PMID:27575432

  17. Development of a rapid phenotypic test for HCV protease inhibitors with potential use in clinical decisions

    Science.gov (United States)

    Pessoa, Luciana Santos; Vidal, Luãnna Liebscher; da Costa, Emmerson C.B.; Abreu, Celina Monteiro; da Cunha, Rodrigo Delvecchio; Valadão, Ana Luiza Chaves; dos Santos, André Felipe; Tanuri, Amilcar

    2016-01-01

    Abstract Approximately 185 million people worldwide are chronically infected with hepatitis C virus (HCV). The first-wave of approved NS3 protease inhibitors (PIs) were Telaprevir and Boceprevir, which are currently discontinued. Simeprevir is a second-wave PI incorporated into the Brazilian hepatitis C treatment protocol. Drug resistance plays a key role in patients' treatment regimen. Here, we developed a simple phenotypic assay to evaluate the impact of resistance mutations in HCV NS3 protease to PIs, using a protein expression vector containing wild type NS3 protease domain and NS4A co-factor. We analyzed the impact of five resistance mutations (T54A, V36M, V158I, V170I and T54S+V170I) against Telaprevir, Boceprevir and Simeprevir. Protein purifications were performed with low cost methodology, and enzymatic inhibition assays were measured by FRET. We obtained recombinant proteases with detectable activity, and IC50 and fold change values for the evaluated PIs were determined. The variant T54A showed the highest reduction of susceptibility for the PIs, while the other four variants exhibited lower levels of reduced susceptibility. Interestingly, V170I showed 3.2-fold change for Simeprevir, a new evidence about this variant. These results emphasize the importance of enzymatic assays in phenotypic tests to determine which therapeutic regimen should be implemented. PMID:27575432

  18. Increased Uptake of HCV Testing through a Community-Based Educational Intervention in Difficult-to-Reach People Who Inject Drugs: Results from the ANRS-AERLI Study

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    Roux, Perrine; Rojas Castro, Daniela; Ndiaye, Khadim; Debrus, Marie; Protopopescu, Camélia; Le Gall, Jean-Marie; Haas, Aurélie; Mora, Marion; Spire, Bruno; Suzan-Monti, Marie; Carrieri, Patrizia

    2016-01-01

    Aims The community-based AERLI intervention provided training and education to people who inject drugs (PWID) about HIV and HCV transmission risk reduction, with a focus on drug injecting practices, other injection-related complications, and access to HIV and HCV testing and care. We hypothesized that in such a population where HCV prevalence is very high and where few know their HCV serostatus, AERLI would lead to increased HCV testing. Methods The national multisite intervention study ANRS-AERLI consisted in assessing the impact of an injection-centered face-to-face educational session offered in volunteer harm reduction (HR) centers (“with intervention”) compared with standard HR centers (“without intervention”). The study included 271 PWID interviewed on three occasions: enrolment, 6 and 12 months. Participants in the intervention group received at least one face-to-face educational session during the first 6 months. Measurements The primary outcome of this analysis was reporting to have been tested for HCV during the previous 6 months. Statistical analyses used a two-step Heckman approach to account for bias arising from the non-randomized clustering design. This approach identified factors associated with HCV testing during the previous 6 months. Findings Of the 271 participants, 127 and 144 were enrolled in the control and intervention groups, respectively. Of the latter, 113 received at least one educational session. For the present analysis, we selected 114 and 88 participants eligible for HCV testing in the control and intervention groups, respectively. In the intervention group, 44% of participants reported having being tested for HCV during the previous 6 months at enrolment and 85% at 6 months or 12 months. In the control group, these percentages were 51% at enrolment and 78% at 12 months. Multivariable analyses showed that participants who received at least one educational session during follow-up were more likely to report HCV testing

  19. Purification of HCV Multi-epitope and Polyclonal Antibody and Test of HCV-Ag%HCV多表位多克隆抗体的纯化及HCV-Ag的检测

    Institute of Scientific and Technical Information of China (English)

    傅涛; 郭宏雄; 李卫中; 李琦涵

    2010-01-01

    目的:制备并纯化HCV复合多表位多克隆抗体,探讨其用于丙型肝炎抗原检测的潜在可行性.方法:将人工合成的HCV复合多表位抗原在大肠杆菌中表达融合蛋白后免疫小鼠分析表达产物的免疫特异性及免疫原性,免疫家兔获取多克隆抗体,利用盐析和亲和柱纯化多克隆抗体,利用该抗体用双抗夹心法检测HCV-Ag.结果:融合蛋白能在原核表达系统中高效表达,并可诱发小鼠及家兔产生高滴度的特异性HCV抗体,该HCV多表位复合抗原多克隆抗体,在用ELISA法检测HCV-Ag中表现出较高的灵敏性(90.63%)及特异性(78.13%).结论:通过盐析和亲和柱可高效纯化HCV复合多表位多克隆抗体,纯化后的抗体用ELISA双抗体夹心法检测HCV-Ag具有灵敏、特异、快速的优点,有望用于HCV的抗原检测.

  20. 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...

  1. 抗-HCV多表位抗体在检测HCV抗原中的应用%Application of HCV Multi-epitope Antibody in Test for HCV Antigen

    Institute of Scientific and Technical Information of China (English)

    谢忠平; 龙润乡; 宋霞; 李华; 李文忠; 熊秋霞; 洪超; 崔萍芳; 李琦涵

    2006-01-01

    目的应用丙型肝炎病毒多表位抗体,探索从血浆或血清样品中检测丙型肝炎病毒抗原(HCAg)的可能性,为献血员筛选及临床早期诊断提供检测方法.方法利用原核系统表达的丙型肝炎病毒(HCV)7个高度保守区基因的多表位复合抗原免疫动物,制备抗-HCV多克隆抗体,采用ELISA双抗体夹心法检测血浆或血清中的HCAg,并与RT-PCR法进行比较.结果制备的抗-HCV多表位复合抗原多克隆抗体,在用ELISA法检测HCAg中表现出较高的特异性及灵敏性,Cutoff值为0.239,批内CV值为5.60%~6.65%,批间CV值为7.80%.与RT-PCR比较,相关系数为0.816,灵敏度为88.89%,特异度为96.30%,一致性为95.24%,调整一致性为90.82%,阳性预测值为80.00%,阴性预测值为98.11%.HCAg检出率与美国ORTHO公司HCV-C抗原检测试剂盒差异无显著意义(P=0.06).结论用HCV多表位复合抗原制备的多克隆抗体,采用ELISA双抗体夹心法检测HCAg,具有灵敏、特异、快速的优点,有望开发成为HCAg诊断试剂盒.

  2. 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...

  3. 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...... 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 their characteristics were compared with those of patients who were still aviraemic. Logistic regression was used to identify factors associated with HCV recurrence. RESULTS: Of 191 eligible patients, 35 [18.3%; 95% confidence interval (CI) 12.8-23.8%] had HCV recurrence. Thirty-three (94.3%) were injecting drug users...

  4. Study on the diagnosis value of combination of HCV-cAg and anti-HCV in HCV infection%HCV-cAg和HCV-Ab联合检测对HCV感染诊断价值的研究

    Institute of Scientific and Technical Information of China (English)

    林俊填; 余晋林; 伍伟健; 陈展泽; 龚道元

    2015-01-01

    Objective To explore the clinical value of combination of HCV-cAg and anti-HCV detection in HCV infection. Methods The serum samples from outpatients and inpatients were detected for HCV-cAg,anti-HCV and HCV-RNA. The quanti-tative real-time PCR was applied to detect HCV-RNA,and enzyme-linked immunosorbent assay (ELISA) kits were utilized to test anti-HCV and HCV-cAg). Result The sensitivity and specificity of anti-HCV detection were 90.91% and 99.17% respectively, and that of HCV-cAg were 70.25%and 100%respectively. Notably,the sensitivity(99.17%) and specificity(99.17%) increased sig-nificantly in case of combinational detection method. In addition,no consistency between the results of anti-HCV and HCV-cAg was detected. Conclusion Combination detection of anti-HCV and HCV-cAg was recommended because of its remarkable advan-tage in screening and diagnosis of HIV infection.%目的:探讨HCV-cAg和HCV-Ab两个指标联合检测对HCV感染的临床价值。方法对门诊和住院患者血液标本进行HCV-cAg、HCV-Ab 及HCV-RNA联合检测,采用实时荧光定量 PCR 法检测 HCV-RNA,采用酶联免疫吸附法(ELISA)检测试剂盒检测HCV-Ab和HCV-cAg。结果 HCV-Ab检测的灵敏度和特异度分别为90.91%和99.17%;HCV-cAg检测的灵敏度和特异度分别为70.25%和100%,两者的特异度相近,但是HCV-Ab检测的灵敏度比HCV-cAg的要高。两者联合检测时灵敏度和特异度分别为99.17%和99.17%,灵敏度明显增加。此外,HCV-Ab和HCV-cAg两者之间的检测结果无一致性。结论 HCV-Ab和HCV-cAg检测相互间无法替代,将抗-HCV和HCV-cAg两种指标结合起来检测,对临床上提高HCV感染的筛查和诊断具有重要的价值。

  5. HCV-cAg、HCV-RNA及HCV-Ab联合检测降低丙型肝炎的误诊率%Joint detection of HCV-cAg,HCV-RNA and HCV-Ab in decreasing misdiagnosis rate of hepatitis C

    Institute of Scientific and Technical Information of China (English)

    严海燕; 欧阳颖; 刘晓强; 任燕飞; 罗晓红

    2012-01-01

    目的:探讨丙型肝炎病毒总核心抗原、丙型肝炎RNA及抗丙型肝炎病毒抗体联合检测在丙型肝炎诊断中的应用价值.方法:对62例丙型肝炎患者阳性和64例HCV-RNA阴性的健康对照组血液标本同时采用RT-PCR定量检测HCV-RNA,时间分辨免疫荧光分析法检测HCV-Ab,和ELISA法检测HCV-cAg.结果:HCV-cAg检测方法敏感性为32.25%,特异性为100%,HCV-Ab检测方法的敏感性是92.0%,特异性是68.8%,联合检测的敏感性是96.8%,特异性是68.8%.结论:联合运用HCV-Ab和HCV-cAg或HCV-Ab和HCV-RNA,能有效降低单独使用HCV-Ab检测的误诊率.%Objective :To explore the diagnostic value of HCV RNA, the core antigen of HCV, HCV antibody in serum of patients with hepatitis C. Methods: Serum from 62 HCV RNA positive and 64 HCV RNA negative outpatients and inpatients were collected to detect the HCV antibody, HCV - RNA and HCV - cAg by time - resolved im-muno - fluorometric assay, RT - PCR and ELISA respectively. Results-. The sensitivity and specificity of HCV -cAg detection were 32. 25% and 100% respectively, while those of HCV - Ab detection were 92. 0% and 68. 8% respectively, those of joint detection were 96. 8% and 68. 8% respectively. Conclusion: Combination of anti HCV with HCV -cAg, or anti HCV with HCV RNA could effectively reduce the miss diagnosis rate, as compared with detecting anti HCV alone. All these suggested that HCV - cAg detection can indicate HCV replication, and can be used as supplementary indicators in routine testing.

  6. Rheumatoid Case with HCV Infection

    Directory of Open Access Journals (Sweden)

    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

  7. Occult HCV in Egyptian volunteer blood donors

    Directory of Open Access Journals (Sweden)

    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.

  8. ELISA in serodiagnosis of HCV infection.

    Science.gov (United States)

    Pillot, J; Rioche, M; Lazizi, Y

    1994-07-01

    A high level of anti-HCV is generally associated with viral replication and the number of recognized epitopes appears to be correlated with the viral charge. Nevertheless, the absence of detectable antibodies in about 60% of patients during the acute phase of the disease and in 10% of chronically infected (generally immunocompromised subjects) are heavy handicaps for HCV serology. Moreover, low levels of anti-HCV antibodies can persist after complete recovery, and HCV viremia does not appear to be associated with the presence of a special antibody specificity. The immunoblots presented as 'confirmatory test' always appear to be less sensitive than the screening tests and therefore are unable to discriminate between post-infection antibodies and false-positive reactions, as rare as they can be. In these cases, as in non-responder patients, PCR appears essential. The possible reasons of immune response limitations and the possible improvements of HCV serology are discussed. PMID:7522020

  9. 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.

  10. 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

    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 1940 HCV Ab-positive patients, 1496 (77%) were serum HCV RNA positive. Injection drug users (IDUs) were less likely to have spontaneously cleared HCV than were homosexual men (20% vs. 39%; adjusted odds ratio [aOR], 0.36 [95% confidence interval {CI}, 0.24-0.53]), whereas patients positive...

  11. Frequent HCV reinfection and superinfection in a cohort of injecting drug users in Amsterdam

    NARCIS (Netherlands)

    T.J.W. van de Laar; R. Molenkamp; C. van den Berg; J. Schinkel; M.G.H.M. Beld; M. Prins; R.A. Coutinho; S.M. Bruisten

    2009-01-01

    Background/Aims:This study investigates the occurrence of HCV reinfection and superinfection among HCV seroconverters participating in the Amsterdam Cohort Studies among drug users from 1985 through 2005. Methods: HCV seroconverters (n = 59) were tested for HCV RNA at five different time points: the

  12. 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

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

    OpenAIRE

    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...

  14. [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

  15. PML tumor suppressor protein is required for HCV production

    Energy Technology Data Exchange (ETDEWEB)

    Kuroki, Misao [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan); Research Fellow of the Japan Society for the Promotion of Science (Japan); Center for AIDS Research, Kumamoto University, Kumamoto 860-0811 (Japan); Ariumi, Yasuo, E-mail: ariumi@kumamoto-u.ac.jp [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan); Center for AIDS Research, Kumamoto University, Kumamoto 860-0811 (Japan); Hijikata, Makoto [Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606-8507 (Japan); Ikeda, Masanori; Dansako, Hiromichi [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan); Wakita, Takaji [Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640 (Japan); Shimotohno, Kunitada [Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba 272-8516 (Japan); Kato, Nobuyuki [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer PML tumor suppressor protein is required for HCV production. Black-Right-Pointing-Pointer PML is dispensable for HCV RNA replication. Black-Right-Pointing-Pointer HCV could not alter formation of PML-NBs. Black-Right-Pointing-Pointer INI1 and DDX5, PML-related proteins, are involved in HCV life cycle. -- Abstract: PML tumor suppressor protein, which forms discrete nuclear structures termed PML-nuclear bodies, has been associated with several cellular functions, including cell proliferation, apoptosis and antiviral defense. Recently, it was reported that the HCV core protein colocalizes with PML in PML-NBs and abrogates the PML function through interaction with PML. However, role(s) of PML in HCV life cycle is unknown. To test whether or not PML affects HCV life cycle, we examined the level of secreted HCV core and the infectivity of HCV in the culture supernatants as well as the level of HCV RNA in HuH-7-derived RSc cells, in which HCV-JFH1 can infect and efficiently replicate, stably expressing short hairpin RNA targeted to PML. In this context, the level of secreted HCV core and the infectivity in the supernatants from PML knockdown cells was remarkably reduced, whereas the level of HCV RNA in the PML knockdown cells was not significantly affected in spite of very effective knockdown of PML. In fact, we showed that PML is unrelated to HCV RNA replication using the subgenomic HCV-JFH1 replicon RNA, JRN/3-5B. Furthermore, the infectivity of HCV-like particle in the culture supernatants was significantly reduced in PML knockdown JRN/3-5B cells expressing core to NS2 coding region of HCV-JFH1 genome using the trans-packaging system. Finally, we also demonstrated that INI1 and DDX5, the PML-related proteins, are involved in HCV production. Taken together, these findings suggest that PML is required for HCV production.

  16. 不同HCV相关疾病患者血清抗HCV和HCV RNA检测的比较研究%Comparative Study on Detection of Serum anti-HCV and HCV RNA in HCV Related Diseases

    Institute of Scientific and Technical Information of China (English)

    刘伟平; 殷明刚

    2013-01-01

    目的::探讨不同HCV感染疾病患者血清抗HCV和HCV RNA的阳性率,以指导临床诊治相应疾病。方法:收集我院HCV感染患者血清标本共165例,采用ELISA法检测血清抗HCV,利用实时荧光定量PCR技术检测HCV RNA。结果:165例HCV感染患者血清抗HCV总阳性率为97.6%,高于HCV RNA阳性率(72.7%)(P<0.05)。肝硬化组和肝癌组HCV RNA阳性率分别为80.9%和82.9%,高于慢性丙型肝炎组阳性率(63.9%)(P<0.05)。结论:联合检测抗HCV和HCV RNA,有助于HCV感染相关疾病的临床诊断、疗效观察及预后判断。%Objective:The significance of testing serum anti-HCV and HCV RNA in HCV infection patients was discussed for guiding diagnosis and treatment of diseases.Methods:165 cases were collected from HCV infection patients.ELISA was used for assaying anti-HCV and real-time quantitative PCR was employed for determination of HCV RNA.Results:The total positive rate of serum anti-HCV(n=165) was 97.6%,which was higher than that of HCV RNA(72.7%).The positive rate of HCV RNA in liver cirrhosis and liver cancer group were 80.9%and 82.9%,respectively,higher than the one in chronic hepatitis C group 63.9%(P<0.05).Conclusion:The combination testing of anti-HCV and HCV RNA is helpful to the clinical diagnosis,observation of curative effect and prognosis judgment of HCV related diseases.

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

    Science.gov (United States)

    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

  18. HCV-Ab、HCV-cAg和HCV-RNA联合检测的临床价值

    Institute of Scientific and Technical Information of China (English)

    顾娟; 孙明忠

    2014-01-01

    目的:评价丙型肝炎病毒抗体(HCV-Ab)、丙型肝炎病毒核心抗原(HCV-cAg)以及HCV-RNA联合检测在HCV诊断中的应用价值。方法采用ELISA法对2023例输血和手术前住院患者的血液标本进行 HCV-Ab和 HCV-cAg的测定,并对阳性标本采用RT-PCR法进行HCV-RNA的测定。结果2023例筛查标本中 HCV-Ab(+)55例,其中 HCV-cAg (+)30例, HCV-RNA(+)40例;1968例HCV-Ab(-)的样本中检出 HCV-cAg(+)9例,其中 HCV-RNA (+)7例,HCV-cAg 与 HCV-RNA 符合率为83.0%(39/47)。结论 HCV-Ab检测结合HCV-cAg或者 HCV-RNA检测可以有效缩短 HCV的窗口期,降低漏检率。对于条件受限的基层医院 HCV-cAg 可以作为HCV-Ab常规检测的补充指标,提高检出率。

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Establishment of the method of nucleic acids amplification test for HCV/HZV-1 ofpooled source plasma%原料血浆混样HCV/HIV-1核酸检测的方法学研究

    Institute of Scientific and Technical Information of China (English)

    白坚石; 王威; 朱文斯

    2003-01-01

    目的建立原料血浆混浆核酸检测方法.方法以国产HCV和HIV核酸扩增(PCR)荧光定量检测试剂进行WHO标准品的灵敏度、重现性和精密度实验,并对19196份国内原料血浆进行HCV RNA和HIV-1 RNA核酸扩增分析.结果扩增系统能够确保高拷贝数(200 IU/ml)标准品核酸的检出率,对于<100 IU/ml的低拷贝数标准品核酸检出率逐渐降低;受检原料血浆样本没有检出HCV RNA和HIV-1 RNA阳性.结论核酸扩增方法适用于原料血浆病毒筛查.

  1. 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

  2. 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.

  3. Epidemiology of HCV infection.

    Science.gov (United States)

    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

  4. 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

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

    OpenAIRE

    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...

  6. Lysosomotropic agents as HCV entry inhibitors

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    Nawaz Zafar

    2011-04-01

    Full Text Available Abstract HCV has two envelop proteins named as E1 and E2 which play an important role in cell entry through two main pathways: direct fusion at the plasma membrane and receptor-mediated endocytosis. Fusion of the HCV envelope proteins is triggered by low pH within the endosome. Lysosomotropic agents (LA such as Chloroquine and Ammonium chloride (NH4Cl are the weak bases and penetrate in lysosome as protonated form and increase the intracellular pH. To investigate the antiviral effect of LA (Chloroquine and NH4Cl on pH dependent endocytosis, HCV pseudoparticles (HCVpp of 1a and 3a genotype were produced and used to infect liver cells. The toxicological effects of Chloroquine and NH4Cl were tested in liver cells through MTT cell proliferation assay. For antiviral screening of Chloroquine and NH4Cl, liver cells were infected with HCVpp of 3a and 1a genotype in the presence or absence of different concentrations of Chloroquine and NH4Cl and there luciferase activity was determined by using a luminometer. The results demonstrated that Chloroquine and NH4Cl showed more than 50% reduction of virus infectivity at 50 μM and 10 mM concentrations respectively. These results suggest that inhibition of HCV at fusion step by increasing the lysosomal pH will be better option to treat chronic HCV.

  7. HCV Virus and Lymphoid Neoplasms

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    Yutaka Tsutsumi

    2011-01-01

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

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

    Science.gov (United States)

    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

  9. Sieroprevalenza di infezione da HBV e HCV tra pazienti in dialisi

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    Rosa Anna Leone

    2003-12-01

    Full Text Available The aim of the present study was to investigate the seroprevalence of HBV and HCV among dialysis patients in the Lamezia Terme (CZ area during the period 1999-2002. Sera from 63 patients in haemodialysis (HD and 10 patients in peritoneal dialysis (PD were analyzed with a follow-up every three months for HBsAg, HBcAb, HBsAb, anti-HCV and anti-HIV (Elisa Test,AxSYM,Abbott;we analyzed reactive sera for anti-HCV by using supplemental test (RIBA Test, Ortho; we also looked for viremia (RT-PCR Amplicor, Roche Diagnostics and HCV genotypes (Inno-Lipa HCV II, Innogenetics.The results show that, among the HD patients, 3 were HBsAg positive (Chronic Infection and 7 HBcAb and HBsAb positive/HBsAg negative (Passed Infection; 14 individuals were anti-HCV positive. No patients in PD were positive for HBV and HCV markers.The prevalence of chronic HBV infection was 4.8% (instead of 3% in other Dialysis Units, that of anti-HCV positive was 22% (in others 24%- 33%; among anti-HCV positive patients, the HCV-RNA prevalence was 79% (instead of 80%; the most recurrent HCV genotype was 2a/2c (instead of 1b in general population.These findings lead us to hypothesize that the environmental transmission in the dialysis setting is tightly correlated to the risk of HBV and HCV infection.

  10. HCV genotyping from NGS short reads and its application in genotype detection from HCV mixed infected plasma.

    Science.gov (United States)

    Qiu, Ping; Stevens, Richard; Wei, Bo; Lahser, Fred; Howe, Anita Y M; Klappenbach, Joel A; Marton, Matthew J

    2015-01-01

    Genotyping of hepatitis C virus (HCV) plays an important role in the treatment of HCV. As new genotype-specific treatment options become available, it has become increasingly important to have accurate HCV genotype and subtype information to ensure that the most appropriate treatment regimen is selected. Most current genotyping methods are unable to detect mixed genotypes from two or more HCV infections. Next generation sequencing (NGS) allows for rapid and low cost mass sequencing of viral genomes and provides an opportunity to probe the viral population from a single host. In this paper, the possibility of using short NGS reads for direct HCV genotyping without genome assembly was evaluated. We surveyed the publicly-available genetic content of three HCV drug target regions (NS3, NS5A, NS5B) in terms of whether these genes contained genotype-specific regions that could predict genotype. Six genotypes and 38 subtypes were included in this study. An automated phylogenetic analysis based HCV genotyping method was implemented and used to assess different HCV target gene regions. Candidate regions of 250-bp each were found for all three genes that have enough genetic information to predict HCV genotypes/subtypes. Validation using public datasets shows 100% genotyping accuracy. To test whether these 250-bp regions were sufficient to identify mixed genotypes, we developed a random primer-based method to sequence HCV plasma samples containing mixtures of two HCV genotypes in different ratios. We were able to determine the genotypes without ambiguity and to quantify the ratio of the abundances of the mixed genotypes in the samples. These data provide a proof-of-concept that this random primed, NGS-based short-read genotyping approach does not need prior information about the viral population and is capable of detecting mixed viral infection.

  11. 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.

  12. A sensitive serodiagnosis of hepatitis C virus (HCV) infection with two non-fused peptides: comparison of antibody responses detected with a newly developed assay and a commercial second-generation test.

    Science.gov (United States)

    Sato, A; Ida, N; Ishikawa, M; Tanahashi, K; Nakamura, H; Sho, Y; Arima, T; Kunitomo, T

    1993-01-01

    An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of anti-HCV antibody. We assayed for antibodies against either oligopeptide (S29-1) deduced from the nucleocapsid gene or the product of nonstructural region (NS3) synthesized in a recombinant Escherichia coli (S4). To reduce false-positive results induced by non-specific binding of antibodies with a carrier protein and to increase the sensitivity of an immunoassay, non-fused S4 peptide was prepared by the recombinant DNA technique and site-specific proteolysis (by factor Xa). In 71 non-A, non-B hepatitis patients with chronic liver disease, 70 (98.5%) were positive by S29-1/S4 ELISA as well as by a second-generation test (Abbott II). On the other hand, of 40 serum samples from blood donors, in which anti-N14 (core) and C100-3 antibodies were not detected but hepatitis C virus (HCV) RNA was detectable by polymerase chain reaction (PCR), 24 (60%) were positive by S29-1/S4 ELISA, whereas only 18 (45%) were diagnosed by Abbott II. In addition, based on results in a small group of 92 blood donors, detection of anti-S29-1/S4 antibody correlated well with HCV viremia as confirmed by PCR. These results indicated that the preparation of nonfused protein (S4) by recombinant DNA technique and a combination of S29-1 and S4 as immobilized antigens in an ELISA provide a sensitive and specific diagnosis for HCV infection with good correlation with the presence of viral RNA as confirmed by PCR. PMID:7688847

  13. HCV and HBV coexist in HBsAg-negative patients with HCV viremia; possibility of coinfection in these patients must be considered in HBV-high endemic area

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong Soon [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1998-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers and is highly associated with HBV infection in Korea. It has been suggested that HCV core protein may impair the polymerase activity of HBV in vitro, potentially lowering HBV titre in coinfected patients. The aim of this study was to confirm the coexistence of HBV viremia in HCV infected patients HCC who have apparent HBsAg seronegativity. The serological profiles of HBV and HCV in 616 patients with HCC were analysed and coinfection rate of HBV and HCV investigated. Sera were obtained from 16 patients who were both anti-HCV and HCV RNA positive but HbsAg negative, and tested for HBV BY PCR. As a control group, sera were obtained from 15 patients with HCC and 30 non-A abd non-B chronic hepatitis patients without HCC; both were anti-HCV, HCV-RNA, and HBsAg negative and tested for HBV PCR. Of 616 patients with HCC, 450 (73.1 %) had current HBV infection, 48 (7.8 %) had anti-HCV antibodies, and nine (1.5 %) had viral markers of both HCV abd HBV by serological profiles. Of 27 the patients with HCV viremia and HBsAg seronegativity, 14 (51.9 %) showed HBV viremia by PCR. In contrast, of the 75 patients in the control group who were both HCV PCR negative and HBsAg negative, five (11.1 %) showed HBV viremia by PCR. The PCR for HBV revealed coexistent HBV viremia in HCV viremia patients, despite HBsAg negativity by EIA. In HBV-endemic areas, the possibility of coinfection of HBV in HBsAg-negative patients with HCV viremia should be considered and molecular analysis for HBV-DNA performed. (author). 18 refs., 4 tabs.

  14. 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

  15. Occult HCV infection: an unexpected finding in a population unselected for hepatic disease.

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    Laura De Marco

    Full Text Available BACKGROUND: Occult Hepatitis C virus (HCV infection is a new pathological entity characterized by presence of liver disease and absence or very low levels of detectable HCV-RNA in serum. Abnormal values of liver enzymes and presence of replicative HCV-RNA in peripheral blood mononuclear cells are also observed. Aim of the study was to evaluate occult HCV occurrence in a population unselected for hepatic disease. METHODOLOGY/PRINCIPAL FINDINGS: We chose from previous epidemiological studies three series of subjects (n = 276, age range 40-65 years unselected for hepatic disease. These subjects were tested for the presence of HCV antibodies and HCV-RNA in plasma and in the peripheral blood mononuclear cells (PBMCs by using commercial systems. All subjects tested negative for HCV antibodies and plasma HCV-RNA and showed normal levels of liver enzymes; 9/276 patients (3.3% were positive for HCV-RNA in PBMCs, identifying a subset of subjects with potential occult HCV infection. We could determine the HCV type for 8 of the 9 patients finding type 1a (3 patients, type 1b (2 patients, and type 2a (3 patients. CONCLUSIONS: The results of this study show evidence that occult HCV infection may occur in a population unselected for hepatic disease. A potential risk of HCV infection spread by subjects harbouring occult HCV infection should be considered. Design of prospective studies focusing on the frequency of infection in the general population and on the clinical evolution of occult HCV infection will be needed to verify this unexpected finding.

  16. 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.

  17. 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.

  18. HCV -RNA 与 HCV -Ab、ALT、TP 相关性研究%The Relativity Analysis of HCV-RNA, HCV-Ab, ALT and TP from Hepatitis C Patients

    Institute of Scientific and Technical Information of China (English)

    李昕; 管世鹤

    2015-01-01

    探讨丙型肝炎患者体内 HCV -RNA、HCV -Ab、ALT 和 TP 间的相互关系。采用ELISA检测708例HCV-Ab阳性的丙型肝炎疑似患者,以RT-PCR检测血清HCV-RNA载量,全自动生化仪定量检测ALT和TP。 HCV-Ab表达水平与HCV-RNA载量有关,HCV-RNA载量与ALT异常率呈正相关性,但HCV-RNA载量与ALT含量无相关性,与TP含量亦无相关性。708例HCV-Ab阳性患者中男性多于女性,差异无统计学意义( P>0.05);40岁以上患者比例多于40岁以下患者比例,差异有统计学意义( P<0.05)。 HCV-RNA与HCV-Ab、ALT具有一定相关性,丙型肝炎以40岁以上男性患者多见,应引起临床重视。%In order to investigate the relativity among HCV -RNA, HCV-Ab, ALT and TP in hepatitis C pa-tients, 708 suspected hepatitis C patients with HCV -Ab positive were checked by using the ELISA method , with real-time detecting HCV-RNA in those bloods by Fluorescentrt -PCR, ALT and TP detected by automat-ic biochemical analyzer .The test results showed that HCV -Ab expression level is related with HCV -RNA con-tent.HCV-RNA content is positively correlated with abnormal rate of ALT .But HCV-RNA content is not cor-related with ALT content and TP content .Among the 708 patients, the HCV-Ab positive percentage of men is more than women , and there is no statistically significant difference ( P>0 .05 );the ratio of the ≥40 years old patients is greater than <40 years old patients, and the difference is statistically significant (P<0.05).HCV-RNA, HCV-Ab and ALT have certain relativity .Among hepatitis C patients men of over 40 years old are more , and should be paid more clinical attention .

  19. 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.

  20. 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.

  1. 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

  2. Prevalence, genotypes and factors associated with HCV infection among prisoners in Northeastern Brazil

    Institute of Scientific and Technical Information of China (English)

    Bruno Fernandes de Oliveira Santos; Nathalie Oliveira de Santana; Alex Vianey Callado Franca

    2011-01-01

    AIM: To determine hepatitis C virus (HCV) seroprevalence and its genotypes, and to identify the factors associated with HCV infection. METHODS: This cross-sectional study, conducted in two prisons (one male and one female) in the State of Sergipe, Brazil, comprised 422 subjects. All of the prisoners underwent a rapid test for the detection of HCV antibodies. Patients with a positive result were tested for anti- HCV by enzyme linked immunosorbent assay and for HCV RNA by qualitative polymerase chain reaction (PCR). The virus genotype was defined in every serum sample that presented positive for PCR-HCV. In order to determine the factors independently associated with positive serology for HCV, multivariate logistic regression was used. RESULTS: HCV seroprevalence was 3.1%. Of the 13 subjects with positive anti-HCV, 11 had viremia confirmed by PCR. Of these, 90.9% had genotype 1. A total of 43 (10.2%) were injecting drug users, and HCV seroprevalence in this subgroup was 20.6%. The variable most strongly associated with positive serology for HCV was use of injecting drugs [odds ratio (OR), 23.3; 95% confidence interval (CI), 6.0-90.8]. Age over 30 years (OR, 5.5; 95%CI, 1.1-29.2), history of syphilis (OR, 9.8; 95%CI, 1.7-55.2) and history of household contact with HCV positive individual (OR, 14.1; 95%CI, 2.3-85.4) were also independently associated with HCV infection. CONCLUSION: Most of the HCV transmissions result from parenteral exposure. However, there is evidence to suggest a role for sex and household contact with an infected subject in virus transmission.

  3. 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

  4. 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...

  5. Analysis of HBsAg/NAT test results in Shenzhen city in 2003-2012%深圳地区2003~2012年间无偿献血者抗-HCV 抗体与核酸检出情况分析∗

    Institute of Scientific and Technical Information of China (English)

    熊姣梅; 吴桂丹; 郑欣; 杨爱莲; 魏天莉

    2015-01-01

    目的:调查分析深圳地区2003~2013年献血者抗-丙型肝炎病毒(HCV)抗体/病毒核酸检测(NAT)阳性检出情况。方法献血者经乙型肝炎病毒表面抗原(HBsAg)、丙氨酸氨基转移酶(ALT)快速试纸条初筛后,使用进口与国产两种酶联免疫吸附试验(ELISA)及血液病毒 NAT 方法检测抗-HCV 抗体、HCV RNA,对11年来献血者抗-HCV 抗体、NAT 阳性率流行趋势进行统计分析比较。结果深圳地区2003~2013年献血人数逐年增长,抗-HCV 抗体阳性率呈 M 型检出走势,于2013年达到最低。献血者抗-HCV 抗体阳性/NAT 阴性检出率与抗-HCV 抗体走势一致,而真实感染 HCV 的指标抗-HCV 抗体与 NAT 双阳性组检出率则缓慢下降;对抗-HCV 抗体阳性献血者在不同分类组别比较发现,31~45岁献血者组、初次献血者组的抗-HCV 抗体检出率分别高于其他年龄组与重复献血者(P <0.05);抗-HCV 抗体阴性/NAT 阳性献血者有3例(检出率为1/134518)。结论NAT 检测为常规酶联免疫方法的补充检测手段,缺一不可,能大大降低输血风险,而 NAT 阴性献血者的抗-HCV 抗体阳性占多数的检测结果应引起重视,避免因假阳性导致此类献血者资格淘汰。%Objective To investigate and analyze the popular trend of HBV infection in blood donors in Shenzhen City from 2003 to 2012.Methods After preliminary routine strip screening of HBsAg、ALT,blood samples were tested by using both domestic and imported ELISA reagents along with nucleic acid detection,then tried to find a trend of HCV prevalence in blood donor by analysis data.Results Blood donors′number rised year by year from 2003 to 2013,but prevalence of anti-HCV gave a volatile reception, which had a lowest rate at 2013.The detection rate of anti-HCV positive/NAT-was basically the same as anti-HCV positive,where-as the detection rate of anti-HCV positive/NAT positive declined slightly in those confirmed HCV infectors;blood donors were

  6. 丙肝患者HCV-Ab、HCV-RNA、HCV-Ag试剂盒联合检测体会

    Institute of Scientific and Technical Information of China (English)

    王沈莉

    2014-01-01

    目的 探讨HCV-Ab、HCV-RNA、HCV-Ag联合检测的意义.方法 用丙型肝炎抗体(HCV-Ab)、丙型肝炎病毒核酸(HCV-RNA)扩增(RNA)荧光定量及丙型肝核心抗原(HCV-Ag) 三种试剂盒分别检测血清中的HCV-Ab、HCV-RNA、HCV-Ag三种标志物.结果 根据丙型肝炎病毒在体内存在的时间,通过90例疑似丙型肝炎患者血清检测,HCV-Ab 87人阳性,HCV-RNA 67人阳性,HCV-Ag 55人阳性.结论 HCV-Ab、HCV-RNA、HCV-Ag联合检测有助于临床诊断、用药及疗效观察.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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...

  12. 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...

  13. 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

  14. 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.

  15. Identification and Linkage to Care of HCV-Infected Persons in Five Health Centers - Philadelphia, Pennsylvania, 2012-2014.

    Science.gov (United States)

    Coyle, Catelyn; Viner, Kendra; Hughes, Elizabeth; Kwakwa, Helena; Zibbell, Jon E; Vellozzi, Claudia; Holtzman, Deborah

    2015-05-01

    Approximately three million persons in the United States are infected with hepatitis C virus (HCV), a blood-borne pathogen that is an increasing cause of liver disease and mortality in the United States. Treatments for HCV are curative, of short duration, and have few associated side effects, increasing the importance of identifying HCV-infected persons. Many persons with HCV infection were infected decades ago, before implementation of prevention measures and most are unaware of their infection, regardless of when it occurred. Most newly diagnosed cases are associated with injection drug use. Persons born during 1945-1965 have a fivefold higher risk of HCV infection than other adults and the highest risk for HCV-related morbidity and mortality. CDC recommends testing for this group, for persons who inject drugs, and others at risk for HCV infection. From October 2012 through July 2014, the National Nursing Centers Consortium (NNCC) carried out a project to integrate routine HCV testing and linkage-to-care in five federally qualified health centers in Philadelphia, PA, that primarily serve homeless persons and public housing residents. During the project period, 4,514 patients across the five centers were tested for HCV. Of these, 595 (13.2%) were HCV-antibody positive and 550 (92.4%) had a confirmatory HCV-RNA test performed. Of those who had a confirmatory HCV-RNA test performed, 390 (70.9%) were identified as having current (i.e., chronic) HCV infection (overall prevalence = 8.6%). Of those currently infected with HCV, 90% were informed of their status, 78% were referred to an HCV care specialist, and 62% went to the referred specialist for care. Replicable system modifications that improved HCV testing and care included enhancements to electronic medical records (EMRs), simplification of HCV testing protocols, and addition of a linkage-to-care coordinator. Findings from this project highlight the need for innovative strategies for HCV testing, care, and

  16. 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 HCV......-RNA positive. Among the HCV-RNA positive recipients symptoms were present in 38% (25/66 reported), elevated ALT was found in 53% (41/77 tested) and cirrhosis was found in 11% (6/54 biopsied). Treatment with interferon-alpha was initiated in 23 patients, corresponding to 26% of HCV-RNA positive recipients...

  17. Interferon Response in Hepatitis C Virus (HCV) Infection: Lessons from Cell Culture Systems of HCV Infection.

    Science.gov (United States)

    Sung, Pil Soo; Shin, Eui-Cheol; Yoon, Seung Kew

    2015-01-01

    Hepatitis C virus (HCV) is a positive-stranded RNA virus that infects approximately 130-170 million people worldwide. In 2005, the first HCV infection system in cell culture was established using clone JFH-1, which was isolated from a Japanese patient with fulminant HCV infection. JFH-1 replicates efficiently in hepatoma cells and infectious virion particles are released into the culture supernatant. The development of cell culture-derived HCV (HCVcc) systems has allowed us to understand how hosts respond to HCV infection and how HCV evades host responses. Although the mechanisms underlying the different outcomes of HCV infection are not fully understood, innate immune responses seem to have a critical impact on the outcome of HCV infection, as demonstrated by the prognostic value of IFN-λ gene polymorphisms among patients with chronic HCV infection. Herein, we review recent research on interferon response in HCV infection, particularly studies using HCVcc infection systems.

  18. Analysis of HCV genotypes from blood donors shows three new HCV type 6 subgroups exist in Myanmar.

    Directory of Open Access Journals (Sweden)

    Shinji T

    2004-06-01

    Full Text Available The prevalence of hepatitis C virus (HCV genotypes in Myanmar in comparison with the rest of Southeast Asia is not well known. Serum samples were obtained from 201 HCV antibody-positive volunteer blood donors in and around the Myanmar city of Yangon. Of these, the antibody titers of 101 samples were checked by serial dilution using HCV antibody PA test II and Terasaki microplate as a low-cost method. To compare antibody titers by this method and RNA identification, we also checked HCV-RNA using the Amplicor 2.0 test. Most high-titer groups were positive for HCV-RNA. Of the 201 samples, 110 were successfully polymerase chain reaction (PCR amplified. Among them, 35 (31.8% were of genotype 1, 52 (47.3% were of genotype 3, and 23 (20.9% were of type 6 variants, and phylogenetic analysis of these type 6 variants revealed that 3 new type 6 subgroups exist in Myanmar. We named the subgroups M6-1, M6-2, and M6-3. M6-1 and M6-2 were relatively close to types 8 and 9, respectively. M6-3, though only found in one sample, was a brand-new subgroup. These subtypes were not seen in Vietnam, where type 6 group variants are widely spread. These findings may be useful for analyzing how and when these subgroups were formed.

  19. Prevalence and coexistence of diabetes in HIV, HCV and HIV/HCV co- infection in Kermanshah -Iran

    Directory of Open Access Journals (Sweden)

    Alireza Janbakhsh

    2012-01-01

    Full Text Available Background: Beside various factors for producing diabetes, it seems that chronic hepatitis C, HIV/HCV co-infection, and anti-retroviral treatment especially including protease inhibitors may predispose to diabetes. This study conducted to determine prevalence of diabetes in HIV and HCV patients.Methods: The registries of 150 HCV patients, 50 HIV patients and 90 HIV/HCV co-infected patients in Hepatic Clinics and consulting center for behavioral disorders in Kermanshah Western Iran was studied. The patients selected using convenience sampling method. Variables including age, sex, duration of disease, injecting drug usage, liver enzymes level, CD4 count, treatment with anti retroviral, treatment with interferon and blood sugar level were collected. Subjects with FBS≥126 or BS≥200 mg/dl described as diabetic. Data analyzed using chi-square and Fisher tests and SPSS software.Results: The prevalence of diabetes was 2.7%, 4% and 2.2% among patients infected with HCV, HIV and HIV/HCV co infection respectively. None of the variables such as age, sex, liver enzymes, injecting drug usage, CD4 count, antiretroviral treatment and interferon determined as risk factors for diabetes.Conclusion: Our finding showed that hepatitis C is not a definitive risk factor for diabetes. Although prevalence of diabetes in these patients was determined lower than general Kermanshah population, but factors such as difference in mean age and body mass index (BMI may contribute in diabetes incidence. Infection with HIV and co-infection with HIV/HCV and treatment with anti retroviral drugs were not risk factors for diabetes.

  20. Primary screening of blood donors by nat testing for HCV-RNA: development of an "in-house" method and results Triagem primária de doadores de sangue por teste de ácidos nucléicos: desenvolvimento de um método não-comercial e resultados

    Directory of Open Access Journals (Sweden)

    Silvano Wendel

    2007-06-01

    Full Text Available An "in-house" RT-PCR method was developed that allows the simultaneous detection of the RNA of the Hepatitis C Virus (HCV and an artificial RNA employed as an external control. Samples were analyzed in pools of 6-12 donations, each donation included in two pools, one horizontal and one vertical, permitting the immediate identification of a reactive donation, obviating the need for pool dismembering. The whole process took 6-8 hours per day and results were issued in parallel to serology. The method was shown to detect all six HCV genotypes and a sensitivity of 500 IU/mL was achieved (95% hit rate. Until July 2005, 139,678 donations were tested and 315 (0.23% were found reactive for HCV-RNA. Except for five false-positives, all 310 presented the corresponding antibody as well, so the yield of NAT-only donations was zero, presenting a specificity of 99.83%. Detection of a window period donation, in the population studied, will probably demand testing of a larger number of donations. International experience is showing a rate of 1:200,000 - 1:500,000 of isolated HCV-RNA reactive donations.Desenvolveu-se uma metodologia própria ("in-house" baseada em RT-PCR, que permite detectar simultaneamente o RNA do vírus HCV e de um RNA artificial empregado como controle externo. As amostras são analisadas em pools de 6-12 doações, cada doação sendo incluída em dois pools diferentes, um horizontal e um vertical, permitindo a identificação imediata de uma doação reativa, sem a necessidade de desmembrar-se um pool reativo. O processo todo consumiu de 6-8 horas diárias e os resultados foram emitidos em paralelo à sorologia. O método detectou os seis genótipos de HCV, com um limite de sensibilidade de 500 UI/mL (95% hit rate. Até julho de 2005 haviam sido testadas 139.678 doações com a detecção de 315 (0,23% doações reativas para HCV-RNA. Exceto cinco falso-positivas, todas estas doações também apresentavam o respectivo anticorpo, portanto

  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. Incidence of hepatitis C virus (HCV in a multicenter cohort of HIV-positive patients in Spain 2004-2011: increasing rates of HCV diagnosis but not of HCV seroconversions.

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    Paz Sobrino-Vegas

    Full Text Available OBJECTIVES: We aim to describe rates and risk factors of Hepatitis C Virus (HCV diagnoses, follow-up HCV testing and HCV seroconversion from 2004-2011 in a cohort of HIV-positive persons in Spain. METHODS: CoRIS is a multicentre, open and prospective cohort recruiting adult HIV-positive patients naïve to antiretroviral therapy. We analysed patients with at least one negative and one follow-up HCV serology. Incidence Rates (IR were calculated and multivariate Poisson regression was used to estimate adjusted Rates Ratios (aIRR. RESULTS: Of 2112 subjects, 53 HCV diagnoses were observed, IR = 0.93/100 py (95%CI: 0.7-1.2. IR increased from 0.88 in 2004-05 to 1.36 in 2010-11 (aIRR = 1.55; 95%CI: 0.37-6.55. In men who have sex with men (MSM from 0.76 to 1.10 (aIRR = 1.45; 95%CI: 0.31-6.82; in heterosexual (HTX subjects from 1.19 to 1.28 (aIRR = 1.08; 95%CI: 0.11-10.24. HCV seroconversion rates decreased from 1.77 to 0.65 (aIRR = 0.37; 95%CI: 0.12-1.11; in MSM from 1.06 to 0.49 (aIRR = 0.46; 95%CI: 0.09-2.31; in HTX from 2.55 to 0.59 (aIRR = 0.23; 95%CI: 0.06-0.98. HCV infection risk was higher for injecting drug users (IDU compared to HTX (aIRR = 9.63;95%CI: 2.9-32.2; among MSM, for subjects aged 40-50 compared to 30 or less (IRR = 3.21; 95%CI: 1.7-6.2; and among HTX, for female sex (aIRR = 2.35; 95%CI: 1.03-5.34 and <200 CD4-count (aIRR = 2.39; 95%CI: 0.83-6.89. CONCLUSION: We report increases in HCV diagnoses rates which seem secondary to intensification of HCV follow-up testing but not to rises in HCV infection rates. HCV IR is higher in IDU. In MSM, HCV IR increases with age. Among HTX, HCV IR is higher in women and in subjects with impaired immunological situation.

  3. Direct anti-HCV agents

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    Xingquan Zhang

    2016-01-01

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

  4. Animal models for HCV and HBV studies

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    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

  5. HBV-DNA in hemodialysis patients infected by HCV

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    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.

  6. Self-Reported HIV and HCV Screening Rates and Serostatus Among Substance Abuse Treatment Patients.

    Science.gov (United States)

    Hernández, Diana; Feaster, Daniel J; Gooden, Lauren; Douaihy, Antoine; Mandler, Raul; Erickson, Sarah J; Kyle, Tiffany; Haynes, Louise; Schwartz, Robert; Das, Moupali; Metsch, Lisa

    2016-01-01

    Substance users are at increased risk for HIV and HCV infection. Still, many substance use treatment programs (SUTP) fail to offer HIV/HCV testing. The present secondary analysis of screening data from a multi-site randomized trial of rapid HIV testing examines self-reported HIV/HCV testing patterns and serostatus of 2473 SUTP patients in 12 community-based sites that had not previously offered on-site testing. Results indicate that most respondents screened for the randomized trial tested more than a year prior to intake for HIV (52 %) and HCV (38 %). Prevalence rates were 3.6 and 30 % for HIV and HCV, respectively. The majority of participants that were HIV (52.2 %) and HCV-positive (40.5 %) reported having been diagnosed within the last 1-5 years. Multivariable logistic regression showed that members of high-risk groups were more likely to have tested. Bundled HIV/HCV testing and linkage to care issues are recommended for expanding testing in community-based SUTP settings.

  7. 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

  8. 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

  9. IL28B Polymorphism Is Not Associated With HCV Protease Diversity in Patients Co-Infected With HIV and HCV Treated With Pegylated Interferon and Ribavirin

    Science.gov (United States)

    Osinusi, Anu; Chary, Aarthi; Winters, Mark A.; Naggie, Susanna; Masur, Henry; Polis, Michael A.; Kottilil, Shyam; Holodniy, Mark

    2013-01-01

    Recent studies have demonstrated that IL28B polymorphisms predict therapeutic responses in chronic hepatitis C virus (HCV)-treated patients; however, the effect on HCV viral diversity, particularly on the HCV protease gene, is not clear. This study sought to evaluate the effect of IL28B polymorphisms on HCV diversity at NS3/4 protease region, which may influence therapeutic response to an HCV protease inhibitor based regimen. Twenty-two patients co-infected with HIV and HCV genotype 1, treatment-naïve on stable HIV antiretroviral therapy initiating interferon-based treatment were evaluated. Plasma HCV NS3 gene diversity was analyzed by clonal analysis at baseline and end of treatment. IL28B (rs12979860) genotypes were tested for associations with virologic outcomes and diversity parameters. There was similar baseline NS3 diversity in patients with CC (favorable) genotype compared to those with CT/TT (unfavorable) genotypes. There was no significant association between IL28B genotype and baseline NS3 nucleotide p-distance, dS-dN, amino acid p-distance, or nucleotide changes. Among patients without a sustained virologic response, between baseline and follow-up there was a significant trend towards decreased diversity after treatment among patients with favorable genotype, which was not observed in unfavorable genotypes. In patients treated with peginterferon/ribavirin therapy, IL28B polymorphism was not associated with enhanced NS3 diversity at baseline. Among non-SVR patients with the less favorable genotype, there was no change in diversity after treatment. This suggests that IL28B genotype is unlikely to have a negative impact on subsequent HCV PI efficacy in patients co-infected with HIV and HCV patients who have previously failed HCV therapy. PMID:22930497

  10. HCV Infection and B-Cell Lymphomagenesis

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    Masahiko Ito

    2011-01-01

    Full Text Available Hepatitis C virus (HCV has been recognized as a major cause of chronic liver diseases worldwide. It has been suggested that HCV infects not only hepatocytes but also mononuclear lymphocytes including B cells that express the CD81 molecule, a putative HCV receptor. HCV infection of B cells is the likely cause of B-cell dysregulation disorders such as mixed cryoglobulinemia, rheumatoid factor production, and B-cell lymphoproliferative disorders that may evolve into non-Hodgkin's lymphoma (NHL. Epidemiological data indicate an association between HCV chronic infection and the occurrence of B-cell NHL, suggesting that chronic HCV infection is associated at least in part with B-cell lymphomagenesis. In this paper, we aim to provide an overview of recent literature, including our own, to elucidate a possible role of HCV chronic infection in B-cell lymphomagenesis.

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

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    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

  12. 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)

  13. HCV-RNA与HCV-cAg检测的相关性分析%Study on correlation analysis on serum HCV-RNA and HCV-cAg

    Institute of Scientific and Technical Information of China (English)

    苏明权; 杨柳; 王娟; 常亮; 肖凤静; 马越云; 郝晓柯

    2013-01-01

    目的 探讨丙型肝炎病毒核心抗原(HCV-cAg)与HCV-RNA检测的相关性及其在丙型肝炎病毒感染诊断中的价值.方法 采用双抗体夹心酶联免疫分析法(ELISA)检测HCV-cAg;采用实时荧光定量PCR法检测HCV-RNA,以了解两者检测方法的相关性.结果 在160例HCV-RNA阳性血清中,HCV-cAg阳性148例,阳性符合率92.5%;在60例HCV-cAg阳性血清中,HCV-RNA阳性59例,阳性符合率98.3%.结论 通过对HCV-RNA与HCV-cAg检测,说明HCV核心抗原与HCV-RNA检测可作为反映HCV复制的间接指标,预防窗口期感染.由于HCV-cAg在方法学上与HCV-RNA相比,具有方法简便、快速、价廉,所需设备简单,易于普及应用等优点,特别是在不具备HCV-RNA检测条件的基层医疗单位作为HCV感染检测的直接证据具有重要的意义.

  14. International epidemiological studies on HIV, HCV and STI

    NARCIS (Netherlands)

    J.J. van der Helm

    2014-01-01

    This thesis comprises international epidemiological studies on HIV, Hepatitis C (HCV) and sexually transmitted infections (STI) and the evaluation of STI diagnostic tests with the ultimate goal to decrease spread and disease burden of these infections. The main conclusions are: 1. Without the use of

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

    Science.gov (United States)

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

    2006-02-01

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

  16. 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.

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

    Science.gov (United States)

    MacParland, Sonya A.; Fadel, Saleh M.; Mihajlovic, Vesna; Fawaz, Ali; Kim, Connie; Rahman, A. K. M. Nur-ur; Liu, Jun; Kaul, Rupert; Kovacs, Colin; Grebely, Jason; Dore, Gregory J.; Wong, David K.; Ostrowski, Mario A.

    2016-01-01

    Background Decreased hepatitis C virus (HCV) clearance, faster cirrhosis progression and higher HCV RNA levels are associated with Human Immunodeficiency virus (HIV) coinfection. The CD4+ T helper cytokines interleukin (IL)-21 and IL-17A are associated with virus control and inflammation, respectively, both important in HCV and HIV disease progression. Here, we examined how antigen-specific production of these cytokines during HCV mono and HIV/HCV coinfection was associated with HCV virus control. Methods We measured HCV-specific IL-21 and IL-17A production by transwell cytokine secretion assay in PBMCs from monoinfected and coinfected individuals. Viral control was determined by plasma HCV RNA levels. Results In acutely infected individuals, those able to establish transient/complete HCV viral control tended to have stronger HCV-specific IL-21-production than non-controllers. HCV-specific IL-21 production also correlated with HCV viral decline in acute infection. Significantly stronger HCV-specific IL-21 production was detected in HAART-treated coinfected individuals. HCV-specific IL-17A production was not associated with lower plasma HCV RNA levels in acute or chronic HCV infection and responses were stronger in HIV coinfection. HCV-specific IL-21/ IL-17A responses did not correlate with microbial translocation or fibrosis. Exogenous IL-21 treatment of HCV-specific CD8+ T cells from monoinfected individuals enhanced their function although CD8+ T cells from coinfected individuals were somewhat refractory to the effects of IL-21. Conclusions These data show that HCV-specific IL-21 and IL-17A-producing T cells are induced in HIV/HCV coinfection. In early HIV/HCV coinfection, IL-21 may contribute to viral control, and may represent a novel tool to enhance acute HCV clearance in HIV/HCV coinfected individuals. PMID:27124305

  18. Pyridine hydroxamic acids are specific anti-HCV agents affecting HDAC6.

    Science.gov (United States)

    Kozlov, Maxim V; Kleymenova, Alla A; Romanova, Lyudmila I; Konduktorov, Konstantin A; Kamarova, Kamila A; Smirnova, Olga A; Prassolov, Vladimir S; Kochetkov, Sergey N

    2015-06-01

    Recently we reported benzohydroxamic acids (BHAs) as potent and selective inhibitors of hepatitis C virus (HCV) replicon propagation. In this work 12 pyridine hydroxamic acids (PHAs) were synthesized and tested in full-genome replicon assay. It was found that PHAs possessed very similar anti-HCV properties compared to BHAs. Both classes of hydroxamic acids caused hyperacetylation of α-tubulin pointing to inhibition of histone deacetylase 6 (HDAC6) as part of their antiviral activity. The tested compounds did not inhibit the growth of poliovirus, displaying high selectivity against HCV.

  19. 男性HIV和HCV并发感染者HCV抗体的表达%Study on the HCV Antibody Response in Men HIV and HCV Concurrent Infections

    Institute of Scientific and Technical Information of China (English)

    贺美荣; 焦东丽; 贾艳春; 严震

    2012-01-01

    目的 观察人免疫缺陷病毒(HIV)男性患者并发丙型肝炎病毒(HCV)感染后HCV抗体的表达情况,探讨影响HCV抗体表达的因素.方法 选取经筛选检测最终确诊的HIV/HCV并发感染男性患者23例,每隔3个月随访一次共随访6个月.检测HIV及HCV病毒载量、CD4+T细胞计数及HCV抗体.结果 首次HCV RNA检测阳性时78.3%的患者HCV抗体阴性;3个月后,34.8%的患者为HCV抗体阴性;6个月后,17.4%的患者HCV抗体为阴性.结论 HIV 并发HCV的男性感染者,HCV抗体阳性率表达较低,应早期联合核酸检测.%Objective To estimated the positive rates of antibodies and the influencing factors of antibodies expansion in Human immunoddficiency virus(HIV) men infected with hepatitis C virus(HCV). Methods 23 HIV-positive patients with early HCV infection were identified. Plasma samples obtained at 3 monthly intervals( total 6 month) for routine monitoring of HIV and HCV viral load,CD4 cell counts,HCV antibodies. Results On first amplification of HCV,78. 3% of patients were serologically negative. Antibody detection remain seronegative 34. 8% by 3 months to 17. 4% at 6 months. Conclusion The lower of HCV antibodies positive rates in HIV men with HCV should early combination of nucleic acid testing.

  20. 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

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

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    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

  2. 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...

  3. 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

  4. 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.

  5. Complementary role of HCV and HIV in T-cell activation and exhaustion in HIV/HCV coinfection

    NARCIS (Netherlands)

    Feuth, T.; Arends, J.E.; Fransen, J.H.; Nanlohy, N.M.; Erpecum, K.J. van; Siersema, P.D.; Hoepelman, A.I.; Baarle, D. van

    2013-01-01

    OBJECTIVES: To investigate whether T-cell activation and exhaustion is linked to HCV- and HIV disease parameters in HIV/HCV infected individuals, we studied T-cell characteristics in HIV/HCV coinfected patients and controls. METHODS: 14 HIV/HCV coinfected, 19 HCV monoinfected, 10 HIV monoinfected pa

  6. Inhibition of HCV 3a genotype entry through Host CD81 and HCV E2 antibodies

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    Ashfaq Usman A

    2011-11-01

    Full Text Available Abstract Background HCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage hepatocellular carcinoma and death. HCV glycoproteins play an important role in HCV entry by binding with CD81 receptors. Hence inhibition of virus at entry step is an important target to identify antiviral drugs against HCV. Methods and result The present study elaborated the role of CD81 and HCV glycoprotein E2 in HCV entry using retroviral pseudo-particles of 3a local genotype. Our results demonstrated that HCV specific antibody E2 and host antibody CD81 showed dose- dependent inhibition of HCV entry. HCV E2 antibody showed 50% reduction at a concentration of 1.5 ± 1 μg while CD81 exhibited 50% reduction at a concentration of 0.8 ± 1 μg. In addition, data obtained with HCVpp were also confirmed with the infection of whole virus of HCV genotype 3a in liver cells. Conclusion Our data suggest that HCV specific E2 and host CD81 antibodies reduce HCVpp entry and full length viral particle and combination of host and HCV specific antibodies showed synergistic effect in reducing the viral titer.

  7. Community-based survey of HCV and HIV coinfection in injection drug abusers in Sichuan Province of China

    Institute of Scientific and Technical Information of China (English)

    Yu-Hua Ruan; Yi-Ming Shao; Kun-Xue Hong; Shi-Zhu Liu; Yi-Xin He; Feng Zhou; Guan-Ming Qin; Kang-Lin Chen; Hui Xing; Jian-Ping Chen

    2004-01-01

    AIM: To investigate the prevalence and risk factors of HCV/HIV coinfection in injection drug abusers (IDAs) in Lianshan Yi Autonomous Prefecture of Sichuan province, China.METHODS: From November 8, 2002 to November 29, 2002,a community-based survey was conducted to investigate the demographic characteristics, patterns of shared injectors devices and sexual behaviors in IDAs. Blood samples were also collected to test HCV and HIV infection. A total of 379subjects were recruited in the study through community outreach and peer recruiting methods.RESULTS: Of the 379 IDAs, the HCV prevalence and HIV prevalence were 71.0% and 11.3%, respectively, and HCV/HIV coinfection was 11.3%. HCV infection was found in 100% and 67.3% of HIV-positive and HIV-negative IDAs,respectively. HIV prevalence was 16.0% in HCV positive IDAs while none of the HCV negative IDAs was positive for HIV. Ethnicity, shared needles or syringes and cotton in the past 3 mo and syphilis infection were associated with HCV/HIV coinfection shown by univariate analysis using chi-square test. Multivariate logistic regression analysis showed that shared needles or syringes in the past 3 mo (Odds ratio=3.121, 95% CI: 1.278-7.617, P<0.05) and syphilis infection (Odds ratio=2.914, 95% CI: 1.327-6.398,P<0.01) were significantly associated with HCV infection.No statistically significant association was found in univariate analysis between sexual behaviors and HCV/HIV coinfection.CONCLUSION: Shared needles and syringes in the past 3 mo and syphilis infection were significantly associated with HCV infection. Further sero-epidemiological prospective cohort studies should be conducted to clarify the impact of syphilis and high risk sexual behaviors on HCV transmission through unprotected sexual intercourse.

  8. Reliability of immunoassays for anti-HCV antibodies (ELISA and RIBA II) in patients with essential mixed cryoglobulinemia (EMC).

    Science.gov (United States)

    Monteverde, A; Airoldi, G; Ballarè, M; Fortina, G; Quaglia, V; Pigatto, A; Manzini, P

    1993-01-01

    The recent reports of a very high frequency of signs of hepatitis C virus (HCV) infection among patients with essential mixed cryoglobulins (EMC) suggest new hypotheses for the pathogenesis of this disease. However, most of these studies have been seriously criticized. The serologic test designed for detection of anti-HCV antibodies (ELISA, RIBA I and II) may yield a significant rate of false-positive results when performed on cryoglobulinemic sera, and the detection of the HCV genome by PCR is still heavily conditioned by practical problems. Indirect, but possibly more reliable, evidence of HCV infection in cryoglobulinemic patients might come from the demonstration of anti-HCV antibodies by a conventional technique (ELISA or RIBA) in the purified polyclonal non-rheumatoid immunoglobulinemic fraction excreted in the urine by glomerular filtration. Fifty-two patients whose serum had tested positive for HCV antibodies (by ELISA and RIBA) on multiple occasions were enrolled in this study. They were diagnosed as having either EMC or HCV chronic hepatitis without cryoglobulinemia at least one year ago. The urine samples of these patients were tested for anti-HCV antibodies by ELISA and RIBA. In patients with chronic C hepatitis the antibodies most frequently found in the serum were anti-C33c and anti-C22-3. The results of the RIBA were substantially confirmed by ELISA, with a positive test in the urine of 30 of 32 seropositive patients. Similar results were obtained in patients with EMC II. We conclude that the specificity of the RIBA and ELISA tests for HCV antibodies in patients with EMC appears to be as high as in HCV+ patients without serum cryoglobulins. EMC patients have a high incidence of HCV infection and active chronic liver disease. PMID:7507807

  9. 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.

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

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    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

  11. The history of hepatitis C virus (HCV)

    DEFF Research Database (Denmark)

    Bukh, Jens

    2016-01-01

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

  12. [Pulmonary vasculitis as a clinical mask of HCV infection: efficiency of interferon-free antiviral therapy].

    Science.gov (United States)

    Stelmakh, V V; Kozlov, V K; Sukhanov, D S; Skipsky, I M

    2014-01-01

    The paper describes a clinical case of pulmonary vasculitis caused by hepatitis C virus (HCV). Its diagnosis was established on the basis of in-depth laboratory testing and an investigation of the molecular biological markers of viremia (polymerase chain reaction--PCR--HCV RNA) in peripheral blood mononuclear cells. By taking into account of extrahepatic HCV replication and contraindications to interferon therapy, the female patient was given an interferon-free antiviral therapy cycle using an interferonogenic inductor in combination with ribavirin. Pathogenic therapy (methylpred and ursodeoxycholic acid) was additionally performed. An interferon-free regimen of cycloferon + ribavirin led to sustained remission of HCV infection running with its systemic manifestations. The therapy could improve the function of not only the liver, but also the lung. In suspected extrahepatic HCV infections, an investigation of molecular biological markers for viremia (HCV RNA PCR) in the peripheral blood mononuclear cells is an essential diagnostic technique. Interferonogenic inductors, cycloferon in particular, should be used in combination with ribavirin when a chronic hepatitis C patient with the extrahepatic manifestations of HCV infection has contraindications to conventional therapy with recombinant interferon-α. PMID:25715495

  13. 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

  14. 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)

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...

  16. 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.

  17. 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

  18. Apoptosis and clinical severity in patients with psoriasis and HCV infection

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    Sami A Gabr

    2014-01-01

    Full Text Available Background: It has been proposed that hepatitis C virus (HCV antigens are involved in the pathogenesis of psoriasis and may contribute to severity of the disease. Increased expression of the apoptosis-regulating proteins p53 and tTG and decreased levels of bcl-2 in the keratinocytes of the skin of psoriatic patients have been reported. Aim: This study aims to identify the serum levels of apoptosis-regulating proteins in patients with psoriasis and without HCV infection and to study the relation between clinical severity of psoriasis and the presence of HCV infection. Materials and Methods: Disease severity was assessed by psoriasis area severity index score (PASI of 90 patients with psoriasis grouped as mild (n = 30, moderate (n = 30 and severe (n = 30; 20 healthy individuals were used as controls. All groups were subjected for complete history taking, clinical examination, and tests for liver function and HCV infection. The serum levels of apoptosis related proteins: p53, tTG and bcl-2 were estimated by enzyme linked immune sorbent assay (ELISA. Results: There was a statistically significant (P < 0.001 correlation between clinical severity of psoriasis and presence of HCV antibodies and HCV-mRNA. In addition, significantly (P < 0.001 raised serum p53 and tTG, and reduced bcl-2 were observed among HCV-positive patients as compared to HCV-negative patients and control patients. Conclusion: These results conclude that clinical severity of psoriasis is affected by the presence of HCV antibodies and overexpression of apoptotic related proteins. In addition, altered serum levels of apoptosis-regulating proteins could be useful prognostic markers and therapeutic targets of psoriatic disease.

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

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    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.

  20. 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...

  1. HCV genotyping using statistical classification approach

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. 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

  4. 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

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

    Directory of Open Access Journals (Sweden)

    Zafar Tariq

    2006-08-01

    Full Text Available Abstract Introduction HIV and HCV risk behaviors among injection drug users (IDUs in two urban areas in Pakistan were identified. Methods From May to June 2003, 351 IDUs recruited in harm-reduction drop-in centers operated by a national non-governmental organization in Lahore (Punjab province and Quetta (Balochistan province completed an interviewer-administered survey and were tested for HIV and HCV. Multivariable logistic regression identified correlates of seropositivity, stratifying by site. All study participants provided written, informed consent. Results All but two were male; median age was 35 and Discussion Despite no HIV cases, overall HCV prevalence was very high, signaling the potential for a future HIV epidemic among IDUs across Pakistan. Programs to increase needle exchange, drug treatment and HIV and HCV awareness should be implemented immediately.

  6. RT-PCR分析两厂家ELISA试剂检测血液抗-HCV的效果%Comparison of the accuracy of 2 anti-HCV antibody test kits by using RT-PCR analysis

    Institute of Scientific and Technical Information of China (English)

    罗均

    2003-01-01

    目的观察用两厂家ELISA试剂对血液抗-HCV检测的实际效果.方法应用两厂家ELISA抗-HCV试剂检测7000份献血者样本,并对阳性的42份血样用RT-PCR技术用HCV RNA分析.结果用两厂家试剂(ELISA法)同时检测血液抗-HCV,可提高抗-HCV阳性的检出率36%~43%;用PT-PCR技术对ELISA法检测抗-HCV阳性结果进行确证,证实两次检测可提高HCV检出率31%~41%.结论用两厂家ELISA法试剂初复二次检测血液的抗-HCV能提高对HCV的检出率.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Mohamed A Daw

    Full Text Available 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.

  11. Prevalence and correlates of HCV, HVB, and HIV infection among prison inmates and staff, Hungary.

    Science.gov (United States)

    Tresó, Bálint; Barcsay, Erzsébet; Tarján, Anna; Horváth, Gergely; Dencs, Agnes; Hettmann, Andrea; Csépai, Mária Magdolna; Gyori, Zoltán; Rusvai, Erzsébet; Takács, Mária

    2012-02-01

    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 to the survey, 1.5%, 4.9%, and 0.04% of the prisoners were tested positive for HBsAg, anti-HCV and anti-HIV, respectively. These prevalence data are among the lowest reported from prisons worldwide, although comparable to the Central European data. The prevalence of HBV, HCV, and HIV in the Hungarian prison staff was low (0.38%, 0.47%, and 0%, respectively). The rate of HCV infection was significantly higher among inmates who have ever injected drugs (22.5%) than among inmates who reported they had never injected drugs (1.1%). This first prevalence study of illegal drug injection-related viral infections among Hungarian prisoners points out that ever injecting drugs is the main reason for HCV infection among inmates. The opportunity to reach drug users infected with HCV for treatment underlines the importance of screening programs for blood-borne viruses in prisons. PMID:22143408

  12. 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.

  13. 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.

  14. 宁明县艾滋病哨点人群HIV、HCV、TP检测结果分析%Analysis on HIV,HCV and TP test results of AIDS sentinel surveillance population in Ningming

    Institute of Scientific and Technical Information of China (English)

    周梅; 王培育; 农幼丰; 向绍密; 黄洪浪

    2013-01-01

    目的 了解宁明县艾滋病(AIDS)哨点人群的人类免疫缺陷病毒(HIV)、丙型肝炎病毒(HCV)和梅毒螺旋体(TP)的感染情况,为制定相应疾病干预措施提供科学依据.方法 按照要求,对暗娼、吸毒者、孕产妇人群采集血样,用酶联免疫吸附试验(ELISA)检测 HIV、HCV、TP 抗体,并对其结果进行统计学处理.结果 2009~2012年哨点人群HIV、HCV和TP抗体分别检测4 599例、4 583例和4 525例,检出阳性分别为242例、1 073例和333例,阳性率分别为5.26%、23.41%和7.36%.暗娼、吸毒者、孕产妇HIV检出率分别为2.36%、14.06%和0.56%,差异有统计学意义(P<0.01),HCV检出率分别为4.23%、72.73%和0.31%,差异有统计学意义(P<0.01),TP检出率分别为8.8%、13.19%和0.94%,差异有统计学意义(P<0.01).结论 宁明县HIV、HCV、TP感染率最高的人群是吸毒人群,今后在防控中要加大力度对吸毒人群的监管.梅毒呈逐年上升趋势,迫切需要有针对性的行为干预和治疗,防止疫情的蔓延.%Objective To investigate the infection rates of HIV, HCV and syphilis among AIDS sentinel surveillance population in Ningming and provide scientific evidence for the development of appropriate prevention and control measures.Methods According to the National AIDS Sentinel Surveillance Implementation Plan, female sex workers, drug users and pregnant women blood samples were collected and KLISA was used to detect antibodies of HIV, HCV and TP.The detection results were statistically analyzed.Results During 2009-2012,4 599,4 583 and 4 525 cases were detected for antibodies of HIV,HCV and TP,and 242,1 073 and 333 cases were positive respectively with HIV,HCV and TP with positive rates of 5.26%,23.41% and 7.36% respectively.The HIV detection rates of female sex workers,drug users and pregnant women were 2.36%,14.06% and 0.56% respectively, with statistical significant differences(P<0.001).The HCV detection rates of female sex workers

  15. Sustained Virologic Response at 24 Weeks after the End of Treatment Is a Better Predictor for Treatment Outcome in Real-World HCV-Infected Patients Treated by HCV NS3/4A Protease Inhibitors with Peginterferon plus Ribavirin

    Science.gov (United States)

    Kanda, Tatsuo; Nakamoto, Shingo; Sasaki, Reina; Nakamura, Masato; Yasui, Shin; Haga, Yuki; Ogasawara, Sadahisa; Tawada, Akinobu; Arai, Makoto; Mikami, Shigeru; Imazeki, Fumio; Yokosuka, Osamu

    2016-01-01

    Background. Direct-acting antiviral agents against HCV with or without peginterferon plus ribavirin result in higher eradication rates of HCV and shorter treatment duration. We examined which is better for predicting persistent virologic response, the assessment of serum HCV RNA at 12 or 24 weeks after the end of treatment for predicting sustained virologic response (SVR12 or SVR24, respectively) in patients treated by HCV NS3/4A protease inhibitors with peginterferon plus ribavirin. Methods. In all, 149 Japanese patients infected with HCV genotype 1b treated by peginterferon plus ribavirin with telaprevir or simeprevir were retrospectively analyzed: 59 and 90 patients were treated with telaprevir- and simeprevir-including regimens, respectively. HCV RNA was measured by TaqMan HCV Test, version 2.0, real-time PCR assay. SVR12 or SVR24, respectively, was defined as HCV RNA negativity at 12 or 24 weeks after ending treatment. Results. Total SVR rates were 78.0% and 66.7% in the telaprevir and simeprevir groups, respectively. In the telaprevir group, all 46 patients with SVR12 finally achieved SVR24. In the simeprevir group, 60 (93.8%) of the total 64 patients with SVR12 achieved SVR24, with the other 4 patients all being previous-treatment relapsers. Conclusions. SVR12 was suitable for predicting persistent virologic response in almost all cases. In simeprevir-including regimens, SVR12 could not always predict persistent virologic response. Clinicians should use SVR24 for predicting treatment outcome in the use of HCV NS3/4A protease inhibitors with peginterferon plus ribavirin for any group of real-world patients chronically infected with HCV. PMID:27076789

  16. 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

  17. 献血者HBsAg及抗-HCV ELISA筛查不合格标本的假阳性分析%Evaluation on the false positive rate of unqualified donors with positive HBsAg and anti-HCV ELISA screen test

    Institute of Scientific and Technical Information of China (English)

    宋美兰; 任芙蓉; 龚晓燕; 王卓妍

    2013-01-01

    目的 了解献血者乙型肝炎表面抗原(HBsAg)及抗-丙型肝炎病毒(HCV)ELISA筛查不合格标本的假阳性情况.方法 对2009年2~5月常规国产和进口双试剂ELISA筛查HBsAg不合格的107份标本采用核酸和血清学中和试验加以确认,对常规国产和进口双试剂ELISA筛查抗-HCV不合格的184份标本采用核酸和血清学RIBA试验加以确认.核酸和(或)血清学补充试验阳性判为确认阳性,不能被确认阳性者判为假阳性.对假阳性情况进行统计分析.结果 HBsAg筛查不合格标本中,HBsAg ELISA双试剂阳性、单试剂阳性、灰区标本的假阳性率分别为2.0%、58.7%、63.6%,总假阳性率为32.7%;抗-HCV筛查不合格标本中,抗-HCV ELISA试剂假阳性率分别为23.9% 、95.2%、96.1%,总假阳性率为67.9%.HBsAg国产试剂单阳及灰区的假阳性率[78.6%(11/14),100%(3/3)]高于进口试剂单阳及灰区的假阳性率[50.0%(16/32),50.0% (4/8);x2=5.188,P<0.05];抗-HCV国产试剂单阳及灰区的假阳性率[96.3% (26/27),95.5% (21/22)]与进口试剂单阳及灰区的假阳性率[94.3% (33/35),93.5%(29/31)]差别不大(x2=1.048,P>0.05).结论 灰区标本的假阳性率极高,但从血液安全考虑灰区设置有必要;抗-HCV ELISA检测的假阳性问题较HBsAg ELISA严重;针对血液筛查假阳性问题,建议对血液及献血者应独立管理,建立献血者归队方案.目前HBsAg进口试剂的特异性优于国产试剂,而抗-HCV试剂的特异性进口试剂与国产试剂差别不大.

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

    Science.gov (United States)

    Bagheri Amiri, Fahimeh; Mostafavi, Ehsan; Mirzazadeh, Ali

    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 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. Findings 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. Conclusions 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. PMID:27031352

  19. Analysis of hepatitis non-treatment causes in a cohort of HCV and HCV/HIV infected patients

    Directory of Open Access Journals (Sweden)

    Karen Pereira

    2014-11-01

    Full Text Available Introduction: The decision to start hepatitis C virus (HCV treatment and its timing remains controversial. As new treatment regimens are approved, it is essential to identify patients eligible for each regimen in a timed and tailored approach. This study aims to identify the reasons to defer treatment of chronic hepatitis C infection in both HCV and HCV/HIV infected patients. Materials and Methods: Retrospective observational study of a cohort of HCV chronically infected patients with or without HIV infection, followed in an infectious disease clinic in Lisbon. Demographic, epidemiological, clinical, immunologic and virologic data were collected. Statistical analysis was performed with Microsoft Office®- Excel 2012. Kolmogorov-Smirnov, t-test, Chi-square and correlation analysis were performed for a significant p value<0.05. Results: The study included 669 patients, 225 patients infected with HCV (group A and 444 patients co-infected with HCV/HIV (group B. The comparative analysis of those groups (A vs. B showed: mean age was 49.4 years versus 46.9 (p<0.01, mean time since HCV diagnosis was 9.5 versus 14.6 years (p=0.558 both groups shared a male predominance and HCV acquisition due to intravenous drug use. Regarding genotype characterization, the predominant was 1a in both groups (p<0.01. Evaluation of IL28B polymorphism revealed CC 15.5% (A versus 9.45% (B (p<0.01. Group B mean TCD4 count was 585 cells/µL (mean percentage 27.1%. There was spontaneous viral clearance in 10.7% (A versus 4.1% (B (p<0.01. There were treated 52.0% (A versus 32.2% (B patients (p<0.01. For the untreated ones (107 – group A vs 270 – group B, no reason was identified for treatment deferral in 32.5% (A versus 48.0% (B patients. The most frequent reasons for deferring treatment were: withdrawal to follow-up (33.7%, active staging of disease (7.2%, alcohol abuse (6.0% and advanced age (6.0% in group A versus low TCD4 cell count (17.1%, loss to follow-up (7.5%, poor

  20. 抗-HCV与HCV-RNA检测结果不一致原因分析%Analysis of Reason That is Anti-HCV Accord with HCV-RNA

    Institute of Scientific and Technical Information of China (English)

    文汉成; 安社刚; 张红芳

    2004-01-01

    目的:探讨抗-HCV和HCV-RNA结果不一致的原因.方法:应用ELISA法和FQ-PCR法同步检测380例患者血清中抗-HCV和HCV-RNA.结果:在280例抗-HCV阳性中有106例HCV-RNA为阴性,有3例抗-HCV阴性患者HCV-RNA却为阳性.结论:同步检测抗-HCV和HCV-RNA可提高肝病患者HCV感染的检出率,为其诊断和治疗提供指导.

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

    Science.gov (United States)

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

    2004-05-01

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

  2. 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

  3. HCV/HIV共感染

    Institute of Scientific and Technical Information of China (English)

    施光峰

    2004-01-01

    由于共同的传播途径 ,HCV感染在HIV感染者中比较常见。这些人在开始有效抗逆转录病毒治疗(HARRT)后可能经历与HCV相关的逐渐升高的发病率和病死率。HIV感染对丙型肝炎的发展有不利影响 ,引起感染后增强的病毒抵抗和高水平的病毒血症 ,加速HCV相关肝病的发展。同样 ,丙型肝炎也可以影响HIV感染的病程和处理。美国有 15万到 30万人同时感染了HIV和HCV ,占所有HIV感染者的 15 %~ 30 %和所有HCV感染者的 5 %~ 10 %。过去认为 ,HCV感染是HIV感染者中的一个相对次要的医学问题 ,HAART的应用使大多数机会性疾病的发生率大大降低 ,丙型肝炎随之日益成为这些患者致病和死亡的一个重要原因。一、流行病学全球HCV的感染率约为 3% ,即 1.7亿人左右 ,我国HCV的感染率约为 2 .2 % ,美国的HCV感染率估计在 1.8%左右 ,即相当于 390万人。在这些人中 ,大约 2 70万为慢性HCV感染 ,其中有 30万人同时感染HIV ,这一数字占所有HIV感染者的近 30 %和所有HCV感染者的 10 %。HIV和HCV有共同的传播途径 ,即静脉传播、性接触传播和垂直传播。这...

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

    Directory of Open Access Journals (Sweden)

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Detection of HCV-RNA by Reverse Transcription Polymerase Chain Reaction Using Biotinylated and Radioiodinated Primers

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jin Sook; Moon, Dae Hyuk; Cheon, Jun Hong; Chung, Yoon Young; Park, Hung Dong; Chung, Young Hwa; Lee, Young Sang [Asan Medical Center, University of Ulsan, Seoul (Korea, Republic of)

    1994-07-15

    This study was performed to evaluate the clinical applicability of the reverse transcription polymerase chain reaction (RT-PCR) kit of HCV-RNA using biotinylated and radioiodinated primers. Study subjects were 118 patients with positive anti-HCV. HCV-RNA in patients serum was extracted by guanidium thiocyanate method. After first amplification, the product was reamplified by primers labelled with biotin and I-125. The final amplification product was detected by counting the radioactivity after incubation in avidin coated tubes. In 51 samples, the test was repeated for evaluation of reproducibility. This new method was also compared with conventional RT-PCR methods in 34 samples from patients with chronic liver disease. The results were as follows, 1) HCV-RNA was positive in 85(97%)of 88 patients with chronic liver disease, and in 23 (73%) of 30 patients with normal liver function. 2) In comparison with conventional method, HCV-RNA was detected in 32(94%) of 34 patients with new method, whereas in 27(79% ) of the same group with conventional method 3) Repeated test with new method in 52 samples demonstrated 82% of concordant result. In conclusion, new method with biotinylated and radioiodinated primers was more sensitive than conventional method. However, great care must be taken for quality control because there were considerable interassay variation and possibility of false positivity and false negativity.

  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. 抗-HCV和HCV-RNA检测及其与ALT的相关性分析%Quantitative analysis of serum anti-HCV, HCV-RNA and ALT

    Institute of Scientific and Technical Information of China (English)

    贾珉; 邵芳

    2012-01-01

    目的 探讨化学免疫发光法(CLIA)定量检测抗-HCV和FQ-PCR法检测HCV-RNA含量与丙氨酸氨基转移酶(ALT)水平的相关性.方法 用CLIA定量筛选抗-HCV阳性的100例病人标本,以荧光定量PCR法检测HCV-RNA含量和酶速率法检测ALT浓度水平,并对所得数据进行统计分析.结果 在100份抗-HCV阳性标本中,检出HCV-RNA阳性者76例,阳性率为76%.随着抗-HCV的S/CO值增高,HCV-RNA检出率增高较明显;ALT水平与HCV-RNA含量无显著相关性(P>0.05),但ALT异常率与HCV-RNA含量呈正相关.结论 在HCV诊断与疗效观察中,血清抗HCV、HCV-RNA和ALT指标各有利弊,3者有机结合能正确诊断和预测肝脏损伤及评价疗效.%Objective To analyze the correlation among the quantitative detection of serum anti-HCV by chemiluminescene immunoassay(CLIA), the content of HCV-RNA and alanine aminotransferase (ALT) levels. Methods The sera from 100 patients with CLIA positive results were used in this study. The level of serum HCV-RNA and ALT was detected by real-lime fluorescent quantitative assay (FQ-PCR) and enzyme-rate method, respectively. The data were analyzed by statistical method. Results 76 patients were found HCV-RNA positive, with a positive rate of 76%. The HCV-RNA positive rate was positively correlated with the anti-HCV S/CO result. There was no correlation between the level of ALT and the content of HCV-RNA (P>0.05), but the content of HCV-RNA was correlated with the ALT. Conclusion The level of anti-HCV antibody,HCV-RNA and ALT should all be used in the diagnosis of HCV. An appropriate combination of these indexes has important clinical significance in the diagnosis, prediction of liver injury and early treatment.

  10. 联合检测血清HCV RNA载量、HCV cAg和HCV Ab在HCV感染诊断中的临床意义

    Institute of Scientific and Technical Information of China (English)

    毛小红

    2015-01-01

    目的:探讨HCV RNA载量、HCV cAg和HCV Ab的联合检测在HCV感染早期诊断中的临床意义。方法采用荧光定量聚合酶链反应(FQ-PCR)技术检测HCV-RNA含量,并用ELISA对标本进行HCV cAg和HCV Ab的检测。比较108例丙型肝炎患者 HCV RNA 载量、HCV cAg和 HCV Ab 的检出率。结果HCV-RNA的阳性检出率为91.75%,显著高于HCV cAg的71.42%(χ2=25.042,P<0.01)和 HCV Ab 的69.78%(χ2=28.299,P<0.01)。3例HCVcAg阳性而HCV RNA和HCV Ab均阴性;6例HCV Ab 阴性而HCV-RNA和HCV cAg检测结果均阳性;8例HCV-RNA阳性而HCV Ab和HCV cAg检测结果均阴性;不同HCV RNA载量间HCVcAg和HCV Ab检测阳性率差异均无统计学意义(χ2=0.016、0.046,均 P>0.05)。结论联合检测HCV RNA、HCV cAg和HCV Ab对HCV感染的早期准确诊断具有重要意义和价值。

  11. Human Transbodies to HCV NS3/4A Protease Inhibit Viral Replication and Restore Host Innate Immunity

    Science.gov (United States)

    Jittavisutthikul, Surasak; Seesuay, Watee; Thanongsaksrikul, Jeeraphong; Thueng-in, Kanyarat; Srimanote, Potjanee; Werner, Rolf G.; Chaicumpa, Wanpen

    2016-01-01

    A safe and effective direct acting anti-hepatitis C virus (HCV) agent is still needed. In this study, human single chain variable fragments of antibody (scFvs) that bound to HCV NS3/4A protein were produced by phage display technology. The engineered scFvs were linked to nonaarginines (R9) for making them cell penetrable. HCV-RNA-transfected Huh7 cells treated with the transbodies produced from four different transformed E. coli clones had reduced HCV-RNA inside the cells and in the cell spent media, as well as fewer HCV foci in the cell monolayer compared to the transfected cells in culture medium alone. The transbodies-treated transfected cells also had up-expression of the genes coding for the host innate immune response, including TRIF, TRAF3, IRF3, IL-28B, and IFN-β. Computerized homology modeling and intermolecular docking predicted that the effective transbodies interacted with several critical residues of the NS3/4A protease, including those that form catalytic triads, oxyanion loop, and S1 and S6 pockets, as well as a zinc-binding site. Although insight into molecular mechanisms of the transbodies need further laboratory investigation, it can be deduced from the current data that the transbodies blocked the HCV NS3/4A protease activities, leading to the HCV replication inhibition and restoration of the virally suppressed host innate immunity. The engineered antibodies should be tested further for treatment of HCV infection either alone, in combination with current therapeutics, or in a mixture with their cognates specific to other HCV proteins. PMID:27617013

  12. DC-SIGN:Binding receptor for HCV?

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hua Feng; Quan-Chu Wang; Qing-He Nie; Zhan-Sheng Jia; Yong-Xin Zhou

    2004-01-01

    DC-SIGN, a dendritic Cell-specific adhesion receptor and a type Ⅱ transmembrane mannose-binding C-type lectin, is very important in the function of DC, both in mediating naive T cell interactions through ICAM-3 and as a rolling receptor that mediates the DC-specific ICAM-2-dependent migration processes. It can be used by viral and bacterial pathogens including Human Immunodeficiency Virus (HIV), HCV, Ebola Virus, CMV and Mycobacterium tuberculosis to facilitate infection. Both DC-SIGN and DC-SIGNR can act either in cis,by concentrating virus on target cells, or in trans, by transmission of bound virus to a target cell expressing appropropriate entry receptors. Recent work showed that DC-SIGN are highaffinity binding receptors for HCV. Besides playing a role in entry into DC, HCV E2 interaction with DC-SIGN might also be detrimental for the interaction of DC with T cells during antigen presentation. The clinical strategies that target DCSIGN may be successful in restricting HCV dissemination and pathogenesis as well as directing the migration of DCs to manipulate appropriate immune responses in autoimmunity and tumorigenic situations.

  13. HCV/HTLV coinfection: Does HTLV-1 interfere in the natural history of HCV-related diseases?

    Science.gov (United States)

    Silva, Marcelo Costa; Silva, Carolina Alves Costa; Machado, Gustavo Uzêda; Atta, Ajax; M Freire, Songeli; Carvalho, Edgar; Schinoni, Maria Isabel; Paraná, Raymundo

    2016-11-01

    Hepatitis C virus (HCV) and human T-lymphotropic virus type 1 (HTLV-1) coinfection occurs in many regions. However, few studies have focused on the natural history of HCV-induced liver disease in coinfected patients. To describe the clinical, epidemiological, and histopathological aspects of HTLV-1/HCV coinfection in Brazil. A cross-sectional study with 23 patients coinfected with HCV/HTLV. The control groups consisted of 21 patients monoinfected with HCV and 20 patients monoinfected with HTLV-1. The cytokine profiles (Th1 and Th2 cell responses), clinical, laboratory features, and histopathological aspects were examined. The control group for cytokine analysis validation consisted of patients monoinfected with HTLV, and a fourth group consisted of healthy blood donors. No anthropometric differences present between the three infected groups. We observed higher serum concentrations of IFN-γ in patients coinfected with HCV/HTLV-1 than those in HCV monoinfected patients. The HCV/HTLV-1 coinfected group also exhibited a higher degree of liver steatosis than the HCV monoinfected patients. Results suggest that HCV/HTLV-1 coinfection may result in a different pattern of HCV infection due to the immunologic disorders likely associated with HTLV-1, but there is no clear evidence of the HTLV role in the natural history of HCV infection. J. Med. Virol. 88:1967-1972, 2016. © 2016 Wiley Periodicals, Inc.

  14. Association of interleukin-12 p40 gene 3'-untranslated region polymorphism and outcome of HCV infection

    Institute of Scientific and Technical Information of China (English)

    Li-Min Yin; Qi-Xin Wang; Yan Gao; Hui Zhuang; Wan-Fu Zhu; Lai Wei; Xiao-Yuan Xu; De-Gui Sun; Yan-Bin Wang; Wen-Mei Fan; Min Yu; Xiu-Lan Tian

    2004-01-01

    AIM: To investigate the effect of interleukin-12 p40 gene (IL12B) 3'-untranslated region polymorphism on the outcome of HCV infection.METHODS: A total of 133 patients who had been infected with HCV for 12-25 (18.2±3.8) years, were enrolled in this study. Liver biochemical tests were performed with an automated analyzer and HCV RNA was detected by fiuorogenic quantitative polymerase chain reaction. B-mode ultrasound was used for liver examination. Polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) was used for the detection of IL12B (1188A/C) polymorphism.RESULTS: Self-limited infection was associated with AC genotype (OR = 3.48; P = 0.001) and persistent infection was associated with AA genotype (OR = 0.34; P = 0.014)at site 1188 of IL12B. In patients with persistent HCV infection, no significant differences were found regarding the age, gender, duration of infection and biochemical characteristics (P>0.05). According to B-mode ultrasound imaging and clinical diagnosis, patients with persistent infection were divided into groups based on the severity of infection. No significant differences were found in the frequency of IL-12 genotype (1188A/C) between different groups (P>0.05).CONCLUSION: The polymorphism of IL12B (1188A/C)appears to have some influence on the outcome of HCV infection.

  15. 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

  16. Factors Influencing Uptake of Rapid HIV and Hepatitis C Screening Among Drug Misusing Adult Emergency Department Patients: Implications for Future HIV/HCV Screening Interventions.

    Science.gov (United States)

    Merchant, Roland C; DeLong, Allison K; Liu, Tao; Baird, Janette R

    2015-11-01

    In this randomized, controlled trial among 957 English- or Spanish-speaking drug misusing adult emergency department (ED) patients, we determined if a tailored brief intervention (BI) increased uptake of rapid HIV/HCV screening, and identified factors associated with greater screening uptake. Rapid HIV/HCV screening uptake was greater in the control than the BI arm (45 vs. 38 %; p Screening uptake depended on elapsed study time and which research staff member offered testing. In the control arm, uptake was lowest for those spending screening uptake generally increased over time. Tailored BI content specifically addressing participant HIV/HCV knowledge, HIV/HCV risk behaviors, or need for HIV/HCV screening was not associated with greater screening uptake. These study findings suggested factors that should be considered when designing future ED-based screening initiatives, such as elapsed study time, who offers testing, and the content of interventions.

  17. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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。

  20. Analysis of the results of external quality assessment for hepatitis C virus RNA tests%从全国室间质量评价结果探讨HCV RNA检测中的问题

    Institute of Scientific and Technical Information of China (English)

    张瑞; 王露楠; 张括; 谢洁红; 孙宇; 李金明

    2013-01-01

    目的 评价2012年第一次HCV RNA检测的全国室间质量结果,以分析探讨我国临床实验室HCV RNA检测中存在的问题,为进一步改进和提高实验室检测质量提供依据.方法 卫生部临检中心(以下简称“部中心”)2012年共发放5份样本至927家参评实验室,其中1份为阴性,4份为与国际标准物质比对定值的内含HCVRNA相应片段的病毒样颗粒.参评实验室按照规定的时间检测样本,并向部中心回报结果.然后,计算所有参评实验室和各检测试剂(实验室数≥5家)对每份质评样本定性和定量检测的符合率.计算总体参评实验室和不同试剂对阳性样本检测的均值(GM)和标准差(s).将所有参评实验室和不同试剂检测的GM和靶值比较,绘制相关性曲线.结果 参评实验室检测1211、1212、1213、1214号样本定性结果的符合率分别为99.5% (403/405)、98.5%(400/406)、100.0% (405/405)、100.0%(406/406),阴性样本的符合率为99% (401/405);检测1211、1212和1213号样本定量结果的符合率相近,分别为93.8%(549/585)、92.3% (541/586)和94.5%(554/586),HCV RNA浓度最高的1214号样本符合率仅为87.7% (514/586).试剂A对1214号样本定量符合率仅为67.2% (92/137).总体参评实验室HCV RNA定量结果GM(1211、1212、1213和1214号样本GM分别为4.63、4.11、5.41和6.23)与靶值(1211、1212、1213和1214号样本靶值对数值分别为4.64、4.16、5.40和6.20)结果非常接近.试剂C、试剂E和试剂G的GM均与靶值不一致,试剂C检测1211、1212、1213和1214号样本的GM依次为4.22、3.56、5.16和5.90,试剂E检测1211、1212、1213和1214号样本的GM依次为4.52、3.78、5.55和6.29,试剂G检测1211、1212、1213和1214号样本的GM依次为4.83、4.36、5.72和6.56.结论 临床实验室定性和定量检测HCV RNA的结果较为理想.但在检测试剂和临床实验室检测过程中,仍存在试剂GM与靶值偏差较大、使用同一试

  1. 抗-HCV与HCV-RNA和ALT之间的关系探讨%Discussion on the Relationship of Anti-HCV, HCV-RNA and ALT

    Institute of Scientific and Technical Information of China (English)

    甸子芩; 沈云松

    2012-01-01

      目的探讨丙型肝炎病毒感染者丙型肝炎病毒抗体(抗-HCV)与丙型肝炎病毒核酸(HCV-RNA)和丙氨酸转氨酶(ALT)之间的关系.方法 对抗-HCV阳性样本441例,采用荧光定量聚合酶链反应(RT-PCR)检测HCV-RNA含量和其ALT水平.结果 441例抗-HCV阳性的血清中HCV-RNA阳性的有295例,阳性率67%,HCV-RNA阳性率随抗-HCV的S/CO值升高而升高.ALT异常的有269例,阳性率61%,ALT的含量及阳性率随HCV-RNA的含量升高而升高.结论 HCV-RNA的阳性率与抗-HCV的S/CO值存在正相关,ALT的阳性率及含量与HCV-RNA呈正相关,因此,可根据抗-HCV检测的S/CO值及ALT的含量辅助临床了解丙型肝炎病毒在体内的复制情况,以指导治疗.%  Objective To investigate the relationship of hepatitis C virus antibody (anti-HCV), hepatitis C virus RNA (HCV-RNA) and alanine amino transferase (ALT) in hepatitis C virus infection. Methods Using fluorescence quantitative polymerase chain reaction (RT-PCR) detecting HCV-RNA content and testing ALT levels in 441 cases of anti-HCV positive samples. Results In 441 cases of anti-HCV positive serum, HCV-RNA positive 295 cases, the positive rate of HCV-RNA was 67%, and the positive rate increased with the anti-HCV S/CO ratio increased. Abnormal ALT 269 cases, the positive rate of ALT was 61%, the content and the positive rate of ALT increased with HCV-RNA levels increased. Conclusion The positive rate of HCV-RNA has positive correlation with anti-HCV S/CO ratio, the positive rate and content of ALT has positive correlation with HCV-RNA, therefore, according to the anti-HCV S/CO ratio and the content of ALT assisted clinical understand the replication of hepatitis C virus in the body, to guide treatment.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. HCV抗原检测与HCV-RNA和HCV抗体检测的比较研究%Comparative Study on the Detection of HCV-Antigen, HCV-RNA and HCV-Antibody Detection

    Institute of Scientific and Technical Information of China (English)

    李妙羡; 王香玲; 吴晓康; 卢洁; 王小利; 尹佳峰; 孟昊

    2012-01-01

    Objective To study the value of measurement of HCV antigen, HCV antibody and HCV-RNA in the clinical diagnosis of Hepatitis. Methods HCV antigen would adopt double antibody sandwiched method; HCV-RNA would employ the real-time fluorescence quantitative PCR technique, HCV antibody would use the technology of Enzyme-Linked Immunosor-bent Assay (ELISA) ,44 specimens of positive HCV antibody would be detected with HCV antigen and HCV-RNA measurement. Results Among the specimens of positive HCV antibody, the rate of positive HCV antigen was measured as 43. 2%;the rate of positive HCV-RNA was measured as 82. 5%. Among the specimens of positive HCV-RNA,the rate of positive HCV antigen was measured as 45. 5%. Conclusion In the three kinds of Hepatitis markers,it was the most reliable method to judge whether infected with Hepatitis by using the real-time fluorescence quantitative PCR technique to measure HCV-RNA. If HCV antigen was used to diagnose Hepatitis, there was still 54. 5% rate of missed detection. Hence,there exists a long distance from the application in the clinical practice. In the hospitals where it was impossible to employ the realtime fluorescence quantitative PCR technique to measure HCV-RNA,when confirming the specimens of positive HCV antibody with HCV antigen and judging past exposure or present exposure to HCV,index of liver function and clinical manifestation should be combined to make a clear and definite diagnosis.%目的 评价丙型肝炎病毒核心抗原(HCV抗原)、丙型肝炎病毒抗体(HCV抗体)及丙型肝炎病毒RNA(HCV-RNA)三种检测方法在丙型肝炎实验室诊断中的作用.方法 HCV抗原采用双抗体夹心法;HCV-RNA采用实时荧光定量PCR技术(RT-PCR),HCV抗体采用酶联免疫技术(间接法),对44例HCV抗体阳性标本进行HCV抗原和HCV-RNA检测.结果 在HCV抗体阳性标本中,HCV抗原阳性检出率为43.2%,HCV-RNA阳性检出率为82.5%;在HCV-RNA阳性标本中,HCV抗原阳性检出率为45

  4. 丙型肝炎核心抗原检测在丙型肝炎诊断中的意义%Detection of HCV core antigen and its diagnostic significance

    Institute of Scientific and Technical Information of China (English)

    杨杰; 崔敬; 刘春; 魏枫华; 窦晓光

    2013-01-01

    目的 了解丙型肝炎核心抗原(HCV-cAg)检测方法的敏感性及特异性,确定具有临床意义的S/CO值,探讨其在丙型肝炎诊断中的意义.方法 使用ELASA方法检测丙型肝炎核心抗原,RT-PCR检测HCV RNA定量,观察不同S/CO值所对应的HCV RNA定量之间的关系,以HCV RNA为诊断金标准,列四格表做诊断实验.结果 HCV-cAg抗原检测的敏感性为87.05%,特异性为76.67%,阳性预测值为96.53%,阴性预测值为44.23%.结论 (1)随着HCV-cAg的S/CO值逐渐增大,其与HCV RNA阳性符合率明显增高,随着HCV-cAg的S/CO值减小,其与HCV RNA阴性符合率明显增高;(2)S/CO值=2可以作为临床判断HCV感染病毒血症存在的一个标准;(3)本实验的敏感性和特异性较好,检测方法简单,可以作为丙型肝炎临床诊断的补充试验及筛查.%Objective To compare the abilities of the hepatitis C virus (HCV) core antigen (cAg) test and the HCV RNA assay for confirming anti - HCV presence in order to determine the clinical utility of the HCV - cAg as an alternative or confirmatory diagnostic tool. Methods Serum samples collected from 158 patients diagnosed with HCV infection were subjected to the enzyme - linked immunosorbent assay - based HCV — cAg test. The optical density ( OD) measured values were used to calculate the ratio of specimen absorbance to the cutoff value (S/ CO). Simultaneously, the serum samples were subjected to PCR - based nucleic acid amplification quantitative fluorescence detection of HCV RNA. Results None of the serum samples had a S/CO value 5 ( 100% positive). The HCV - cAg test sensitivity was 87. 05% , specificity was 76. 67% , positive predictive value was 96. 53% , and negative predictive value was 44. 23% . As the S/CO value gradually increased, the significantly higher positive coincident rate of the HCV RNA test decreased. The HCV RNA negative coincident rate was significantly higher than that of the HCV - cAg test. HCV - cAg S/CO values

  5. Stability of hepatitis C virus (HCV) RNA levels among interferon-naïve HIV/HCV-coinfected individuals treated with combination antiretroviral therapy

    DEFF Research Database (Denmark)

    Grint, D; Peters, L; Reekie, J;

    2013-01-01

    Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. High HCV RNA levels have been associated with poor treatment response. This study aimed to examine the natural history of HCV RNA in chronically HCV/HIV-coinfected individuals.......Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. High HCV RNA levels have been associated with poor treatment response. This study aimed to examine the natural history of HCV RNA in chronically HCV/HIV-coinfected individuals....

  6. Conversion from Tacrolimus to Cyclosporine A Improves Glucose Tolerance in HCV-Positive Renal Transplant Recipients.

    Directory of Open Access Journals (Sweden)

    Ammon Handisurya

    Full Text Available Calcineurin-inhibitors and hepatitis C virus (HCV infection increase the risk of post-transplant diabetes mellitus. Chronic HCV infection promotes insulin resistance rather than beta-cell dysfunction. The objective was to elucidate whether a conversion from tacrolimus to cyclosporine A affects fasting and/or dynamic insulin sensitivity, insulin secretion or all in HCV-positive renal transplant recipients.In this prospective, single-center study 10 HCV-positive renal transplant recipients underwent 2h-75g-oral glucose tolerance tests before and three months after the conversion of immunosuppression from tacrolimus to cyclosporine A. Established oral glucose tolerance test-based parameters of fasting and dynamic insulin sensitivity and insulin secretion were calculated. Data are expressed as median (IQR.After conversion, both fasting and challenged glucose levels decreased significantly. This was mainly attributable to a significant amelioration of post-prandial dynamic glucose sensitivity as measured by the oral glucose sensitivity-index OGIS [422.17 (370.82-441.92 vs. 468.80 (414.27-488.57 mL/min/m2, p = 0.005, which also resulted in significant improvements of the disposition index (p = 0.017 and adaptation index (p = 0.017 as markers of overall glucose tolerance and beta-cell function. Fasting insulin sensitivity (p = 0.721, insulinogenic index as marker of first-phase insulin secretion [0.064 (0.032-0.106 vs. 0.083 (0.054-0.144 nmol/mmol, p = 0.093 and hepatic insulin extraction (p = 0.646 remained unaltered. No changes of plasma HCV-RNA levels (p = 0.285 or liver stiffness (hepatic fibrosis and necroinflammation, p = 0.463 were observed after the conversion of immunosuppression.HCV-positive renal transplant recipients show significantly improved glucose-stimulated insulin sensitivity and overall glucose tolerance after conversion from tacrolimus to cyclosporine A. Considering the HCV-induced insulin resistance, HCV-positive renal transplant

  7. Cytokines and HCV-Related Disorders

    Directory of Open Access Journals (Sweden)

    Poupak Fallahi

    2012-01-01

    However, HCV interferes with cytokines at various levels and escapes immune response by inducing a T-helper (Th2/T cytotoxic 2 cytokine profile. Inability to control infection leads to the recruitment of inflammatory infiltrates into the liver parenchyma by interferon (IFN-gamma-inducible CXC chemokine ligand (CXCL-9, -10, and -11 chemokines, which results in sustained liver damage and eventually in liver cirrhosis. The most important systemic HCV-related extrahepatic diseases—mixed cryoglobulinemia, lymphoproliferative disorders, thyroid autoimmune disorders, and type 2 diabetes—are associated with a complex dysregulation of the cytokine/chemokine network, involving proinflammatory and Th1 chemokines. The therapeutical administration of cytokines such as IFN-alpha may result in viral clearance during persistent infection and reverts this process.

  8. 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...

  9. The Novel Cyclophilin Inhibitor CPI-431-32 Concurrently Blocks HCV and HIV-1 Infections via a Similar Mechanism of Action.

    Directory of Open Access Journals (Sweden)

    Philippe A Gallay

    Full Text Available HCV-related liver disease is the main cause of morbidity and mortality of HCV/HIV-1 co-infected patients. Despite the recent advent of anti-HCV direct acting antivirals (DAAs, the treatment of HCV/HIV-1 co-infected patients remains a challenge, as these patients are refractory to most therapies and develop liver fibrosis, cirrhosis and liver cancer more often than HCV mono-infected patients. Until the present study, there was no suitable in vitro assay to test the inhibitory activity of drugs on HCV/HIV-1 co-infection. Here we developed a novel in vitro "co-infection" model where HCV and HIV-1 concurrently replicate in their respective main host target cells--human hepatocytes and CD4+ T-lymphocytes. Using this co-culture model, we demonstrate that cyclophilin inhibitors (CypI, including a novel cyclosporin A (CsA analog, CPI-431-32, simultaneously inhibits replication of both HCV and HIV-1 when added pre- and post-infection. In contrast, the HIV-1 protease inhibitor nelfinavir or the HCV NS5A inhibitor daclatasvir only blocks the replication of a single virus in the "co-infection" system. CPI-431-32 efficiently inhibits HCV and HIV-1 variants, which are normally resistant to DAAs. CPI-431-32 is slightly, but consistently more efficacious than the most advanced clinically tested CypI--alisporivir (ALV--at interrupting an established HCV/HIV-1 co-infection. The superior antiviral efficacy of CPI-431-32 over ALV correlates with its higher potency inhibition of cyclophilin A (CypA isomerase activity and at preventing HCV NS5A-CypA and HIV-1 capsid-CypA interactions known to be vital for replication of the respective viruses. Moreover, we obtained evidence that CPI-431-32 prevents the cloaking of both the HIV-1 and HCV genomes from cellular sensors. Based on these results, CPI-431-32 has the potential, as a single agent or in combination with DAAs, to inhibit both HCV and HIV-1 infections.

  10. Aktuelles Management der HIV/HCV-Koinfektion

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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...

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Ddetection of HCV RNA in ELISA anti-HCV negative donors%ELISA抗-HCV阴性献血者HCV RNA的检测

    Institute of Scientific and Technical Information of China (English)

    纪勇平; 雷永良; 吴丽雅; 任振唤

    2002-01-01

    @@ 自酶联免疫法(ELISA)检测丙型肝炎病毒抗体(抗-HCV)试剂应用于血液HCV 的初筛以来,血液HCV的传播风险大为降低,但是仍有少数患者输血后感染HCV,原因是由于ELISA本身的局限性而使部分"窗口期"的HCV感染者未能被检出.为了解本市ELISA筛查合格献血者血液HCV RNA 的流行率,笔者对部分经ELISA双份试剂检测阴性的标本进行HCV RNA 检测,现报告如下.

  17. ALT与HCV核心抗原及HCV-RNA相关性研究%Study on correlation of ALT, HCV core antigen and HCV-RNA

    Institute of Scientific and Technical Information of China (English)

    王锐; 曹培义

    2013-01-01

    目的 研究ALT与HCV核心抗原、HCV-RNA间关系.方法 对81例HCV-RNA阳性标本检测HCV核心抗原和ALT水平.结果 81例HCV-RNA阳性标本检出HCV核心抗原阳性32例,灰区26例,ALT水平超过临床参考值56例,ALT检测水平与HCV核心抗原阳性程度呈正相关性.结论 HCV-cAg仅与HCV-RNA复制密切相关,与复制水平无关.HCV核心抗原可联合HCV抗体检测提高血液标本HCV感染检出率,结合ALT可以评测感染状态.

  18. Virological Mechanisms in the Coinfection between HIV and HCV

    Directory of Open Access Journals (Sweden)

    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.

  19. Viral genotype and HLA class II alleles influence on extra-hepatic manifestations of chronic HCV infection

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    M. Galeazzi

    2011-09-01

    Full Text Available Objective: To test whether an association between HCV genotype, HLA class II alleles distribution and extra-hepatic manifestations (EHM can be demonstrated in a group of Italian patients with chronic HCV infection . Methods: Sixty patients affected by HCV infection with EHM were consecutively enrolled. 163 HCV patients without EHM were tested as controls for the prevalence of HCV genotypes, while we referred to literature as to the controls for HLA distribution. HCV-RNA was quantified by a RT-PCR. HLA class II alleles typing was performed using a standard microlymphocytotoxicity assay. We used chi-square or Fisher test (p<0.05 significant. Odds Ratio (OR was performed by 2X2 contingency table. Results: HCV 2c genotype was found in 63.46% of patients compared to 19.63% of controls (p<0.0001; OR=7.11. Furthermore, it correlated with carpal tunnel syndrome (p=0.03; OR=4.5 and autoimmune thyroiditis (p=0.02; OR=9.2. On the contrary, 1b genotype protected from EHM in toto (p=0.0004; OR=0.21 and particularly from carpal tunnel syndrome (p=0.0014; OR=0.07. Moreover, 3a genotype prevented HCV people from having cryoglobulinemia (p=0.05; OR=0.11. As to HLA, DR6 seemed to facilitate EHM in HCV patients (p=0.041; OR=1.61, while DQ2 (p=0.03; OR=0.5 and DQ3 (p=0.002; OR= 0.5 may play a protective role. In addition, HLA DR3 was associated with cryoglobulinemia (p=0.02; OR=9.5. Conclusions: According to our findings, 2c genotype can be considered as a major risk factor for developing HCVrelated EHM, while 1b genotype seems to prevent their onset; there are also evidences suggesting that HLA might play a role in chronic HCV infected patients.

  20. Longitudinal study of a human drug-induced model of autoantibody to cytoplasmic rods/rings following HCV therapy with ribavirin and interferon-α.

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    Gerson Dierley Keppeke

    Full Text Available BACKGROUND: A novel pattern in the indirect immunofluorescence antinuclear antibody assay on HEp-2 cells (IIF-HEp-2 characterized by cytoplasmic rods and rings (RR was reported in HCV patients, but stringent disease specificity studies and longitudinal analysis are lacking. We investigated the clinical significance of anti-RR in an HCV cohort with up to a 12-month treatment follow up. METHODOLOGY/RESULTS: 597 patients (342 HCV, 55 HCV/HIV, 200 non-HCV were screened and titered for anti-RR. Serial samples were available from 78 of 176 treated and 27 of 166 untreated patients. Anti-RR was detected in 14.1% of 342 HCV patients, 9.1% of 55 HCV/HIV, 3.4% of 29 Hepatitis B, and none of 171 non-HCV (p47% tested positive for anti-RR. The anti-RR titer generally increased with sustained treatment and remained high in 53% of patients. After treatment, anti-RR titer was negative in 41%. Non-responders to HCV therapy were 77% in anti-RR-positive versus 64% in anti-RR-negative patients. Response to treatment was not associated with anti-RR titer or the dynamics of anti-RR reactivity during and after treatment. CONCLUSIONS: The exquisite association of anti-RR reactivity with combined interferon-α/ribavirin therapy in HCV patients represents a unique model for drug-induced autoantibody generation in humans as demonstrated by the fact that a significant fraction of patients who have anti-RR during therapy becomes anti-RR-negative after completion of therapy.

  1. 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

  2. Prevalence of HCV Infections and Co-Infection With HBV and HIV and Associated Risk Factors Among Addicts in Drug Treatment Centers, Lorestan Province, Iran

    Science.gov (United States)

    Norouzian, Hossein; Gholami, Mohammadreza; Shakib, Pegah; Goudarzi, Gholamreza; Ghobadian Diali, Hamze; Rezvani, Azam

    2016-01-01

    Background: Hepatitis C is an infectious disease caused by blood-borne pathogen, hepatitis C virus (HCV). Objectives: The purpose of this study was to investigate the prevalence of HCV infection and associated risk factors among addicts in drug treatment centers in Lorestan Province, Iran. Patients and Methods: A cross-sectional sero-behavioral survey was given to drug addicts in the drug treatment centers of Khorramabad, Lorestan Province, Iran during June 2012 - March 2013. Drug addicts were interviewed using a standard questionnaire including demographic, imprisonment history, and HCV-related risk behavior items. Thereafter, the sera drawn from the participants were tested for anti-HCV antibody (Ab), anti-human immunodeficiency virus (HIV) Ab, and hepatitis B surface antigen (HBsAg). Results: The mean age of the cohorts was 31.7. Up to 60.2% of drug users had educational levels less than high school, 67.5% were self-employed, and 32.5% were office workers. The mean duration of drug injection was 6.8 years. Statistical analyses indicated that the prevalence of HCV among drug addicts was positively associated with age, past incarceration, drug injection history, the duration of drug use, and tattooing. In addition, 16.23% of volunteers were HCV-positive. Of those infected with HCV, 1.10% was co-infected with HBV, 2.95% were positive for HIV, and 0.36% of HCV-positive cases were infected with all three viruses. Conclusions: The high prevalence of HCV infection among this group implies a high rate of transmission and exposure to the risk of serious diseases. It is important that the high prevalence of HCV infection be taken into consideration to control further transmission of this infection. PMID:27162762

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

    DEFF Research Database (Denmark)

    Merkinaite, Simona; Lazarus, Jeff; Gore, Charles

    2008-01-01

    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...... 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...

  4. HCV replication in PBMC and its influence on interferon therapy

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

    AIM: To study hepatic virus C (HCV) RNA and HCV proteinexpression in peripheral blood mononuclear cells (PBMCs)of patients with HCV infection, and explore the relationshipbetween the HCV RNA in the PBMCs and response tointerferon (IFN) therapy.METHODS: Type-specific primers were designed and RT-nested PCR was used to detect the plus- and minus- strandsof HCV RNA in PBMCs of 54 patients with HCV infection;Indirect immunofluorescence assay was applied to identifyHCVNS5 protein expression in PBMCs; 6 month-, 3 MU-IFNregiment was administrated to observe the responses toIFN in 35 chronic hepatitis C patients with different HCVRNA status in PBMCs.RESULTS: HCV plus strand RNA was found in 10 of 19(52.6 %) acute hepatitis C patients and 22 of 35 (62.9 %)chronic hepatitis C patients. HCV minus strand RNA wasdetected in 14 of 35 (40.0 %) chronic hepatitis C patients,but only one patient (5.3 %) with acute HCV infection wasfound to be minus HCV RNA positive. Though no HCV NS5protein expression was found in the examined 10 cases ofacute HCV infection, it was positive in 17 of 20 (85.0 %)chronic hepatitis C patients by indirect immunofluoresenceassay. There are significant differences of positive rate of theminus-strand and HCVNS5 protein between acute and chronichepatitis C groups(u=2.07, P<0.05and u=4.43, P<0.01respectively). The patients with minus-strand HCV RNAshowed a significantly lower 6-month sustained response (SR-6) to IFN compared to those without minus-strand HCVRNAin PBMCs (biologically 14.3 % vs 42.8 %, X2=4.12, P<0.05and virologically 7.1% vs23.9 %, X2=4.24, P<0.05).CONCLUSION: HCV is capable of infecting and replicatingin PBMCs, and HCVNS5 protein was expressed in PBMCs.The patients with minus strand HCV RNA in PBMCs showeda significantly lower 6-month sustained response to IFN,suggesting that minus-strand HCV RNA in PBMCs may beone of the factors influencing response to IFN therapy.

  5. Detection and analysis of HCV-RNA in banked blood%库血HCV-RNA的检测分析

    Institute of Scientific and Technical Information of China (English)

    姚萍; 伍继新; 胡兆平; 陶良军; 叶冬青; 黄芬

    2001-01-01

    目的为探索提高库血丙型肝炎病毒(HCV)的检出率.方法采用逆转录套式聚合酶链反应(RT-PCR)技术,检测4 530份抗-HCV阴性的库血HCV-RNA.结果 4 530份库血中HCV-RNA阳性55份,阳性率1.21%,其中个体献血者血液2 110份,HCV-RNA阳性40份,阳性率1.90%;无偿献血者血液2 420份,HCV-RNA阳性15份,阳性率0.62%.结论 RT-PCR可用于检测库血HCV-RNA,以减少因输血造成HCV感染.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. HCV抗原、HCV抗体及HCV-RNA联合检测与ALT的相关性分析%HCV antigen and antibody of HCV and HCV-RNA joint detection and correlation analysis of ALT

    Institute of Scientific and Technical Information of China (English)

    周珍娟

    2016-01-01

    目的 探究分析HCV抗原、HCV抗体及HCV-RNA联合检测与ALT的相关性.方法 随机选取我院在2013年2月-2015年2月期间接收的120例HCV-RNA阳性丙肝患者,采用不同的方法分别检查患者丙氨酸氨基转移酶(ALT)的含量水平、HCV抗原(HCV-cAg)、HCV抗体(HCV-Ab)以及HCV-RNA,并对所有数据进行统计分析.结果 120例HCV-RNA阳性丙肝患者中HCV抗原的阳性率为80.0%,HCV抗体的阳性率为95.0%,ALT含量的变化和HCV-RNA载体含量之间没有明显的相关性(P>0.05),HCV-RNA载体含量越高,则HCV抗体的阳性率越高,HCV-RNA载体载体含量的升高会引起ALT异常率的升高,两者之间呈正相关(P<0.05).结论 对于HCV-RNA阳性丙肝患者中HCV抗原、HCV抗体及HCV-RNA联合检测可进一步明确丙肝病毒的感染力,对患者临床病情具有一定的评估作用,同时结合ALT可对患者治疗效果提供一定的参考,值得临床应用.

  11. Impact of interferon-ribavirin treatment on hepatitis C virus (HCV) protease quasispecies diversity in HIV- and HCV-coinfected patients

    Science.gov (United States)

    Chary, Aarthi; Winters, Mark A.; Kottilil, Shyam; Murphy, Alison A.; Polis, Michael A.; Holodniy, Mark

    2010-01-01

    Patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection for whom prior treatment of HCV with interferon-ribavirin has failed may require subsequent treatment with new HCV protease inhibitors (PIs). We evaluated the diversity of HCV nonstructural protein 3 (NS3) in 26 HCV- and HIV-coinfected patients receiving stable antiretroviral therapy (ART) who were treated with interferon-ribavirin. Plasma HCV RNA clonal analysis was performed. There was greater baseline NS3 diversity in patients with nonresponse or relapse than in those with sustained virologic response. Interferon-ribavirin treatment did not result in significant changes in HCV protease gene diversity or significant HCV PI resistance mutations. The effect of prior interferon-ribavirin treatment on HCV NS3 will likely not impact HCV PI efficacy in HIV-coinfected patients receiving ART. PMID:20677940

  12. 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.

  13. 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

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

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    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.

  15. HCV-RNA positivity in peripheral blood mononuclear cells of patients with chronic HCV-infection: does it really mean viral replication?

    Institute of Scientific and Technical Information of China (English)

    Volker Meier; Sabine Mihm; Perdita Wietzke-Braun; Guliano Ramadori

    2001-01-01

    AIM To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC)and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication,METHODS HCV-RNA was monitored in serumand PBMC preparations from 15 patients with chronic HCV infection before, during and after an IFN-α therapy using a nested RT/ PCRtechnique. In a second approach, PBMC from healthy donors were incubated in HCV positive plasma.RESULTS In the IFN-α responding patients,HCV-RNA disappeared first from total RNApreparations of PBMC and then from serum. In contrast, in relapsing patients, HCV-RNAreappeared first in serum and then in PBMC. A quantitative analysis of the HCV-RNAconcentration in serum was performed before and after transition from detectable to nondetectable HCV-RNA in PBMC-RNA and vice versa. When HCV-RNA was detectable in PBMCpreparations, the HCV concentration in serum was significantly higher than the serum HCV-RNA concentration when HCV-RNA in PBMC was not detectable. Furthermore, at no time during the observation period was HCV specific RNA observed in PBMC, if HCV-RNA in serum was under the detection limit. Incubation of PBMCfrom healthy donors with several dilutions of HCV positive plasma for two hours showed a concentration-dependent PCR-positivity for HCV-RNA in reisolated PBMC.CONCLUSION The detectability of HCV-RNA in total RNA from PBMC seems to depend on the HCV concentration in serum. Contamination or passive adsorption by circulating virus could be the reason for detection of HCV-RNA in PBMCpreparations of chronically infected patients.

  16. 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).

  17. Lymphocytes and liver fibrosis in HIV & HCV coinfection

    NARCIS (Netherlands)

    Feuth, M.

    2014-01-01

    Coinfection with HIV has an important impact on immunity against hepatitis C virus (HCV). In the present dissertation, phenotypes of lymphocytes derived from the peripheral blood of HCV-infected patients were studied into detail, with special attention to changes in phenotype of lymphocytes associat

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

    DEFF Research Database (Denmark)

    Omland, Lars Haukali; 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....

  19. 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. PMID:27313634

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

    Directory of Open Access Journals (Sweden)

    Onyekwere

    2016-05-01

    Full Text Available 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.

  1. HCV-Induced Oxidative Stress: Battlefield-Winning Strategy

    Science.gov (United States)

    Rebbani, Khadija; Tsukiyama-Kohara, Kyoko

    2016-01-01

    About 150 million people worldwide are chronically infected with hepatitis C virus (HCV). The persistence of the infection is controlled by several mechanisms including the induction of oxidative stress. HCV relies on this strategy to redirect lipid metabolism machinery and escape immune response. The 3β-hydroxysterol Δ24-reductase (DHCR24) is one of the newly discovered host markers of oxidative stress. This protein, as HCV-induced oxidative stress responsive protein, may play a critical role in the pathogenesis of HCV chronic infection and associated liver diseases, when aberrantly expressed. The sustained expression of DHCR24 in response to HCV-induced oxidative stress results in suppression of nuclear p53 activity by blocking its acetylation and increasing its interaction with MDM2 in the cytoplasm leading to its degradation, which may induce hepatocarcinogenesis. PMID:27293514

  2. 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...... through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic...... countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity...

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

    Directory of Open Access Journals (Sweden)

    Scheinmann Roberta

    2008-09-01

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

  4. May some HCV genotype 1 patients still benefit from dual therapy? The role of very early HCV kinetics.

    Science.gov (United States)

    Tontodonati, Monica; Cento, Valeria; Polilli, Ennio; Colabattista, Cecilia; Cascella, Raffaella; Sciotti, Mariapina; Di Giammartino, Dante; Trave, Francesca; Di Maio, Velia Chiara; Monarca, Roberto; Di Candilo, Francesco; Prinapori, Roberta; Rastrelli, Elena; Vecchiet, Jacopo; Ceccherini-Silberstein, Francesca; Manzoli, Lamberto; Giardina, Emiliano; Perno, Carlo Federico; Parruti, Giustino

    2015-10-01

    When treating HCV patients with conventional dual therapy in the current context of rapidly evolving HCV therapy, outcome prediction is crucial and HCV kinetics, as early as 48 hours after the start of treatment, may play a major role. We aimed at clarifying the role of HCV very early kinetics. We consecutively enrolled mono-infected HCV patients at 7 treatment sites in Central Italy and evaluated the predictive value of logarithmic decay of HCV RNA 48 hours after the start of dual therapy (Delta48). Among the 171 enrolled patients, 144 were evaluable for early and sustained virological response (EVR, SVR) prediction; 108 (75.0%) reached EVR and 84 (58.3%) reached SVR. Mean Delta 48 was 1.68 ± 1.22 log10 IU/ml, being higher in patients with SVR and EVR. Those genotype-1 patients experiencing a Delta 48 >2 logs showed a very high chance of success (100% positive predictive value), even in the absence of rapid virological response (RVR). Evaluation of very early HCV kinetics helped identify a small but significant proportion of genotype-1 patients (close to 10%) in addition to those identified with RVR, who could be treated with dual therapy in spite of not reaching RVR. In the current European context, whereby sustainability of HCV therapy is a crucial issue, conventional dual therapy may still play a reasonable role in patients with good tolerance and early prediction of success.

  5. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Rehman Irshad U

    2011-07-01

    Full Text Available 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 was digested with proper restriction enzymes to release the target gene which was then inserted downstream of GST encoding DNA in the same open reading frame at proper restriction sites in multiple cloning site of pGEX4t2 expression vector. Recombinant expression vector for each gene was transformed in E. coli BL21 (DE3 and induced with IPTG for recombinant fusion protein production that was then purified through affinity chromatography. Western blot and Enzyme Linked Immunosorbant Assay (ELISA were used to detect immuno-reactivity of the recombinant protein. Results The HCV core antigen produced in prokaryotic expression system was reactive and used to develop a screening assay. After validating the positivity (100% and negativity (100% of in-house anti-HCV screening assay through a standardized panel of 200 HCV positive and 200 HCV negative sera, a group of 120 serum specimens of suspected HCV infection were subjected to comparative analysis of our method with commercially available assay. The comparison confirmed that our method is more specific than the commercially available assays for HCV strains circulating in this specific geographical region of the world and could thus be used for HCV screening in Pakistan. Conclusion In this study, we devised a screening assay after successful PCR amplification, isolation, sequencing, expression and purification of core antigen of HCV genotype 3a. Our developed screening assay is more sensitive, specific and

  8. High dead-space syringes and the risk of HIV and HCV infection among injecting drug users.

    Science.gov (United States)

    Zule, William A; Bobashev, Georgiy

    2009-03-01

    This study examines the association between using and sharing high dead-space syringes (HDSSs)--which retain over 1000 times more blood after rinsing than low dead-space syringes (LDSSs)--and prevalent HIV and hepatitis C virus (HCV) infections among injecting drug users (IDUs). A sample of 851 out-of-treatment IDUs was recruited in Raleigh-Durham, North Carolina, between 2003 and 2005. Participants were tested for HIV and HCV antibodies. Demographic, drug use, and injection practice data were collected via interviews. Data were analyzed using multiple logistic regression analysis. Participants had a mean age of 40 years and 74% are male, 63% are African American, 29% are non-Hispanic white, and 8% are of other race/ethnicity. Overall, 42% of participants had ever used an HDSS and 12% had shared one. HIV prevalence was 5% among IDUs who had never used an HDSS compared with 16% among IDUs who had shared one. The HIV model used a propensity score approach to adjust for differences between IDUs who had used an HDSS and those who had never used one. The HCV models included all potential confounders as covariates. A history of sharing HDSSs was associated with prevalent HIV (odds ratio=2.50; 95% confidence interval=1.01, 6.15). Use and sharing of HDSSs were also associated with increased odds of HCV infection. Prospective studies are needed to determine if sharing HDSSs is associated with increased HIV and HCV incidence among IDUs.

  9. HCV 抗原表位预测%Prediction of HCV antigenic epitopes

    Institute of Scientific and Technical Information of China (English)

    贾帅争; 孙红琰; 王全立

    2001-01-01

    应用网络生物信息资源查找丙型肝炎病毒基因组全序列,用软件Lasergene中的EditSeq将来自中国河北株mRNA序列翻译为氨基酸序列,尔后用程序Protean进行氨基酸序列分析,对HCV各区段的B细胞抗原指数进行预测。同时又在两个网站对中国汉族人中频率较高的HLA基因型进行CD8和CD4 T细胞表位预测。B细胞和T细胞抗原表位预测结果对于HCV诊断试剂和疫苗研制有重要的指导意义。%The complete genome of Hepatitis C China virus was gotten from world wide web site NCBI (National Center for Biotechnology Information). HCV mRNA was translated into amino acids(AA) sequence by program EditSeq of a computer software Lasergene and this amino acids sequence was analysed by program Protean. B cell epitopes index of these HCV AA fragments was caculated by this computational program and those epitopes with high index can be used as candidate epitopes for HCV antibody diagnositic reagent. CD8 T cell and CD4 T cell epitopes were predicted at Internet sites (SYFPEITHI and BIMAS). Because those HLA which appear with higher frequence in Chinese Nationalities were chosen to predict T cell epitopes, these predicted sequences can be used to design anti HCV vaccine suitable for Chinese.

  10. Antigenicity of the HCV HVR1 Peptide Analyzed by Computer Modeling

    Institute of Scientific and Technical Information of China (English)

    郑宇; 苏琴; 林芳; 赵军; 何卫平; 李伯安; 李静; 高蓉; 程云

    2003-01-01

    To find out the protective polypeptide epitopes of HCV HVR1, the antigenieity of the synthetic pepfide was predicted by computer modeling and verified by ELISA and lymphocyte transformation test. It was found that the outcome of the computer modeling was in accord with the experimental results. The method by using computer modeling would be a economic approach by which the protective peptides could be identified quickly.

  11. Maternal HCV infection is associated with intrauterine fetal growth disturbance

    Science.gov (United States)

    Huang, Qi-tao; Hang, Li-lin; Zhong, Mei; Gao, Yun-fei; Luo, Man-ling; Yu, Yan-hong

    2016-01-01

    Abstract Since the evidence regarding the association between maternal hepatitis C virus (HCV) infection and impaired intrauterine fetal growth had not been conclusive, the aim of the present study was to evaluate the risk of maternal HCV infection in association with intrauterine fetal growth restriction (IUGR) and/or low birth weight infants (LBW). We performed an extensive literature search of PubMed, MEDLINE, and EMBASE through December 1, 2015. The odds ratios (ORs) of HCV infection and IUGR/LBW were calculated and reported with 95% confidence intervals (95% CIs). Statistical analysis was performed using RevMen 5.3 and Stata 10.0. Seven studies involving 4,185,414 participants and 5094 HCV infection cases were included. Significant associations between HCV infection and IUGR (OR = 1.53, 95% CI: 1.40–1.68, fixed effect model) as well as LBW were observed (OR = 1.97, 95% CI: 1.43–2.71, random effect model). The results still indicated consistencies after adjusting for multiple risk factors which could affect fetal growth, including maternal age, parity, maternal smoking, alcohol abuse, drugs abuse, coinfected with HBV/HIV and preeclampsia. Our findings suggested that maternal HCV infection was significantly associated with an increased risk of impaired intrauterine fetal growth. In clinical practice, a closer monitoring of intrauterine fetal growth by a series of ultrasound might be necessary for HCV-infected pregnant population. PMID:27583932

  12. 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.

  13. 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

  14. The application of chemiluminescence in the detection of HCV/HIV%化学发光技术在HCV和HIV检测中的应用

    Institute of Scientific and Technical Information of China (English)

    李璐; 邢文革

    2011-01-01

    Various methods based on chemiluminescence for the detection of infections and course of diseases have been developed rapidly in the recent years, and are widely used in disease monitoring, screening and diagnosis. Technologies for the detection of HCV/HIV based on chemiluminescence have many advantages in comparison with other current technologies. Detection of HCV core antigen by chemiluminescence could result in not only a high sensitivity and specificity but also in a short window period; besides, by applying the linear relationship between the HCV RNA titers and the content of HCV core antigen in the samples, the HCV RNA titers are available. The sensitivity and specificity are both high and false positive rate is low when the chemiluminescence is used for detecting anti-HCV and anti-HIV. Chemiluminescence technology for testing the HCV/HIV nucleic can get a wide detection limit and linear range. In addition, the virus mutation and activity of reverse transcription can also be detected by the chemiluminescence technology. The chemiliminescence technology can be broadly used in detecting of HCV/HIV.%近年来利用化学发光技术检测疾病的感染状况及疾病进程的方法得到了迅速的发展,并在疾病的监测、筛查、诊断的方面得到了广泛应用.结合化学发光技术的丙型肝炎病毒(HCV)/艾滋病病毒(HIV)检测方法,具有很多优于现有检测手段的特点.化学发光技术用于检测HCV核心抗原不仅灵敏度、特异度高、窗口期短,而且可根据HCV核心抗原与RNA滴度间的线性关系,计算得出样本中的HCV RNA滴度;用于检测抗-HCV、抗-HIV检测时具有灵敏度高、特异度高、假阳性率低的优点.在HCV/HIV核酸检测方面,化学发光技术的检测限及线性范围更宽.此外,利用化学发光技术还可以对反转录酶活性及病毒的变异进行检测.化学发光技术在HCV/HIV的检测领域具有广泛的应用前景.

  15. 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.

  16. Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study.

    NARCIS (Netherlands)

    Miro, J.M.; Montejo, M.; Castells, L.; Rafecas, A.; Moreno, S.; Aguero, F.; Abradelo, M.; Miralles, P.; Torre-Cisneros, J.; Pedreira, J.D.; Cordero, E.; Rosa, G. De; Moyano, B.; Moreno, A.; Perez, I.; Rimola, A.; Barrera, P.

    2012-01-01

    Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty-six (43%) HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to

  17. ITPA Gene Polymorphisms Significantly Affect Hemoglobin Decline and Treatment Outcomes in Patients Coinfected With HIV and HCV

    Science.gov (United States)

    Osinusi, Anu; Naggie, Susanna; Poonia, Seerat; Trippler, Martin; Hu, Zonghui; Funk, Emily; Schlaak, Joerg; Fishbein, Dawn; Masur, Henry; Polis, Michael; Kottilil, Shyam

    2012-01-01

    Published studies have described a strong association with a single-nucleotide polymorphism (SNP) in the inosine triphosphate pyrophosphatase (ITPA) gene and ribavirin (RBV)-induced hemolytic anemia in HCV-infected patients receiving pegylated interferon (pegIFN) and RBV. This study sought to evaluate the effect of these polymorphisms on anemia, hemoglobin reduction, HCV kinetics, and treatment outcomes. Sixty-three patients coinfected with HIV and HCV and 58 patients infected with HCV only were treated with pegIFN/RBV were genotyped using the ABI Taq-Man allelic discrimination kit for the 2 ITPA SNP variants rs1127354 and rs7270101. A composite variable of ITPA deficiency using both SNPs was created as previously reported. Statistical analysis was performed using Mann-Whitney test or Chi square/Fishers exact test for categorical data and mixed model analysis for multiple variables. Thirty-five patients (30%) were predicted to have reduced ITPA activity. ITPA deficiency was found to be protective against the development of hemoglobin reduction >3 g/dl over the course of treatment. The rates of hemoglobin reduction >3 g/dl decreased in correlation with the severity of ITPA deficiency. ITPA deficiency was associated with slower hemoglobin decline early in treatment (week 4, P = 0.020) and rapid virologic response (RVR) at week 4 (P = 0.017) in patients coinfected with HIV and HCV. ITPA polymorphisms are associated with hemoglobin decline and in patients coinfected with HIV and HCV it is also associated with early virologic outcomes. Determination of ITPA polymorphisms may allow prediction of RBV-induced anemia and earlier initiation of supportive care to ensure optimal therapeutic outcomes. PMID:22585729

  18. HCV游离抗原BA-ELISA检测方法的临床应用评价%Evaluation on clinical application of HCV free antigen detection methods of BA-ELISA

    Institute of Scientific and Technical Information of China (English)

    龙润乡; 陈红英; 朱祥明; 沈云松; 孙翳; 苏品璨; 王俊; 谢忠平

    2013-01-01

    目的 根据国家相关法规对HCV游离抗原BA-ELISA检测方法进行临床应用效果评价.方法 生物素标记丙型肝炎病毒抗体(HCV-Ab)与辣根过氧化物酶标记亲和素联合应用建立HCV游离抗原BA-ELISA检测法,分别在3个省级医疗卫生机构进行临床试验,同时使用HCV-cAg、HCV-Ab、HCV-RNA荧光定量检测试剂盒进行对比同步检测.结果 临床试剂与HCV-Ab检测结果相比一致性66.67%,特异性100%;与荧光定量PCR相比结果一致性为80.85%、特异性为98.87%;同类市售产品HCV核心抗原检测试剂检测结果与之接近.结论 临床试剂特异性较好,灵敏度有待提高;临床研究试剂比市售同类产品阳性检出率略高,但两种试剂检出率均低于核酸及抗体检测试剂.%OBJECTIVE According to the national relative regulations, to evaluate effect of clinical application of HCV free antigen BA-ELISA detection method. METHODS Used biotin-labeled hepatitis C virus antibody (HCV-Ab) and horseradish peroxidase -conjugated avidin system to establish of free HCV antigen detection methods of BA-ELISA. Respectively in the three provincial-level medical and health institutions for clinical trials, meanwhile HCV-cAg, HCV-Ab, HCV-RNA fluorescence quantitative detection kit synchronous detection were compared. RESULTS Results of clinical study reagent compared with HCV-Ab test results, coincidence rate was 66.67%, specificity 100%; And compared with HCV-PCR, coincidence rate was 80.85%, specificity was 98.87%; The results were analogue by the commercial product HCV-Ag detection reagents and HCV-Ag detection reagents. CONCLUSION Better clinical study reagent specificity, sensitivity need to be improved; clinical study reagents than similar products commercially, positive rate is slightly higher, but both are lower than nucleic acid detection reagent and antibody detection kit.

  19. HCV prevalence and predominant genotype in IV drug users

    Directory of Open Access Journals (Sweden)

    Asad Andalibalshohada

    2014-07-01

    Full Text Available Hepatitis C virus (HCV causes 308000 deaths due to liver cancer and 758000 deaths due to cirrhosis every year. Almost 170 million people have HCV infection around the world. Information regarding this virus helps us to determine the prevalence of other hepatitis C genotypes in population, especially in intravenous drug users. It is assumed that some genotypes are more common in certain areas or groups of people. A recent study strongly confirms the central role of injecting network traits, not only as a transmission factor but also as a predictor of HCV genotype and phylogenetic determination in different communities. Hepatitis C genotypes and subtypes have different prevalence considering the country. Risk factors such as transfusion, hemodialysis, root of acquisition and etc, are detected in intravenous drug users. Several conducted studies have investigated the prevalence, risk factors, and predominance of HCV genotypes infection in different parts of Iran.

  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. 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.

  3. 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

  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. 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...

  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. Complementary Action of Combining Detection for HCV-cAg with HCV-Ab and the Relation Between HCV Positive Patients and ALT%HCV-cAg与HCV-Ab联合检测的互补作用及HCV阳性者与ALT的关系

    Institute of Scientific and Technical Information of China (English)

    陈小龙; 唐荣德; 华关民; 陈敏; 谭亮庆

    2014-01-01

    目的 探讨丙肝病毒核心抗原(HCV-cAg)与丙肝病毒抗体(HCV-Ab)联合检测对诊断丙肝病毒(HCV)感染的互补作用及HCV感染阳性者与丙氨酸氨基转移酶(ALT)的关系.方法 检测手术前检查组2061例患者和ALT>80 U/L组242例患者的HCV-cAg、HCV-Ab和ALT等指标,然后将检测结果作出统计分析.结果 手术前检查组联合检测有2.7%的阳性率,显著高于单独HCV-cAg和单独HCV-Ab的1.6%(P<0.05); ALT>80 U/L组联合检测有14.5%的阳性率,显著高于单独HCV-cAg的7.0%(P<0.01);手术前检查组ALT均值和ALT>80U/L例数是2项均阳性高于HCV-Ab阳性、HCV-Ab阳性高于HCV-cAg.结论 HCV-cAg和HCV-Ab 2项联合检测明显优于单项检测,这对HCV感染的诊断能起到很好的互补作用,加上ALT等肝功能指标的检测,有利于HCV感染的正确诊断.

  9. MicroRNA-122 antagonism against hepatitis C virus genotypes 1-6 and reduced efficacy by host RNA insertion or mutations in the HCV 5' UTR

    DEFF Research Database (Denmark)

    Li, Yiping; Gottwein, Judith; Scheel, Troels Kasper Høyer;

    2011-01-01

    MicroRNA-122 (miR-122) is believed to stimulate hepatitis C virus (HCV) replication through interaction with two adjacent sites downstream of stem loop I (SLI) within the HCV 5' untranslated region (5' UTR). Recently, it was demonstrated that locked nucleic acid SPC3649-induced miR-122 antagonism...... suppressed HCV genotype 1a and 1b infection in vivo. However, virus-producing culture systems with 5' UTR of different HCV genotypes have not been available for testing 5' UTR-based treatment approaches. Using JFH1-based Core-NS2 genotype recombinants, we developed 5' UTR-NS2 recombinants of HCV genotypes 1a......, 1b, 2a, 2b, 3a, 4a, 5a, and 6a with efficient growth in Huh7.5 cells. Deletion mutagenesis studies demonstrated that the 5' UTR SLI was essential for genotypes 1-6 infection. However, lack of SLI could be compensated for by insertion of other structured HCV or host RNA sequences, including U3 small...

  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. Legalon-SIL downregulates HCV core and NS5A in human hepatocytes expressing full-length HCV

    Institute of Scientific and Technical Information of China (English)

    Marjan Mehrab-Mohseni; Hossein Sendi; Nury Steuerwald; Sriparna Ghosh; Laura W Schrum; Herbert L Bonkovsky

    2011-01-01

    AIM: To determine the effect of Legalon-SIL (LS) on hepatitis C virus (HCV) core and NS5A expression and on heme oxygenase-1 (HMOX-1) and its transcriptionalregulators in human hepatoma cells expressing full length HCV genotype 1b.METHODS: CON1 cells were treated with 50 μmol/or 200 μmol/L LS. Cells were harvested after 2, 6 and 24 h. HCV RNA and protein levels were determined byquantitative real-time polymerase chain reaction and Western blotting, respectively.RESULTS: HCV RNA (core and NS5A regions) was decreased after 6 h with LS 200 μmol/L (P < 0.05).Both 50 and 200 μmol/L LS decreased HCV RNA levels[core region (by 55% and 88%, respectively) and NS5A region (by 62% and 87%, respectively) after 24 h compared with vehicle (dimethyl sulphoxide) control (P< 0.01). Similarly HCV core and NS5A protein were decreased(by 85%, P < 0.01 and by 65%, P < 0.05, respectively)by LS 200 μmol/L. Bach1 and HMOX-1 RNAwere also downregulated by LS treatment (P < 0.01),while Nrf2 protein was increased (P < 0.05).CONCLUSION: Our results demonstrate that treatment with LS downregulates HCV core and NS5A expression in CON1 cells which express full length HCVgenotype 1b, and suggests that LS may prove to be a valuable alternative or adjunctive therapy for the treatment of HCV infection.

  13. Comprehensive longitudinal analysis of hepatitis C virus (HCV)-specific T cell responses during acute HCV infection in the presence of existing HIV-1 infection

    NARCIS (Netherlands)

    C.H.S.B. van den Berg; T.A. Ruys; N.M. Nanlohy; S.E. Geerlings; J.T. van der Meer; J.W. Mulder; J.A. Lange; D. van Baarle

    2009-01-01

    The aim of this study was to study the development of HCV-specific T cell immunity during acute HCV infection in the presence of an existing HIV-1 infection in four HIV-1 infected men having sex with men. A comprehensive analysis of HCV-specific T cell responses was performed at two time points duri

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  16. 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

  17. Clinical significance of joint detection of HCV antigen, HCV antibody and HCV RNA, and its correlation analysis with ALT%HCV抗原、HCV抗体及HCV-RNA联合检测与ALT的相关性及其临床意义

    Institute of Scientific and Technical Information of China (English)

    邵芳

    2014-01-01

    [目的]探讨HCV-RNA阳性丙肝患者核心抗原(HCV-cAg)、抗体(HCV-Ab)以及HCV-RNA含量3种检测指标与丙氨酸氨基转移酶(ALT)水平的相关性及其临床意义.[方法]对100例HCV-RNA阳性丙肝患者应用酶速率法检测ALT含量、ELISA法检测HCV-cAg、CLIA法检测HCV-Ab、FQ-PCR法检测HCV-RNA,并对所得数据进行统计分析.[结果[100例患者血清中HCV-Ab阳性率为97.0%,HCV-cAg阳性率为83.0%;HCV-RNA载体含量越高,HCV-Ab阳性率越高;ALT含量的变化与HCV-RNA载体含量并无明显相关性(P>0.05);ALT异常率随着HCV-RNA含量的增高而升高,呈正相关(P<0.05).[结论]HCV-Ab检测可反映机体对HCV感染的免疫状态,能间接证实HCV感染;HCV-RNA敏感性和特异性较高,HCV-RNA与HCV-cAg阳性检出率呈现一致性,且ALT异常率随着HCV-RNA含量的增高而升高,可以反映临床病情;3种方法同时检测能准确诊断丙肝病毒的感染,以及预测是否具有传染性,联合ALT可有效预测和评价肝脏损伤和药物疗效.

  18. Proteome-wide Anti-HCV and Anti-HIV Antibody Profiling for Predicting and Monitoring Response to HCV Treatment in HIV Co-infected Patients

    Science.gov (United States)

    Burbelo, Peter D.; Kovacs, Joseph A.; Ching, Kathryn H.; Issa, Alexandra T.; Iadarola, Michael J.; Murphy, Alison A; Schlaak, Joerg F.; Masur, Henry; Polis, Michael A.; Kottilil, Shyam

    2010-01-01

    We quantified antibody responses to the HCV proteome that are associated with sustained virologic response (SVR) in HIV/HCV co-infected patients treated with pegylated interferon and ribavirin. Analysis of pre- and post-treatment samples revealed significant decreases in the combined anti-core, anti-E1 and anti-NS4 HCV antibody titers in those with SVR, but not in the relapsers or non-responders. Furthermore, anti-p24 HIV antibody titers inversely correlated with treatment response. These results suggest that profiling anti-HCV antibody is useful for monitoring HCV therapy especially in discriminating between relapsers and SVRs at 48 weeks. PMID:20684729

  19. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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

  2. 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...

  3. CLIA(抗-HCV)联合EIA(HCV-cAg)在HCV感染初筛试验中的意义

    Institute of Scientific and Technical Information of China (English)

    黄建梅

    2016-01-01

    目的 分析CLIA(抗-HCV)联合EIA(HCV-cAg)在HCV感染初筛试验中的意义.方法 选取56例住院患者,检测丙肝抗体和丙肝核心抗原,对HCV感染初筛阳性患者均采取抗-HCV和HCV-cAg检测.结果 CLIA和EIA检测阳性患者ALI水平大于40 U/L,阳性率差异不明显,P>0.05,抗-HCV/CLIA(+)+HCV-cAg(-)阳性率(98.1%)显著高于抗HCV/EIA(+)+HCV-cAg(-)(94.7%),P<0.05,HCV/CLIA(+)+HCV-cAg(+)阳性患者CLIA阳性率(98.6%)显著高于EIA(85.7%),P<0.05.结论 在HCV感染初筛试验中,CLIA(抗-HCV)联合EIA(HCV-cAg)检出率高,阳性符合率更高.

  4. Gene Expression Profiles Predict Emergence Of Psychiatric Adverse Events In HIV/HCV Coinfected Patients On Interferon-based HCV Therapy

    Science.gov (United States)

    Rasimas, J.J; Katsounas, A; Raza, H; Murphy, A.A; Yang, J; Lempicki, R.A; Osinusi, A; Masur, H; Polis, M.A; Kottilil, S; Rosenstein, D.L

    2012-01-01

    Background The efficacy of pegylated IFN-α and ribavirin (pegIFN/RBV) in the treatment of Hepatitis C infection is limited by psychiatric adverse effects (IFN-PE). Our study examined the ability of differential gene expression patterns prior to therapy to predict emergent IFN-PE among 28 HIV/HCV co-infected patients treated with pegIFN-α2b/RBV. Methods Patients dually infected with HIV and HCV were evaluated at baseline and during treatment by board-certified psychiatrists who classified patients into 2 groups: those who developed IFN-PE and those who did not (IFN-NPE). Gene expression analysis (Affymetrix HG-U133A) was performed using PBMCs before and after initiation of treatment. ANOVA, post hoc analysis based on pair-wise comparisons and functional annotation analysis identified differentially expressed genes within and between groups. Prediction Analysis for Microarrays was used to test the predictive ability of selected genes. Results Twenty-four genes (16 up- and 8 down-regulated) that were differentially expressed at baseline in patients who subsequently developed IFN-PE compared to the IFN-NPE group showed the ability to predict IFN-PE with an accuracy of 82%. In 16 patients with IFN-PE, 135 genes (117 up-; 18 down-regulated) were significantly modulated following treatment. Of these, 10 genes have already been shown to be associated with neuropsychiatric illnesses and were significantly modulated only in patients who experienced IFN-PE. Conclusions We describe a novel molecular diagnostic biomarker panel to predict emergent IFN-PE in HIV/HCV-co-infected patients undergoing pegIFN/RBV treatment, which may improve the identification of patients at greatest risk for IFN-PE and suggest candidate therapeutic targets for preventing or treating IFN-PE. PMID:22728749

  5. [HCV and HBV prevalence in hemodialyzed pediatric patients. Multicenter study].

    Science.gov (United States)

    Cañero-Velasco, M C; Mutti, J E; Gonzalez, J E; Alonso, A; Otegui, L; Adragna, M; Antonuccio, M; Laso, M; Montenegro, M; Repetto, L; Brandi, M; Canepa, J; Baimberg, E

    1998-01-01

    Hemodialized pediatric patients are a risk population for the hepatitis B and C virus infection. The aim of this paper was to study the serum prevalence of HBV and HCV infection in hemodialized children. We study 61 pediatric patients at hemodialisis, 12 on renal transplant, range between 2 and 20 years old (mean: 12.9 years), 23 male and 38 female. The specific anti-HCV IgC were measured by enzyme immunoassay (ELISA Abbott) and confirmed by LIA-TEK (Organon). The anti-HBV were measured by ELISA Abbott and transaminases by cinetic method (ASAT: 29 UI/L and ALT: 33 UI/L). The 19.7% of studied children were HCV (+) and 29.5% were HBV (+), 38.9% of them were HbsAg (+) and 50% anti-HBs (+). The HCV and HBV infection was more elevated in relation to the transfusion number and the hemodilisis time. The elevation of ALT/ASAT activity isn't a right infection index for HCV and HBV in this children. PMID:9773156

  6. Simultaneous detection of HBV and HCV by multiplex PCR normalization

    Institute of Scientific and Technical Information of China (English)

    Ning Wang; Xue-Qin Gao; Jin-Xiang Han

    2004-01-01

    AIM: To design and establish a method of multiplex PCR normalization for simultaneously detecting HBV and HCV.METHODS: Two pairs of primers with a 20 bp joint sequence were used to amplify the target genes of HBV and HCV by two rounds of amplification. After the two rounds of amplification all the products had the joint sequence. Then the joint sequence was used as primers to finish the last amplification. Finally multiplex PCR was normalized to a single PCR system to eliminate multiplex factor interference. Four kinds of nucleic acid extraction methods were compared and screened. A multiplex PCR normalization method was established and optimized by orthogonal design of 6 key factors. Then twenty serum samples were detected to evaluate the validity and authenticity of this method.RESULTS: The sensitivity, specificity, diagnostic index and efficiency were 83.3%, 70%, 153.3% and 72.2%,respectively for both HBsAg and anti-HCV positive patients,and were 78.6%, 80%, 258.6% and 79.2%, respectively for HBsAg positive patients, and were 75%, 90%, 165%and 83.3%, respectively for anti-HCV positive patients.CONCLUSION: The multiplex PCR normalization method shows a broad prospect in simultaneous amplification of multiple genes of different sources. It is practical, correct and authentic, and can be used to prevent and control HBV and HCV.

  7. ELISA试剂检测抗HCV反应性结果分析%Result analysis on anti-HCV reaction determination by ELISA reagents

    Institute of Scientific and Technical Information of China (English)

    傅立强; 桑列勇; 蒋国瑾

    2012-01-01

    Objective To evaluate the efficiency of imported anti-hepatitis C virus ( HCV) enzyme-linked immunosorbent assay ( ELISA) reagent in blood screening test and analyze the correlations among imported ELISA reagent, domestic ELISA reagent and recombinant immunoblot assay(RIBA). Methods A total of 56 anti-HCV positive specimens tested by imported ELISA reagent were retested by 2 domestic ELISA reagents, and the confirmatory test RIBA was also carried out. Results Among 56 positive specimens with imported anti-HCV ELISA reagent, the confirmatory test RIBA showed that the 12 specimens were confirmed to be positive ,18 specimens were indeterminate and 26 specimens were negative. Of the 9 specimens which were positive with 3 ELISA reagents, 7 specimens were confirmed to be positive, 1 specimen was indeterminate and 1 specimen was negative. Conclusions The false positivity with anti-HCV ELISA reagent is obvious, and there would be some different results with different anti-HCV ELISA reagents. For ensuring the blood safety, the imported ELISA reagent and the domestic ELISA reagent shpuld be used simultaneously in anti-HCV screening test.%目的 探讨丙型肝炎病毒抗体(抗HCV)进口酶联免疫吸附试验(ELISA)试剂在血液筛查中的效果及与国产试剂、重组免疫印迹试验(RIBA)确证检测的相关性.方法 用RIBA确证试剂及国内销量前2名的国产抗HCV ELISA试剂对56例进口抗HCV ELISA试剂检测呈反应性的标本进行检测分析.结果 56例标本经RIBA确证结果为阳性12例,不确定18例,阴性26例.3种试剂均为反应性的9例标本中,确证阳性7例,不确定1例,阴性1例.结论 目前市售的丙型肝炎ELISA试剂均存在较大的生物学假阳性,不同试剂间检测结果仍存在一定差异.为确保输血安全,建议有条件的采供血机构实验室抗HCV检测时以国产和进口试剂联合检测为佳.

  8. Detection and genotyping of HCV RNA in anti-HCV positive serum%抗-HCV阳性血清HCV RNA检测与基因分型的研究

    Institute of Scientific and Technical Information of China (English)

    谢晨; 解莹; 冯继红; 金萍

    2009-01-01

    Objective To detect and do genotyping of HCV RNA in anti-HCV positive serum.Methods HCV RNA was detected by fluorescent quantitation PCR in anti-HCV positive serum of 85 cases in Dalian area,and genotype was detected by type specificity primer reverse transcription nest PCR in HCV RNA positive specimens.Results In 85 cases of anti-HCV positive specimens,there were 65 cases of HCV RNA positive(76.5%).In the HCV RNA positive serum,there were 32 cases of 1b genotype(49.2%),29 cases of 2a genotype(44.6%),4 cases of the others(6.2%).Conclusions Anti-HCV positive is not direct mark for hepatitis C diagnosis,quantity of lb genotype is nearly equal to 2a genotype of hepatitis C virus in Dalian area.%目的 检测抗-HCV阳件血清巾的HCV RNA并进行HCV基因分型.方法 采用荧光定量PCR法检测85例大连地区抗-HCV阳性患者血清中HCV RNA,应用型特异性引物逆转录套式PCR法对HCV RNA阳性样本进行基因分型.结果 85例的抗-HCV阳性患者中,HCV RNA阳性65例(76.5%),其中基因分型1b型32例(49.2%),2a型29例(44.6%),未分型4例(6.2%).结论 抗-HCV阳性并非HCV直接标志,大连地区HCV基冈1b型和2a型基本相等.

  9. Value of two noninvasive methods to detect progression of fibrosis among HCV carriers with normal aminotransferases.

    Science.gov (United States)

    Colletta, Cosimo; Smirne, Carlo; Fabris, Carlo; Toniutto, Pierluigi; Rapetti, Rachele; Minisini, Rosalba; Pirisi, Mario

    2005-10-01

    The course of hepatitis C virus (HCV) infection carriers with normal/near-normal aminotransferases (NALT) is usually mild; however, in a few, fibrosis progression occurs. We aimed to verify whether monitoring by liver biopsy might be replaced by noninvasive methods and to identify factors associated with fibrosis progression in patients with persistently normal alanine aminotransferases. We studied 40 untreated HCV-RNA-positive subjects (22 male; median age, 44 years), who underwent two liver biopsies, with a median interval of 78.5 months, during which alanine aminotransferase concentrations (median number of determinations: 12) never exceeded 1.2 times the upper normal limit. Within 9 months from the second biopsy, they were tested by the shear elasticity probe (Fibroscan) and the artificial intelligence algorithm FibroTest. METAVIR fibrosis scores were analyzed in relationship to demographic, clinical, and viral parameters. Weighted kappa analysis was used to verify whether the results of noninvasive methods agreed with histology. Significant fibrosis (> or = F2), present at the first biopsy in only one patient (2.5%), was observed at the second biopsy in 14 patients (35%). At multivariate analysis, excess alcohol consumption in the past (>20 g/d; P = .017) and viral load (>8.0 x 10(6) copies/mL; P = .021) were independent predictors of progression. In identifying patients with significant fibrosis, inter-rater agreement was excellent for Fibroscan (weighted kappa = 1.0), and poor for FibroTest (weighted kappa = -0.041). In conclusion, among HCV carriers with NALT, Fibroscan is superior to the FibroTest in the noninvasive identification of fibrosis, for which excess alcohol consumption in the past and high viral load represent risk factors.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  12. 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

  13. HIV and HCV Medications in End-Stage Renal Disease.

    Science.gov (United States)

    Greenberg, Keiko I; Perazella, Mark A; Atta, Mohamed G

    2015-01-01

    Human immunodeficiency virus (HIV) infection and hepatitis C virus (HCV) infection affect populations worldwide. With the availability of over 35 Food and Drug Administration approved medications for treatment of HIV, the morbidity and mortality associated with HIV has greatly improved. On the other hand, treatment options for HCV have been limited until very recently. While the use of protease inhibitors (such as boceprevir and telaprevir) has become standard of care for treatment of hepatitis C in the general population, data for individuals with impaired kidney function, particularly those on dialysis, are extremely limited. Use of medications in dialysis patients can be challenging given the dose adjustments that must be made for renally cleared molecules, and potentially increased impact of adverse effects such as anemia. Recommendations for dosing of marketed therapies for HIV and HCV are reviewed.

  14. [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

  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 (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs...... when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However...

  16. 献血者HCV检测模式的初步探讨%Evaluation of HCV screening strategy in blood donors

    Institute of Scientific and Technical Information of China (English)

    张磊; 王卓妍; 龚晓燕; 宋美兰; 任芙蓉

    2013-01-01

    目的 探讨核酸扩增技术(NAT)检测后进行一次酶联免疫吸附试验(ELISA)检测的可能风险.方法 收集双试剂(金伟凯及Ortho)HCV ELISA筛查判为不合格的献血者血液291份,进行核酸检测及血清学确证试验.分析单试剂检测漏检的情况.结果 选用金伟觊anti-HCV ELISA作为单次ELISA检测,291份不合格血标本中97份被判为ELISA检测合格(S/CO<0.7)同时NAT检测合格,其中3份(1.0%)重组免疫印迹(RIBA)确证试验阳性的血液被NAT和ELISA漏检;选用Ortho anti-HCV ELISA作为单次ELISA检测.291份不合格血标本中88份被判为ELISA检测合格(S/CO<0.7)同时NAT检测合格,其中2份(0.7%)RIBA确证试验阳性的血液被漏检.结论 NAT检测后去掉两次ELISA检测中的一次检测模式暂时尚需慎重,需加大样本量迸一步分析研究.%Objective To determine if nucleic acid tests (NAT) can effectively detect the unqualified blood which is positive by single HCV enzyme linked immunosorbent assay (ELISA) reagent and confirmed by recombinant immunoblot assay(RIBA) confirmation test, and study the possible risk of delete one of the two rounds of HCV ELISA screening. Methods 291 unqualified blood samples, which were screened by two different anti-HCV ELISA kits GWK and Ortho, were collected. Samples were further tested by NAT and RIBA. The false negative risk by single ELISA kit was analyzed. Results If specimens were only tested by GWK anti-HCV ELISA kits, 97 of 291 anti-HCV unqualified samples were negative (S/CO<0.7) by anti-HCV ELISA and NAT, and among which, 3 samples (3/291, 1.0%) which were positive confirmed by RIBA would be missed. If specimens were only tested by Ortho anti-HCV ELISA kits, 88 of 291 anti-HCV unqualified samples were negative (S/CO<0.7) by anti-HCV ELISA and NAT, and among which, 2 samples (2/291, 0.7%) which were confirmed to be positive by RIBA would be missed. Conclusion It indicates that after the implementation of NAT, it

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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

  20. 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...

  1. 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

  2. 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.

  3. Impaired hepatosplenic elimination of circulating cryoglobulins in patients with essential mixed cryoglobulinaemia and hepatitis C virus (HCV) infection

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    ROCCATELLO, D; MORSICA, G; PICCIOTTO, G; CESANO, G; ROPOLO, R; BERNARDI, M T; CACACE, G; CAVALLI, G; SENA, L M; LAZZARIN, A; PICCOLI, G; RIFAI, A

    1997-01-01

    The pathogenic mechanisms that lead to renal deposition of the cryoprecipitable IgM rheumatoid factor–IgG complexes in essential mixed cryoglobulinaemia (EMC) are unknown. Defective removal of cryoprecipitable complexes from the circulation has been postulated in EMC-associated nephritis. To test this hypothesis, the kinetics and fate of a trace dose of 123I-radiolabelled autologous cryoglobulins were analysed in 13 patients with EMC grouped according to renal involvement. The time course of radioactivity distribution in the blood and organ uptake were measured by gamma camera scintigraphy. In blood sampled 30–300 s after injection, only a minor fraction ( 4 h) biphasic pattern. In patients with quiescent or mild nepthritis, the liver and to a lesser extent the spleen were the major organs that mediated the rapid uptake and processing of the cryoglobulins from the circulation. In contrast, patients with active mesangiocapillary glomerulonephritis showed significantly (P< 0.001) less hepatic uptake, low liver-to-precordium ratio, and slower processing of cryoglobulins, prolonged liver mean transit time, than quiescent patients or mild nephritis patients. To elucidate the role and influence of HCV infection in the pathogenesis of EMC-nephritis, sera and cryoglobulins from all patients were assayed for HCV. None of the control group cases without nephritis showed any evidence of HCV-RNA in serum or cryoglobulin pellet. In contrast, all 10 EMC-nephritis patients' sera, and eight corresponding cryoglobulin pellets contained HCV-RNA. Collectively, these findings suggest an impaired reticuloendothelial system removal of IgM–IgG–HCV complexes may underlie their renal deposition. PMID:9353142

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

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    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 ...

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

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    Chris R. Kenyon

    2014-01-01

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

  6. 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.

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

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    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

  8. HCV Proteins and Immunoglobulin Variable Gene (IgV Subfamilies in HCV-Induced Type II Mixed Cryoglobulinemia: A Concurrent Pathogenetic Role

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    Giuseppe Sautto

    2012-01-01

    Full Text Available The association between hepatitis C virus (HCV infection and type II mixed cryoglobulinemia (MCII is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV gene subfamilies frequently endowed with rheumatoid factor (RF activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved.

  9. [Control of HCV, HBV and HIV Infections in Hemodialysis].

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    Fabrizi, Fabrizio; Martin, Paul; Messa, Piergiorgio

    2013-01-01

    Infections with blood-borne pathogens are still common among patients on maintenance dialysis all over the world. The control of infection due to blood-borne viruses (particularly HBV) within dialysis units has been a major goal in the management of patients with chronic kidney disease in the industrialized world. Standard precautions and specific procedures have been recommended to prevent infections with HBV, HCV and HIV within dialysis units. Isolation of HBsAg positive patients by dialysis rooms, staff and machines continues to be an important step to control HBV infection within dialysis units, according to the CDC and other regulatory agencies. Some prospective observational studies have reported the complete prevention of HCV transmission to hemodialysis patients in the absence of any isolation policy, and the use of dedicated dialysis machines for HCV-infected patients is not recommended by clinical guidelines. Isolation of HCV-infected patients should be considered in special circumstances only. Vaccination is an important tool against transmission of HBV among patients on long-term dialysis even if the immune response towards the hepatitis B vaccine remains unsatisfactory. Hemodialysis is considered a low risk setting for the transmission of human immunodeficiency virus (HIV) infection, providing that standard and specific procedures are carefully observed. HIV-infected patients do not have to be isolated from other patients or dialyzed separately on dedicated machines.

  10. Prevalence of hepatitis C virus (HCV) genotypes in Balochistan.

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    Afridi, Sarwat; Naeem, Muhammad; Hussain, Abid; Kakar, Naseebullah; Babar, Masroor Ellahi; Ahmad, Jamil

    2009-07-01

    A molecular study was conducted to investigate the prevalence of Hepatitis C virus genotypes in HCV infected population of Balochistan. Forty HCV seropositive samples belonging to seven different locations of Balochistan were collected from different health care centres. Qualitative analysis of these samples using PCR resulted in 28 positive samples. The PCR positive samples were subjected to genotyping using the method described by Ohno et al (J Clin Microbiol 35:201-202, 1997) with minor modifications. Genotyping of 28 samples revealed three different genotypes including 3a, 3b and 1a. The most prevalent genotype was 3a with rate of 50% followed by genotype 3b and 1a, respectively. Nine samples remained untyped, suggesting the need of further investigation of genotypes in this region. It has been proposed that sequencing of these samples may be helpful to unreveal these genotypes and further epidemiology of HCV genotypes. Further more, extensive and large scale studies are needed to understand the epidemiology of HCV genotypes, as no such study has been carried in this province.

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

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    Michele Barone

    2015-01-01

    Full Text Available 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.

  12. 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.

  13. Discovery of Novel Small Molecule Anti-HCV Agents via the CypA Inhibitory Mechanism Using O-Acylation-Directed Lead Optimization

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    Wenzhong Yan

    2015-06-01

    Full Text Available In this work, the relationship between cyclophilin A (CypA and HCV prompted us to screen a series of small molecule CypA inhibitors which were previously reported by our group. Among them, compound 1, discovered as a non-immunosuppressive anti-HCV agent with an EC50 value of 0.67 μM in a virus assay, was selected for further study. Subsequent chemical modification by O-acylation led to a novel class of molecules, among which compound 25 demonstrated the most potent anti-HCV activity in the virus assay (EC50 = 0.19 μM, but low cytotoxicity and hERG cardiac toxicity. The following studies (a solution stability assay and a simple pharmacokinetic test together with a CypA enzyme inhibition assay preliminarily indicated that 25 was a prodrug of 1. To the best of our knowledge, 25 is probably the most potent currently reported small molecule anti-HCV agent acting via the CypA inhibitory mechanism. Consequently, our study has provided a new potential small molecule for curing HCV infection.

  14. 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.

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

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    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...

  16. 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

  17. 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

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

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    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

  19. 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

  20. 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.

  1. 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.

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

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    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

  3. Broad Anti-Hepatitis C Virus (HCV) Antibody Responses Are Associated with Improved Clinical Disease Parameters in Chronic HCV Infection

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    Swann, Rachael E.; Cowton, Vanessa M.; Robinson, Mark W.; Cole, Sarah J.; Barclay, Stephen T.; Mills, Peter R.; Thomson, Emma C.; McLauchlan, John

    2016-01-01

    ABSTRACT During hepatitis C virus (HCV) infection, broadly neutralizing antibody (bNAb) responses targeting E1E2 envelope glycoproteins are generated in many individuals. It is unclear if these antibodies play a protective or a pathogenic role during chronic infection. In this study, we investigated whether bNAb responses in individuals with chronic infection were associated with differences in clinical presentation. Patient-derived purified serum IgG was used to assess the breadth of HCV E1E2 binding and the neutralization activity of HCV pseudoparticles. The binding and neutralization activity results for two panels bearing viral envelope proteins representing either an intergenotype or an intragenotype 1 group were compared. We found that the HCV load was negatively associated with strong cross-genotypic E1E2 binding (P = 0.03). Overall, we observed only a modest correlation between total E1E2 binding and neutralization ability. The breadth of intergenotype neutralization did not correlate with any clinical parameters; however, analysis of individuals with genotype 1 (gt1) HCV infection (n = 20), using an intragenotype pseudoparticle panel, found a strong association between neutralization breadth and reduced liver fibrosis (P = 0.006). A broad bNAb response in our cohort with chronic infection was associated with a single nucleotide polymorphism (SNP) in the HLA-DQB1 gene (P = 0.038), as previously reported in a cohort with acute disease. Furthermore, the bNAbs in these individuals targeted more than one region of E2-neutralizing epitopes, as assessed through cross-competition of patient bNAbs with well-characterized E2 antibodies. We conclude that the bNAb responses in patients with chronic gt1 infection are associated with lower rates of fibrosis and host genetics may play a role in the ability to raise such responses. IMPORTANCE Globally, there are 130 million to 150 million people with chronic HCV infection. Typically, the disease is progressive and is a

  4. 151例血清抗-HCV阳性患者的HCV RNA检测分析%Detection of Serum HCV RNA in Patients with Positive Anti--HCV Reaction

    Institute of Scientific and Technical Information of China (English)

    易冬英; 周福民; 余叔侃

    2001-01-01

    目的:探讨丙型肝炎抗体(抗-HCV)和丙型肝炎病毒核糖核酸(HCV RNA)的关系.方法:研究对间接ELISA法检测抗-HCV阳性患者的血清进行HCV RNA检测(采用RT-PCR法).结果:151例血清抗-HCV阳性患者有85例HCV RNA阳性,阳性率为56.2%.另外,还观察了40例抗HCV阳性病人的双份血清,急性期第一份血清ALT升高、HCV RNA为阳性;经抗病毒治疗后的第二份血清,部分病人ALT复常,HCV RNA阴转,另外部分病人反复ALT异常,HCV RNA则始终为阳性.结论:HCV RNA能鉴别活动性HCV感染及非活动性感染,可为抗病毒药物疗效的评价和临床合理用药提供依据.

  5. Evidence for immune selection of hepatitis C virus (HCV) putative envelope glycoprotein variants: potential role in chronic HCV infections.

    Science.gov (United States)

    Weiner, A J; Geysen, H M; Christopherson, C; Hall, J E; Mason, T J; Saracco, G; Bonino, F; Crawford, K; Marion, C D; Crawford, K A

    1992-01-01

    E2/nonstructural protein 1, the putative envelope glycoprotein (gp72) of HCV, possesses an N-terminal hypervariable (E2 HV) domain from amino acids 384 to 414 of unknown significance. The high degree of amino acid sequence variation in the E2 HV domain appears to be comparable to that observed in the human immunodeficiency virus type 1 gp120 V3 domain. This observation and the observation that the HCV E2 HV domain lacks conserved secondary structure imply that, like the V3 loop of human immunodeficiency virus 1 gp120, the N-terminal E2 region may encode protective epitopes that are subject to immune selection. Antibody-epitope binding studies revealed five isolate-specific linear epitopes located in the E2 HV region. These results suggest that the E2 HV domain is a target for the human immune response and that, in addition to the three major groups of HCV, defined by nucleotide and amino acid sequence identity among HCV isolates, E2 HV-specific subgroups also exist. Analysis of the partial or complete E2 sequences of two individuals indicated that E2 HV variants can either coexist simultaneously in a single individual or that a particular variant may predominate during different episodes of disease. In the latter situation, we found one individual who developed antibodies to a subregion of the E2 HV domain (amino acids 396-407) specific to a variant that was predominant during one major episode of hepatitis but who lacked detectable antibodies to the corresponding region of a second variant that was predominant during a later episode of disease. The data suggest that the variability in the E2 HV domain may result from immune selection. The findings of this report could impact vaccine strategies and drug therapy programs designed to control and eliminate HCV. PMID:1314389

  6. HCV Diversity among Chinese and Burmese IDUs in Dehong, Yunnan, China

    Science.gov (United States)

    Chen, Xin; Duo, Lin; Li, Peilu; Zheng, Yong-Tang; Zhang, Chiyu

    2016-01-01

    HCV transmission is closely associated with drug-trafficking routes in China. Dehong, a prefecture of Yunnan, is the important trade transfer station linking Southeast Asia and China, as well as the drug-trafficking channel linking “Golden triangle” and other regions of China and surrounding countries. In this study, we investigated the HCV genotype diversity among IDUs in Dehong based on 259 HCV positive samples from 118 Chinese and 141 Burmese IDUs. HCV genotypes were determined based on the phylogenies of C/E2 and NS5B genomic sequences. Six HCV subtypes, including 1a, 1b, 3a, 3b, 6n and 6u, were detected. Interestingly, 4 HCV sequences from Burmese IDUs did not cluster with any known HCV subtypes, but formed a well-supported independent clade in the phylogenetic trees of both C/E2 and NS5B, suggesting a potential new HCV subtype circulating in Dehong. Subtype 3b was the predominant subtype, followed by subtypes 6n and 6u. Comparison showed that Dehong had a unique pattern of HCV subtype distribution, obviously different from other regions of China. In particular, HCV subtypes 6u and the potential new HCV subtype had a relatively high prevalence in Dehong, but were rarely detected in other regions of China. There was no significant difference in HCV subtype distribution between Burmese and Chinese IDUs. Few HCV sequences from Burmese and Chinese IDUs clustered together to form transmission clusters. Furthermore, about half of HCV sequences from Burmese IDUs formed small transmission clusters, significantly higher than that from Chinese IDUs (p<0.01). These suggest that the Chinese and Burmese IDUs were relatively isolated from each other in injection drug use behavior and the Burmese IDUs might prefer to inject drugs themselves together. The unique genotype distribution and complex diversity of genotype 6 among IDUs may be associated with the special geographical position of Dehong. PMID:27657722

  7. Significance of CLIA combined with EIA method in detecting anti-HCV and HCV-cAg for HCV primary screening%CLIA法测抗-HCV联合EIA法检测HCV-cAg在HCV感染初筛试验中的意义

    Institute of Scientific and Technical Information of China (English)

    周珍娟; 刘程

    2016-01-01

    目的 探讨自动化学发光免疫分析法(CLIA)测抗-丙型肝炎病毒(抗-HCV)联合酶联免疫法(EIA)测HCV核心抗原(HCV-cAg)在HCV感染初筛试验中的应用价值.方法 采用CLIA法、EIA法检测所有临床标本中抗-HCV和HCV-cAg,比较抗-HCV初筛阳性样本与丙型病毒性肝炎病毒核糖核酸(HCV-RNA)检测结果.结果 本组698例标本中,24例呈阳性,其中23例抗-HCV阳性,9例HCV-cAg阳性,抗-HCV和HCV-cAg检测结果同时阳性者8例.有1例抗-HCV检测阴性,而HCV-cAg检测为阳性,后经HCV-RNA检测证实为HCV感染.24例阳性标本经HCV-RNA检测后,共检出阳性标本17例,其中经HCV-cAg检测为阳性的9例患者均经HCV-RNA检测证实;抗-HCV检测的23例阳性标本中16例经HCV-RNA检测证实为阳性.结论 抗-HCV联合HCV-cAg检测进行HCV感染初筛试验,可降低假阳性率,提高阳性检出率,与HCV-RNA的检测结果符合率高,有利于早期诊断.

  8. 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

  9. 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

  10. 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

  11. Hepatitis C Virus Core Antigen Test in Monitoring of Dialysis Patients

    Directory of Open Access Journals (Sweden)

    Gioacchino Li Cavoli

    2012-01-01

    Full Text Available Hepatitis C virus infection is a persistent worldwide public health concern. The prevalence of HCV infection is much higher in patients on chronic haemodialysis (HD than in the general population. HCV infection can detrimentally affect patients throughout the spectrum of chronic kidney disease. Despite the control of blood products, hepatitis C virus transmission is still being observed among patients undergoing dialysis. Detection systems for serum HCV antibodies are insensitive in the acute phase because of the long serological window. Direct detection of HCV depends on PCR test but this test is not suitable for routine screening. Recent studies have highlighted the importance of HCV core antigen detection as an alternative to PCR. Few studies exist about the efficacy of HCV core antigen test in dialysis population. We studied the utility of HCV core antigen test in routine monitoring of virological status of dialysis patients. We screened 92 patients on long-term dialysis both by PCR HCV-RNA and HCV core antigen test. The sensitivity of HCVcAg test was 90%, the specificity 100%, the positive predictive power 100%, the negative predictive power 97%, and the accuracy 97%. We think serological detection of HCV core antigen may be an alternative to NAT techniques for routine monitoring of patients on chronic dialysis.

  12. Diagnostic accuracy of APRI, FIB-4 and Forns for the detection of liver cirrhosis in HIV/HCV-coinfected patients.

    Science.gov (United States)

    Merli, Marco; Castagna, Antonella; Salpietro, Stefania; Gianotti, Nicola; Messina, Emanuela; Poli, Andrea; Morsica, Giulia; Bagaglio, Sabrina; Cernuschi, Massimo; Bigoloni, Alba; Uberti-Foppa, Caterina; Lazzarin, Adriano; Hasson, Hamid

    2016-04-01

    Non-invasive assessment of liver fibrosis represents an appealing method to monitor liver disease in HCV-infected patients. Currently, transient elastography (TE) is the most accurate non-invasive tool to measure liver stiffness (LS), with the diagnostic accuracy increasing together with the stage of fibrosis (Friedrich Rust et al., 2008; Degos et al., 2010). Stiffness measurement is widely used in the assessment of fibrosis in patients with chronic hepatitis C given its good reproducibility (Fraquelli et al., 2007) and its association with the risk of liver-related complications and death in HIV/HCV-coinfected patients (Fernandez-Montero et al., 2013) and also in patients with compensated HCV-related liver cirrhosis (with or without concomitant HIV-coinfection) (Pérez-Latorre et al., 2014). In the last decade, direct and indirect biomarkers for predicting liver fibrosis have also been developed. Direct fibrosis biomarkers (e.g. FibroTest, FibroMeter) are calculated using serum molecules produced in the presence of liver fibrosis and released in the circulatory system while indirect biomarkers (e.g. APRI, FIB-4, Forns) result from the combination of routine blood tests. Even though indirect biomarkers had a lower diagnostic performance than direct biomarkers and especially TE (Sánchez-Conde et al., 2010; Degos et al., 2010; Castéra et al., 2014), the absence of additional costs and the ready availability make indirect biomarkers a quick and easy non-invasive method to periodically assess liver fibrosis. Since the early detection of liver cirrhosis has a significant impact on both clinical management and treatment decision regarding chronic hepatitis C, we evaluated the threshold and the diagnostic accuracy of APRI, FIB-4 and Forns for the diagnosis of liver cirrhosis in HIV/HCV-coinfected patients.

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

    Directory of Open Access Journals (Sweden)

    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.

  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. 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

  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. Host genetics predict clinical deterioration in HCV-related cirrhosis.

    Directory of Open Access Journals (Sweden)

    Lindsay Y King

    Full Text Available Single nucleotide polymorphisms (SNPs in the epidermal growth factor (EGF, rs4444903, patatin-like phospholipase domain-containing protein 3 (PNPLA3, rs738409 genes, and near the interleukin-28B (IL28B, rs12979860 gene are linked to treatment response, fibrosis, and hepatocellular carcinoma (HCC in chronic hepatitis C. Whether these SNPs independently or in combination predict clinical deterioration in hepatitis C virus (HCV-related cirrhosis is unknown. We genotyped SNPs in EGF, PNPLA3, and IL28B from liver tissue from 169 patients with biopsy-proven HCV cirrhosis. We estimated risk of clinical deterioration, defined as development of ascites, encephalopathy, variceal hemorrhage, HCC, or liver-related death using Cox proportional hazards modeling. During a median follow-up of 6.6 years, 66 of 169 patients experienced clinical deterioration. EGF non-AA, PNPLA3 non-CC, and IL28B non-CC genotypes were each associated with increased risk of clinical deterioration in age, sex, and race-adjusted analysis. Only EGF non-AA genotype was independently associated with increased risk of clinical deterioration (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.31-6.25 after additionally adjusting for bilirubin, albumin, and platelets. Compared to subjects who had 0-1 unfavorable genotypes, the HR for clinical deterioration was 1.79 (95%CI 0.96-3.35 for 2 unfavorable genotypes and 4.03 (95%CI 2.13-7.62 for unfavorable genotypes for all three loci (Ptrend<0.0001. In conclusion, among HCV cirrhotics, EGF non-AA genotype is independently associated with increased risk for clinical deterioration. Specific PNPLA3 and IL28B genotypes also appear to be associated with clinical deterioration. These SNPs have potential to identify patients with HCV-related cirrhosis who require more intensive monitoring for decompensation or future therapies preventing disease progression.

  19. Discovery of an irreversible HCV NS5B polymerase inhibitor.

    Science.gov (United States)

    Zeng, Qingbei; Nair, Anilkumar G; Rosenblum, Stuart B; Huang, Hsueh-Cheng; Lesburg, Charles A; Jiang, Yueheng; Selyutin, Oleg; Chan, Tin-Yau; Bennett, Frank; Chen, Kevin X; Venkatraman, Srikanth; Sannigrahi, Mousumi; Velazquez, Francisco; Duca, Jose S; Gavalas, Stephen; Huang, Yuhua; Pu, Haiyan; Wang, Li; Pinto, Patrick; Vibulbhan, Bancha; Agrawal, Sony; Ferrari, Eric; Jiang, Chuan-kui; Li, Cheng; Hesk, David; Gesell, Jennifer; Sorota, Steve; Shih, Neng-Yang; Njoroge, F George; Kozlowski, Joseph A

    2013-12-15

    The discovery of lead compound 2e was described. Its covalent binding to HCV NS5B polymerase enzyme was investigated by X-ray analysis. The results of distribution, metabolism and pharmacokinetics were reported. Compound 2e was demonstrated to be potent (replicon GT-1b EC50 = 0.003 μM), highly selective, and safe in in vitro and in vivo assays.

  20. 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...

  1. Activity of HDV ribozymes to trans-cleave HCV RNA

    Institute of Scientific and Technical Information of China (English)

    Yue-Cheng Yu; Qing Mao; Chang-Hai Gu; Qi-Fen Li; Yu-Ming Wang

    2002-01-01

    AIM: To explore whether HDV ribozymes have the abilityto trans-cleave HCVRNA.METHODS: Three HDV genomic ribozymes weredesigned and named RzC1, RzC2 and RzC3. Thesubstrate RNA contained HCVRNA 5'-noncoding regionand 5'-fragment of C region (5'-NCR-C). All theribozymes and HCV RNA 5'-NCR-C were obtained bytranscription in vibo from their DNA templates, and HCVRNA 5'-NCR-C was radiolabelled at its 5'-end Undercertain pH, temperature, appropriate concentration ofMg2+ and deionized formamide, these ribozymes wererespectively or simultaneously mixed with HCVRNA 5'-NCR-C and reacted for a certain time. The trans-cleavage reaction was stopped at different time points,and the products were separated with polyacrylamidegel electrophoresis (PAGE), displayed byautoradiography. Percentage of trans-deaved productswas measured to indicate the activity of HDV ribozymes.RESULTS: RzC1 and RzC2 could trans-cleave 26 % and21.8 % of HCV RNA 5'-NCR-C under our reactionconditions with 2.5 mol. L-1 deionized formamiderespectively. The percentage of HCV RNA 5'-NCR-Ctrans-cleaved by RzC1, RzC2 or combined usage of thethree ribozymes increased with time, up to 24.9 %, 20.3 %and 37.3 % respectively at 90 min point. Almost noproduct from RzC3 was observed.CONCLUSION: HDV ribozymes are able to trans-cleavespecifically HCV RNA at certain sites under appropriateconditions, and combination of several ribozymesaiming at different target sites can trans-cleave thesubstrate more efficiently than using only one of them.

  2. 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

  3. Identification of ligands that target the HCV-E2 binding site on CD81.

    Science.gov (United States)

    Olaby, Reem Al; Azzazy, Hassan M; Harris, Rodney; Chromy, Brett; Vielmetter, Jost; Balhorn, Rod

    2013-04-01

    Hepatitis C is a global health problem. While many drug companies have active R&D efforts to develop new drugs for treating Hepatitis C virus (HCV), most target the viral enzymes. The HCV glycoprotein E2 has been shown to play an essential role in hepatocyte invasion by binding to CD81 and other cell surface receptors. This paper describes the use of AutoDock to identify ligand binding sites on the large extracellular loop of the open conformation of CD81 and to perform virtual screening runs to identify sets of small molecule ligands predicted to bind to two of these sites. The best sites selected by AutoLigand were located in regions identified by mutational studies to be the site of E2 binding. Thirty-six ligands predicted by AutoDock to bind to these sites were subsequently tested experimentally to determine if they bound to CD81-LEL. Binding assays conducted using surface Plasmon resonance revealed that 26 out of 36 (72 %) of the ligands bound in vitro to the recombinant CD81-LEL protein. Competition experiments performed using dual polarization interferometry showed that one of the ligands predicted to bind to the large cleft between the C and D helices was also effective in blocking E2 binding to CD81-LEL.

  4. 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

  5. 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.

  6. THE CYTOKINE IP-10 IN CHRONIC HBV AND HCV INFECTION

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    Nina S. Nikolova

    2013-08-01

    Full Text Available Introduction: IP-10 it has been studied as a predictor of treatment response in chronic HCV infected patients. The data for the HBV infection are not enough.Aim: To compare IP-10 levels in patients with chronic HBV /CHB/ and HCV infection /CHC/ and their relation to liver disease and treatment response. Material and methods: 20 patients - with CHC genotype 1 infection /on standard bi-therapy/ and 32 patients with CHB /21 pts - NUC; 11 pts - IFN/. Results: The IP-10 did not correlate with sex, age, ALT and liver fibrosis. The basal IP-10 were lower in patients with CHB (p=0,017. There was a difference in IP-10 baseline levels among the HCV patients with or without RVR (p=0,007. A negative correlation was found between basal IP-10 and RVR (r= -0,508; p=0,008. Conclusion: IP-10 could predict virological response in patients with CHC on standard bi-therapy, but not in HBV infected patients on standard therapy.

  7. Optimum predictors of therapeutic outcome in HCV patients in Pakistan.

    Science.gov (United States)

    Aziz, Hafsa; Raza, Abida; Irfan, Javaid

    2016-01-01

    Hepatitis C virus (HCV) constitutes a major public health issue in Pakistan. Interferon α and ribavirin is used widely in routine practice in HCV infected patients in Pakistan.Treatment prediction is an important tool in therapy management. The present study aims to evaluate trends of predictive variables of treatment outcome in patients with different genotypes. The analysis comprised of 921 patients infected with different HCV genotypes. All the patients received IFN α-2b combined with ribavirin for 24 weeks. Overall, 60.2% patients achieved Sustained virologic response (SVR). In females sustained virologic response (SVR) was higher in age group 84; P = 0.0001), low pretreatment RNA level800,000 IU/ml (4.0; 95%CI, 2.64-6.17; P = 0.0001), early virologic response at week 12 (12.3; 95%CI, 8.18-18.58; P < 0.0001) and non-fatty liver (2.5; 95%CI, 3.6-6.2; P = 0.005) showed significance for SVR. Nucleotide substitution in 5'UTR before treatment failed to show any characteristic pattern that has correlation with sustained response. Subtype 3a showed 95% presence among patients with age <40 years while older patients showed 79.9%.

  8. 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.

  9. Transcriptomic assay of CD8+ T cells in treatment-naive HIV, HCV-mono-infected and HIV/HCV-co-infected Chinese.

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    Jin Zhao

    Full Text Available BACKGROUND: Co-infection with HIV and HCV is very common. It is estimated that over 5 million people are co-infected with HIV and HCV worldwide. Accumulated evidence shows that each virus alters the course of infection of the other one. CD8+ T cells play a crucial role in the eradication of viruses and infected target cells. To the best of our knowledge, no one has investigated the gene expression profiles in HIV/HCV-co-infected individuals. METHODOLOGY: Genome-wide transcriptomes of CD8+ T cells from HIV/HCV-co-infected or mono-infected treatment-naïve individuals were analyzed by microarray assays. Pairwise comparisons were performed and differentially expressed genes were identified followed by quantitative real-time PCR (qRT-PCR validation. Directed Acyclic Graphs (DAG from Web-based Gene SeT AnaLysis Toolkit (WebGestalt and DAVID bioinformatics resources 6.7 (the Database for Annotation, Visualization, and Integrated Discovery were used to discover the Gene Ontology (GO categories with significantly enriched gene numbers. The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG pathways were also obtained by using WebGestalt software. RESULTS AND CONCLUSIONS: A total of 110, 24 and 72 transcript IDs were shown to be differentially expressed (> 2-fold and p<0.05 in comparisons between HCV- and HIV-mono-infected groups, HIV/HCV-co-infected and HIV-mono-infected groups, and HIV/HCV-co-infected and HCV-mono-infected groups, respectively. In qRT-PCR assay, most of the genes showed similar expressing profiles with the observation in microarray assays. Further analysis revealed that genes involved in cell proliferation, differentiation, transcriptional regulation and cytokine responses were significantly altered. These data offer new insights into HIV/HCV co-infections, and may help to identify new markers for the management and treatment of HIV/HCV co-infections.

  10. Proteome Analysis of Liver Cells Expressing a Full- Length Hepatitis C Virus (HCV) Replicon and Biopsy Specimens of Posttransplantation Liver from HCV-Infected Patients

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, Jon M.; Diamond, Deborah L.; Chan, Eric Y.; Gritsenko, Marina A.; Qian, Weijun; Stastna, Miroslava; Baas, Tracey; Camp, David G.; Carithers, Jr., Robert L.; Smith, Richard D.; Katze, Michael G.

    2005-06-01

    The development of a reproducible model system for the study of Hepatitis C virus (HCV) infection has the potential to significantly enhance the study of virus-host interactions and provide future direction for modeling the pathogenesis of HCV. While there are studies describing global gene expression changes associated with HCV infection, changes in the proteome have not been characterized. We report the first large scale proteome analysis of the highly permissive Huh-7.5 cell line containing a full length HCV replicon. We detected > 4,400 proteins in this cell line, including HCV replicon proteins, using multidimensional liquid chromatographic (LC) separations coupled to mass spectrometry (MS). The set of Huh-7.5 proteins confidently identified is, to our knowledge, the most comprehensive yet reported for a human cell line. Consistent with the literature, a comparison of Huh-7.5 cells (+) and (-) the HCV replicon identified expression changes of proteins involved in lipid metabolism. We extended these analyses to liver biopsy material from HCV-infected patients where > 1,500 proteins were detected from 2 {micro}g protein lysate using the Huh-7.5 protein database and the accurate mass and time (AMT) tag strategy. These findings demonstrate the utility of multidimensional proteome analysis of the HCV replicon model system for assisting the determination of proteins/pathways affected by HCV infection. Our ability to extend these analyses to the highly complex proteome of small liver biopsies with limiting protein yields offers the unique opportunity to begin evaluating the clinical significance of protein expression changes associated with HCV infection.

  11. 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.

  12. 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.

  13. Cell penetrable humanized-VH/V(H)H that inhibit RNA dependent RNA polymerase (NS5B) of HCV.

    Science.gov (United States)

    Thueng-in, Kanyarat; Thanongsaksrikul, Jeeraphong; Srimanote, Potjanee; Bangphoomi, Kunan; Poungpair, Ornnuthchar; Maneewatch, Santi; Choowongkomon, Kiattawee; Chaicumpa, Wanpen

    2012-01-01

    NS5B is pivotal RNA dependent RNA polymerase (RdRp) of HCV and NS5B function interfering halts the virus infective cycle. This work aimed to produce cell penetrable humanized single domain antibodies (SdAb; VH/V(H)H) that interfere with the RdRp activity. Recombinant NS5BΔ55 of genotype 3a HCV with de novo RNA synthetic activity was produced and used in phage biopanning for selecting phage clones that displayed NS5BΔ55 bound VH/V(H)H from a humanized-camel VH/V(H)H display library. VH/V(H)H from E. coli transfected with four selected phage clones inhibited RdRp activity when tested by ELISA inhibition using 3'di-cytidylate 25 nucleotide directed in vitro RNA synthesis. Deduced amino acid sequences of two clones showed V(H)H hallmark and were designated V(H)H6 and V(H)H24; other clones were conventional VH, designated VH9 and VH13. All VH/V(H)H were linked molecularly to a cell penetrating peptide, penetratin. The cell penetrable VH9, VH13, V(H)H6 and V(H)H24 added to culture of Huh7 cells transfected with JHF-1 RNA of genotype 2a HCV reduced the amounts of RNA intracellularly and in culture medium implying that they inhibited the virus replication. VH/V(H)H mimotopes matched with residues scattered on the polymerase fingers, palm and thumb which were likely juxtaposed to form conformational epitopes. Molecular docking revealed that the antibodies covered the RdRp catalytic groove. The transbodies await further studies for in vivo role in inhibiting HCV replication.

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

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    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.

  15. 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

    . Using CD81-deficient Huh7 cells, we further demonstrated the importance of A970T/I1312V/A2919T or A970T/C2419R/A2919T for virus assembly and that the I1312V/C2419R combination played a major role in virus release. Using a similar approach, we found that NS5B mutation F2994R, identified here from culture...... efficient infectious cell culture systems for these genotype 1a strains by using the HCV-1/SF9_A and H77C in vivo infectious clones. We initially adapted a genome with the HCV-1 5'UTR-NS5A (where UTR stands for untranslated region) and the JFH1 NS5B-3'UTR (5-5A recombinant), including the genotype 2a......-adapted full-length TN viruses and a common NS3 helicase mutation (S1368P) derived from viable H77C and HCV-1 5-5A recombinants, initiated replication and culture adaptation of H77C containing LSG and TNcc(1a)-adaptive mutations. An H77C recombinant harboring 19 mutations (H77Ccc) replicated and spread...

  16. 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

  17. 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...

  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. Patient Characteristics and Prescribing Patterns Associated with Sofosbuvir Treatment for Chronic HCV Infection in a Commercially Insured Population

    Science.gov (United States)

    Tambourine, Brent M.; Sadeghi, Arash; Yang, Jianing; Stockl, Karen M.; Lew, Heidi C.; Solow, Brian K.; Tran, Josephine N.

    2016-01-01

    fibrosis was not known or could not be determined. Of the members with documented liver fibrosis, 49.6% were determined by liver biopsy. Conclusion The results show that the initial prescribing of sofosbuvir often included the off-label interferon-free regimen of sofosbuvir plus simeprevir during the study period (of note, this combination regimen was approved by the FDA in November 2014, after the completion of the study period). The off-label prescribing pattern may be attributable to “warehousing” of patients who were awaiting more tolerable therapies. Furthermore, the limited utilization of noninvasive tests to assess liver fibrosis suggests that providers may benefit from additional education on these methods. Although this analysis provides insight into the treatment of patients with chronic HCV immediately after the launch of sofosbuvir in the United States, future research should reevaluate the treatment patterns of chronic HCV infection to capture recent advances in the treatment of this disease. PMID:27182426

  20. Hepatic compartmentalization of exhausted and regulatory cells in HIV/HCV-coinfected patients.

    Science.gov (United States)

    Barrett, L; Trehanpati, N; Poonia, S; Daigh, L; Sarin, S Kumar; Masur, H; Kottilil, S

    2015-03-01

    Accelerated intrahepatic hepatitis C virus (HCV) pathogenesis is likely the result of dysregulation within both the innate and adaptive immune compartments, but the exact contribution of peripheral blood and liver lymphocyte subsets remains unclear. Prolonged activation and expansion of immunoregulatory cells have been thought to play a role. We determined immune cell subset frequency in contemporaneous liver and peripheral blood samples from chronic HCV-infected and HIV/HCV-coinfected individuals. Peripheral blood mononuclear cells (PBMC) and biopsy-derived liver-infiltrating lymphocytes from 26 HIV/HCV-coinfected, 10 chronic HCV-infected and 10 HIV-infected individuals were assessed for various subsets of T and B lymphocytes, dendritic cell, natural killer (NK) cell and NK T-cell frequency by flow cytometry. CD8(+) T cells expressing the exhaustion marker PD-1 were increased in HCV-infected individuals compared with uninfected individuals (P = 0.02), and HIV coinfection enhanced this effect (P = 0.005). In the liver, regulatory CD4(+) CD25(+) Foxp3(+) T cells, as well as CD4(+) CD25(+) PD1(+) T cells, were more frequent in HIV/HCV-coinfected than in HCV-monoinfected samples (P HIV infection (P ≤ 0.005 for all). Low CD8(+) expression was observed only in PD-1(+) CD8(+) T cells from HCV-infected individuals and healthy controls (P = 0.002) and was associated with enhanced expansion of exhausted CD8(+) T cells when exposed in vitro to PHA or CMV peptides. In conclusion, in HIV/HCV coinfection, ongoing HCV replication is associated with increased regulatory and exhausted T cells in the periphery and liver that may impact control of HCV. Simultaneous characterization of liver and peripheral blood highlights the disproportionate intrahepatic compartmentalization of immunoregulatory T cells, which may contribute to establishment of chronicity and hepatic fibrogenesis in HIV coinfection.

  1. 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.

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

    Science.gov (United States)

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

    2012-01-01

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

  3. 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

  4. 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

  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. 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.

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

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    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.

  8. 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

  9. Safety of cyclosporin A in HCV-infected patients: experience with cyclosporin A in patients affected by rheumatological disorders and concomitant HCV infection.

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    Galeazzi, Mauro; Bellisai, Francesca; Giannitti, Chiara; Manganelli, Stefania; Morozzi, Gabriella; Sebastiani, Gian Domenico

    2007-09-01

    Because of the relatively high prevalence of both hepatitis C virus (HCV) infection and autoimmune disorders (ADs), it is not rare to encounter in daily clinical practice patients with ADs also carrying HCV. Corticosteroids and/or immunosuppressant drugs are needed to treat ADs, but they place HCV-infected patients at risk of worsening the infection. So, rheumatologists have often refrained from using corticosteroids or immunosuppressants in AD when HCV-RNA is also present. Cyclosporin A (CsA) is an immunosuppressive agent used to treat a wide range of ADs, but there is a large evidences in the literature, both in vitro and in vivo, suggesting that CsA also exerts an inhibitory effect on HCV replication at standard therapeutic dose. Therefore, this evidence has opened new ways to improve the therapy and the prognosis in patients with HCV-related liver diseases, including those with transplants. Recent reports, although limited in number, also suggest the safety of CsA in the treatment of patients with AD and concomitant HCV infection. In this review we also report our personal experience on the combination treatment with CsA and anti-TNF-alpha agents in rheumatoid arthritis.

  10. HCV derived from sera of HCV-infected patients induces pro-fibrotic effects in human primary fibroblasts by activating GLI2

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    Granato, M.; Zompetta, C.; Vescarelli, E.; Rizzello, C.; Cardi, A.; Valia, S.; Antonelli, G.; Marchese, C.; Torrisi, M. R.; Faggioni, A.; Cirone, M.

    2016-01-01

    Hepatitis C virus (HCV) infection is a leading cause of liver fibrosis, especially in developing countries. The process is characterized by the excess accumulation of ECM that may lead, over time, to hepatic cirrhosis, liver failure and also to hepatocarcinoma. The direct role of HCV in promoting fibroblasts trans-differentiation into myofibroblasts, the major fibrogenic cells, has not been fully clarified. In this study, we found that HCV derived from HCV-infected patients infected and directly induced the trans-differentiation of human primary fibroblasts into myofibroblasts, promoting fibrogenesis. This effect correlated with the activation of GLI2, one of the targets of Hedgehog signaling pathway previously reported to be involved in myofibroblast generation. Moreover, GLI2 activation by HCV correlated with a reduction of autophagy in fibroblasts, that may further promoted fibrosis. GLI2 inhibition by Gant 61 counteracted the pro-fibrotic effects and autophagy inhibition mediated by HCV, suggesting that targeting HH/GLI2 pathway might represent a promising strategy to reduce the HCV-induced fibrosis. PMID:27476557

  11. 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

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

    2016-01-01

    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

  12. 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

  13. Dynamic of Mixed HCV Infection in Plasma and PBMC of HIV/HCV Patients Under Treatment With Peg-IFN/Ribavirin.

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    Bagaglio, Sabrina; Uberti-Foppa, Caterina; Di Serio, Clelia; Trentini, Filippo; Andolina, Andrea; Hasson, Hamid; Messina, Emanuela; Merli, Marco; Porrino, Lucy; Lazzarin, Adriano; Morsica, Giulia

    2015-10-01

    The extent of mixed hepatitis C virus (HCV) genotype in different compartments (plasma and peripheral blood mononuclear cell, PBMC) and possible association with treatment efficacy in HIV/HCV coinfected patients remains to be unknown.The objective of this study was to elucidate the frequency of mixed genotype infection (MG), its profile in different compartments during anti-HCV treatment, and the possible influence of different genotypes on the response rate.The compartmentalization of HCV population was investigated by next-generation sequencing in 19 HIV/HCV coinfected patients under anti-HCV treatment with peginterferon/ribavirin (P-R). Ten individuals were nonresponder (NR) or relapser (RE) to P-R treatment and 9 had a sustained virological response (SVR).Eleven/nineteen (58%) patients had MG in plasma compartment. Ten or 12 patients infected by a difficult to treat genotype (DTG) 1 or 4 as dominant strain, had an MG, whereas only 1/7 individuals infected by easy to treat genotype (ETG) harbored a mixed genotype, P = 0.006. HCV-RNA was more frequently detected in PBMC of NR (10/10) than in those of SVR (5/9), P = 0.032. Mixed genotype infection was detected in 6/15 (40%) PBMC-positive cases and was not associated with P-R treatment response. By multivariate analysis, MG in plasma samples was the most important viral factor affecting the treatment response (P = 0.0237).Detection of MG in plasma of HIV/HCV coinfected patients seems to represent the major determinant of response to P-R treatment. This finding may have important clinical implication in light of the new therapeutic approach in HIV/HCV coinfected individuals suggesting that combination treatment with direct acting antivirals could be less effective in MG.

  14. 抗-HCV、HCV-RNA、ALT在HCV感染病程中的分布%THEDEVELOPMENT OF ANTI-HCV、HCV-RAN AND ALT LEVEL IN HCV CLINICAL PATIENTS AND ITS EPIDEMIOLOGICAL SIGNIFICANCE

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    王晓俭; 任志胜; 吴敏

    2003-01-01

    目的:了解抗-HCV、HCV-RNA、ALT在输血后HCV感染者病程中的动态变化.方法:运用ELISA法及PCR法对205例输血后肝炎进行检测,对105例输血后HCV感染病例进行追踪调查.结果:抗-HCV及HCV-RNA阳性率分别为57.1%和55.1%,抗-HCV阴性中HCV-RNA阳性率达30.2%.抗-HCV、HCV-RNA及ALT在急性及慢性病人临床病程中呈现不同的特点.结论:PCR法在HCV感染的确诊、血源筛选等方面具有一定的流行病学意义.

  15. 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.

  16. Distribution of HCV genotype and single nucleotide polymorphisms (SNPs of IL-28B gene in HIV/HCV-coinfected Thai populations

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    A Avihingsanon

    2012-11-01

    Full Text Available Introduction: Hepatitis C virus (HCV infection remains a major silent killer, worldwide, particularly in resource poor settings where treatment of hepatitis C is mainly impossible. Pegylated interferon-α (PEG-IFN plus ribavirin (RBV are the recommended treatment for patients with chronic hepatitis C genotype 2/3. Recent study revealed that treatment responses against HCV infection by PEG-IFN and RBV are significantly associated with the single nucleotide polymorphisms (SNPs of interleukin-28B (IL-28B gene. There is limited data about the HCV genotype and SNPs of IL-28B in HIV-infected Thai population. Therefore, we aimed to investigate HCV genotype and the SNP patterns of the IL-28B gene in our HIV/HCV coinfection. Methods: Quantification of HCV RNA was done by a real-time polymerase chain reaction assay (Abbott with lower limit of detection of <12 copies/ml. HCV RNA-positive samples based on reverse transcriptase-polymerase chain reaction (RT-PCR of the 5'UTR were amplified with primer specific for the core and NS5B regions. Nucleotide sequences of both regions were analyzed for the genotype by phylogenetic analysis. DNA sample was extracted from PBMCs or sera. Then SNPs within IL-28B gene were detected by TaqMan real-time PCR (rs8099917 and rs12979860. The data were analyzed by allelic discrimination (AD software on the ABI-7900HT. Results: Totally 60 HIV/HCV-coinfected patients were studied. Median HCV RNA were 5.8 log10 copies/mL, 70% of them had HCV RNA >100,000 copies/mL. After sequencing, the phylogenetic analyses in this study showed that genotype 3 was the most prevalent in this population (56%; following by genotype 1 (30% and 6 (13%. Approximately 4% of them had infected for both genotypes 1 and 3. For IL-28B at rs8099917 and rs12979860 position, 95% of them were major allele (T/T or C/C and 5% were heterozygous (T/G or C/T. Conclusions: HCV genotype 3 is the most prevalent in our HIV/HCV coinfection. 95% of our patients have

  17. Níveis de vale de ciclosporina elevados em transplantados renais anti-HCV positivos Elevated cyclosporine A trough levels in HCV positive kidney transplant recipients

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    Luciano Wolffenbüttel

    2003-06-01

    Full Text Available OBJETIVO: Comparar os níveis de vale de CsA de transplantados renais anti-HCV+ com um grupo controle. MÉTODOS: Incluímos como casos todos os pacientes anti-HCV+ transplantados entre janeiro de 1992 e abril de 1996, e os anti-HCV- transplantados a seguir do caso como controles. Excluímos pacientes diabéticos, HbsAg+, os que recebiam fármacos com interação com a CsA e aqueles com transaminases elevadas. A sorologia para HCV foi testada pelo método ELISA de 3ª geração, e as dosagens de ciclosporina através de fluorimetria polarizada com anticorpo policlonal. RESULTADOS: As principais variáveis demográficas não diferiram entre os grupos. O nível de vale médio de CsA do primeiro mês pós-transplante foi maior nos 23 pacientes anti-HCV+ (551 ± 280 ng/ml do que nos 31 controles (418 ± 228 ng/ml, pOBJECTIVE: Compare the CsA trough levels of HCV+ kidney transplant recipients to a control group METHODS: All anti-HCV positive patients that received a renal allograft between January 1992 and April 1996 were initially included as cases. Patients with diabetes mellitus, HBsAg+, who were taking medication that could modify CsA pharmacokinetics and those with elevated aminotransferases were excluded. For each anti-HCV positive index case the following transplanted anti-HCV negative patient was included as a control. Third generation ELISA was used for determination of the anti-HCV status and CsA dosages were performed by polarized fluorometry with polyclonal antibodies. RESULTS: No differences in the demographic variables were found. The average CsA through levels in the first month were higher (551 ± 280 ng/ml in the 23 cases as compared to the 31 controls (418 ± 228 ng/ml; p< 0.05. The differences became apparent at the end of the first week (528 ± 275 versus 344 ± 283 ng/ml; p<0.01 and persisted at discharge (582 ± 284 versus 457 ± 229; p=0,08. CONCLUSION: We concluded that anti-HCV positive patients have higher blood levels of Cs

  18. Correlation between HIV and HCV in Brazilian prisoners: evidence for parenteral transmission inside prison Correlação entre HIV e HCV em prisioneiros brasileiros: evidência de transmissão parenteral no encarceramento

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    MN Burattini

    2000-10-01

    Full Text Available OBJECTIVE: It is an accepted fact that confinement conditions increase the risk of some infections related to sexual and/or injecting drugs practices. Mathematical techniques were applied to estimate time-dependent incidence densities of HIV infection among inmates. METHODS: A total of 631 prisoners from a Brazilian prison with 4,900 inmates at that time were interviewed and their blood drawn. Risky behavior for HIV infection was analyzed, and serological tests for HIV, hepatitis C and syphilis were performed, intended as surrogates for parenteral and sexual HIV transmission, respectively. Mathematical techniques were used to estimate the incidence density ratio, as related to the time of imprisonment. RESULTS: Prevalence were: HIV -- 16%; HCV -- 34%; and syphilis -- 18%. The main risk behaviors related to HIV infection were HCV prevalence (OR=10.49 and the acknowledged use of injecting drugs (OR=3.36. Incidence density ratio derivation showed that the risk of acquiring HIV infection increases with the time of imprisonment, peaking around three years after incarceration. CONCLUSIONS: The correlation between HIV and HCV seroprevalence and the results of the mathematical analysis suggest that HIV transmission in this population is predominantly due to parenteral exposure by injecting drug, and that it increases with time of imprisonment.OBJETIVO: É um fato correntemente aceito que as condições de confinamento aumentam o risco de algumas infecções relacionadas às práticas sexuais e/ou ao uso de drogas injetáveis. Realizou-se estudo para estimar a densidade de incidência da infecção pelo HIV na população prisional com aplicação de técnicas matemáticas. MÉTODOS: Foram entrevistados em São Paulo, SP, 631 prisioneiros da maior prisão da América do Sul, que abrigava aproximadamente 4.900 presos na ocasião do estudo. Foi colhido sangue da população entrevistada, analisado o risco para a infecção pelo HIV e realizados testes

  19. 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

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

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    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

  1. The usefulness of Umelosa hepatitis C vírus qualitative kit as supplemental test for confirmation of hepatitis C virus infection Utilidade do teste Umelosa vírus da hepatite C qualitativo como teste suplementar para confirmação da infecção pelo vírus da hepatite C

    Directory of Open Access Journals (Sweden)

    Idania Gonzalez-Perez

    2004-02-01

    Full Text Available Forty voluntary blood donors from two different blood banks in Havana, Cuba, who were repeatedly reactive on the routine screening of antibodies to hepatitis C virus, by Umelisa HCV test, were analyzed for the presence of HCV RNA using a nested PCR assay of the HCV 5' untranslated region, Umelosa HCV qualitative. Sera from 45 patients of a specialized gastroenterology consultation, positive to Umelisa HCV, were also assayed with the Umelosa HCV qualitative, to establish their condition related to the presence of HCV RNA previously to the indication of a treatment or after three, six or twelve months of antiviral therapy. Serum HCV-RNA was detected in 21/40 (52.5% donors who had repeatedly positive ELISA results, confirming the HCV infection for them. In specialized consultation HCV-RNA was detected by PCR analysis in 30/45 (66% analyzed sera.Quarenta doadores de sangue voluntários de dois bancos de sangue em Havana, Cuba, repetidamente reativos ao exame de rotina para anticorpos contra o vírus da hepatite C, pelo teste Umelisa HCV, foram analisados para a presença de RNA HCV através de um ensaio de PCR da região 5' não-traduzida do HCV denominado Umelosa HCV qualitativo. Amostras de soro obtidas de 45 pacientes atendidos em consulta gastroenterológica especializada, positivos para Umelisa HCV, também foram avaliados através do Umelosa HCV qualitativo, para estabelecer sua condição em relação à presença de RNA HCV previamente à indicação de um tratamento ou após três, seis ou doze meses de terapia anti-viral. O RNA HCV sérico foi detectado em 21/40 (52,5% doadores que haviam apresentado resultados ELISA positivos repetidos, confirmando a infecção por HCV. Nos pacientes atendidos em consulta especializada, o RNA HCV foi detectado por análise de PCR em 30/45 (66% amostras de soro analisadas.

  2. Design and development of an in-house multiplex RT-PCR assay for simultaneous detection of HIV-1 and HCV in plasma samples

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    M Paryan

    2012-03-01

    Full Text Available Background and Objectives: HIV-1 and HCV infections are life threatening problems in patients who receive blood products. Serological methods have proven useful in detecting these infections, but there are setbacks that make it challenging to detect these infectious agents. By the advent of Nucleic Acid Testing (NAT methods, especially in multiplex format, more precise detection is possible.Materials and Methods: We have developed a multiplex RT-PCR assay for simultaneous detection of HIV-1 and HCV. Primers were designed for highly conserved region of genome of each virus. Using these primers and standard plasmids, we determined the limit of detection, clinical and analytical specificity and sensitivity of the assay. Monoplex and multiplex RT-PCR were performed.Results: Analytical sensitivity was considered to be 100 and 200 copies/ml for HIV-1 and HCV, respectively. High concentration of one virus had no significant effect on the detection of the other one with low concentration. By analysis of 40 samples, clinical sensitivity of the assay was determined to be 97.5%. Using different viral and human genome samples, the specificity of the assay was evaluated to be 100%.Conclusions: The aim of this study was to develop a reliable, rapid and cost effective method to detect HIV-1 and HCV simultaneously. Results showed that this simple and rapid method is perfectly capable of detecting two viruses in clinical samples.

  3. 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

  4. 抗-HCV-IgG阳性血清检测HCV的临床意义%The clinical values for the definifive detection of HCV in sever clinical cases such as positive HCV-IgG

    Institute of Scientific and Technical Information of China (English)

    张建华; 钟怀印; 薛承岩

    2007-01-01

    了解抗-HCV-IgG阳性时、仅肝功能轻度异常、与HCV感染者有接触史时等临床情况下HCV在血液内存的几率,验证在这些临床情况时开展检测HCV确证试验的临床意义.采集血清为检测标本,用ELISA技术检测抗-HCV-IgG,RT-PCR技术检测HCV-RNA.血清HCV-RNA的检出率,抗-HCV-IgG阳性组为41.9%、仅肝功能轻度异常组为25.7%、无症状体检组为29.4%.临床对抗-HCV-IgG阳性者、仅肝功能轻度异常者、有接触史者等特殊人群应做检测HCV的确证试验,RT-PCR技术可以用做临床检测HCV的确证试验方法.

  5. 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.

  6. 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

  7. 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...

  8. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 河北省HIV-1感染者中HCV和HBV合并感染状况调查%Study on HCV and HBV co-infection among HIV-1 infected people in Hebei Province

    Institute of Scientific and Technical Information of China (English)

    赵翠英; 李巧敏; 赵宏儒; 路新利; 白广义; 李岩; 王莹莹; 王伟

    2012-01-01

    Objective To study the ratios of HCV and HBV co-infection among HIV-1 infected people in Hebei Province. Method Peripheral blood was collected for testing HCV antibody and HBsAg in HIV-1 infected individuals. Results Of the 147 HIV-1 infected individuals receiving blood tests, 17. 7% (26/147) were infected with HCV, 15. 0% (22/147) were infected with HBV,and 3. 4%(5/147) were co-infected with HCV/HBV. The statistical a-nalysis showed a significant difference in the ratios of HCV co-infection among individuals who were infected with HIV through different routes(P<0. 001). The ratios of HCV co-infection were 100. 0%(6/6)in injecting drug users. In those infected via blood transmission and sexual behaviors,the ratios of HCV co-infection were 73. 3%(11/ 15) and 6. 3%(7/lll)respectively. HIV infected females had a higher ratio of HCV co-infection than males (P = 0. 002). Statistically significant difference was found in ratio of HCV co-infection among individuals with various educational backgrounds (P<0. 01). HIV infected individuals with lower education had higher HCV co-infection rati-o. Statistically significant difference was also observed in ratio of HCV co-infection among HIV infected individuals of different ages (P<0. 05). HIV infected individuals of lowe_r age had higher HBV co-infection ratio.' Conclusion There are higher ratios of HCV and HBV co-infection in HIV-1 infected individuals.%目的 了解河北省艾滋病病毒Ⅰ型(HIV-1)感染者中,丙型肝炎病毒(HCV)、乙型肝炎(乙肝)病毒(HBV)的感染状况.方法 采集了HIV-1感染者的抗凝全血样品,进行了HCV抗体和乙肝病毒表面抗原(HBsAg)的检测.结果 147例HIV-1感染者中,HCV感染率为17.7%(26/147),HBV感染率为15.0%(22/147),HCV/HBV混合感染率为3.4%(5/147).在HIV-1感染者中,HCV的感染率在注射吸毒感染者中为100%(6/6),血液途径感染者中为73.3%(11/15),性感染者中为6.3%(7/111),不同感染途径间

  11. 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

  12. Brief Report: European Mitochondrial Haplogroups Impact on Liver Fibrosis Progression Among HCV and HIV/HCV-Coinfected Patients From Northwest Spain.

    Science.gov (United States)

    Tabernilla, Andres; Rego-Pérez, Ignacio; Grandal, Marta; Pernas, Berta; Pértega, Sonia; Delgado, Manuel; Mariño, Ana; Álvarez, Hortensia; Mena, Alvaro; Rodríguez-Osorio, Iria; Pedreira, Jose Domingo; Blanco, Francisco Javier; Poveda, Eva

    2016-10-01

    The impact of mitochondrial DNA haplogroups on the outcome of liver fibrosis was evaluated in 362 hepatitis C virus infection (HCV)-monoinfected and HIV/HCV-coinfected patients (147 and 215, respectively) in clinical follow-up at 2 reference hospitals in the Northwest of Spain. The mitochondrial DNA haplogroup H was the most prevalent (50.3%) in this population. The cluster Others and V were recognized as risk factors for the development of liver fibrosis while haplogroup H and HCV genotype 4 confer a lower risk. This information might be useful for prioritization of HCV treatment, especially for F0-F1 patients for whom there is no urgency for treatment.

  13. Discovery of SCH446211 (SCH6): A New Ketoamide Inhibitor of the HCV NS3 Serine Protease and HCV Subgenomic RNA Replication

    Energy Technology Data Exchange (ETDEWEB)

    Bogen, Stephane L.; Arasappan, Ashok; Bennett, Frank; Chen, Kevin; Jao, Edwin; Liu, Yi-Tsung; Lovey, Raymond G.; Venkatraman, Srikanth; Pan, Weidong; Parekh, Tajel; Pike, Russel E.; Ruan, Sumei; Liu, Rong; Baroudy, Bahige; Agrawal, Sony; Chase, Robert; Ingravallo, Paul; Pichardo, John; Prongay, Andrew; Brisson, Jean-Marc; Hsieh, Tony Y.; Cheng, Kuo-Chi; Kemp, Scott J.; Levy, Odile E.; Lim-Wilby, Marguerita; Tamura, Susan Y.; Saksena, Anil K.; Girijavallabhan, Viyyoor; Njoroge, F. George (SPRI)

    2008-06-30

    Introduction of various modified prolines at P{sub 2} and optimization of the P{sub 1} side chain led to the discovery of SCH6 (24, Table 2), a potent ketoamide inhibitor of the HCV NS3 serine protease. In addition to excellent enzyme potency (K*{sub i} = 3.8 nM), 24 was also found to be a potent inhibitor of HCV subgenomic RNA replication with IC{sub 50} and IC{sub 90} of 40 and 100 nM, respectively. Recently, antiviral activity of 24 was demonstrated with inhibition of the full-length genotype 2a HCV genome. In addition, 24 was found to restore the responsiveness of the interferon regulatory factor 3 (IRF-3) in cells containing HCV RNA replicons.

  14. 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...

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

    Directory of Open Access Journals (Sweden)

    Valli De Re

    2014-01-01

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

  16. Function of monocytes in chronic HCV infection: Role for IL-10 and interferon

    NARCIS (Netherlands)

    B. Liu (Bi Sheng)

    2011-01-01

    textabstractHepatitis C virus (HCV) establishes persistent infection in about 80% of the infected individuals. The symptoms are initially mild in those persistently infected patients, and it may take decades before the serious consequences of chronic HCV infection become apparent. Up to 20% of infec

  17. Antiviral Therapy for Chronic HCV Infection: Virological Response and Long-Term Outcome

    NARCIS (Netherlands)

    A.J.P. van der Meer (Adriaan)

    2014-01-01

    markdownabstract__Abstract__ Hepatitis C is a major global health problem which is responsible for over 350,000 deaths each year.1 In total, there are thought to be around 150 million hepatitis C virus (HCV) carriers, which comprise about 3% of the world population. The prevalence of HCV infection,

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Molecular signatures associated with HCV-induced hepatocellular carcinoma and liver metastasis.

    Directory of Open Access Journals (Sweden)

    Valeria De Giorgi

    Full Text Available Hepatocellular carcinomas (HCCs are a heterogeneous group of tumors that differ in risk factors and genetic alterations. In Italy, particularly Southern Italy, chronic hepatitis C virus (HCV infection represents the main cause of HCC. Using high-density oligoarrays, we identified consistent differences in gene-expression between HCC and normal liver tissue. Expression patterns in HCC were also readily distinguishable from those associated with liver metastases. To characterize molecular events relevant to hepatocarcinogenesis and identify biomarkers for early HCC detection, gene expression profiling of 71 liver biopsies from HCV-related primary HCC and corresponding HCV-positive non-HCC hepatic tissue, as well as gastrointestinal liver metastases paired with the apparently normal peri-tumoral liver tissue, were compared to 6 liver biopsies from healthy individuals. Characteristic gene signatures were identified when normal tissue was compared with HCV-related primary HCC, corresponding HCV-positive non-HCC as well as gastrointestinal liver metastases. Pathway analysis classified the cellular and biological functions of the genes differentially expressed as related to regulation of gene expression and post-translational modification in HCV-related primary HCC; cellular Growth and Proliferation, and Cell-To-Cell Signaling and Interaction in HCV-related non HCC samples; Cellular Growth and Proliferation and Cell Cycle in metastasis. Also characteristic gene signatures were identified of HCV-HCC progression for early HCC diagnosis.A diagnostic molecular signature complementing conventional pathologic assessment was identified.

  20. HIV合并HCV感染者抗HCV疗效分析%HIV co-infectde with HCV efficacy of anti-HCV

    Institute of Scientific and Technical Information of China (English)

    蒙艳; 胡海燕; 霍松; 陈梅; 周玲; 李佳; 韩本发

    2014-01-01

    By HIV co-infected with HCV to regulate anti-HCV therapy, understand the highly active antiretroviral therapy (HAART) on the basis of the efficacy of anti-HCV therapy. The national anti-HIV laboratory diagnosis of HIV infection confirmed HCV-RNA positive patients, while 30 were randomly divided into A, B groups, A group during the HAART treatment while giving recombinant human interferon α-2b and ribavirin injection ribavirin capsules for anti-HCV treatment, B group were given HAART treatment, analysis of relevant indicators before and after treatment. A , B group of stable HAART therapy, A group of anti-HCV in patients with early viral response (EVR) rate of 60% sustained virologic response (SVR) rate was 37.5%. In the HAART treatment on the basis of anti-HCV treatment does not affect the efficacy of HAART; HIV combined HCV infection for anti-HCV treatment efficacy can be; without the SVR patients, anti-HCV treatment can improve the patient's clinical symptoms.%目的:通过对HIV合并HCV感染者进行规范抗HCV治疗,了解在高效抗逆转录病毒治疗(HAART)基础上进行抗HCV治疗的疗效。方法经国家抗HIV确认实验室确诊为HIV感染同时HCV-RNA阳性患者30名,随机分为A、B两组,A组在进行HAART治疗的同时给予重组人干扰素α-2b注射液及利巴韦林胶囊进行抗HCV治疗,B组单纯给予HAART治疗,对治疗前后相关指标进行分析。结果 A、B组HAART治疗疗效稳定,A组患者抗HCV早期病毒应答(EVR)率为60%,持续病毒学应答(SVR)率为33%。结论在HAART治疗基础上进行抗HCV治疗并不影响HAART疗效;HIV合并HCV感染者进行抗HCV治疗的疗效可;在未获得SVR的患者中,抗HCV治疗能使患者的临床症状改善。

  1. 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...

  2. Patterns of Healthcare Utilization Among Veterans Infected With Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) and Coinfected With HIV/HCV: Unique Burdens of Disease

    Science.gov (United States)

    Katrak, Shereen; Park, Lawrence P.; Woods, Christopher; Muir, Andrew; Hicks, Charles; Naggie, Susanna

    2016-01-01

    Background. Hepatitis C virus (HCV) infection is a leading cause of cirrhosis and the primary cause of liver transplantation in the United States, and coinfection with human immunodeficiency virus (HIV) increases the risk of comorbidities. However, healthcare utilization (HCU) patterns among HIV/HCV-coinfected patients are poorly understood. This study compared the rates of HCU and reasons for hospital admission among HCV-infected, HIV-infected, and HIV/HCV-coinfected veterans. Methods. Hepatitis C virus- and HIV-infected and HIV/HCV-coinfected veterans in care with the Department of Veterans Affairs (VA) from 1998 to 2009 (n = 335 371, n = 28 179, n = 13 471, respectively) were identified by HIV- and HCV-associated International Classification of Diseases, Ninth Revision codes from the clinical case registry. We assessed rates of HCU using emergency department (ED) visits, outpatient visits, and hospitalization and primary diagnoses associated with hospitalization. Independent risk factors associated with hospitalization were also examined. Results. Rates of outpatient and ED visits increased over the 11-year study period for all groups, with inpatient admission rates remaining stable. The HCU rates were consistently higher for the coinfected than other cohorts. The primary reason for hospital admission for all groups was psychiatric disease/substance use, accounting for 44% of all admissions. Nadir CD4 500 cells/mm3. Conclusions. As the current population of HCV-infected, HIV-infected, and HIV/HCV-coinfected veterans age, they will continue to place a substantial and increasing demand on the US healthcare system, particularly in their utilization of ED and outpatient services. These data suggest the need for an ongoing investment in mental health and primary care within the VA healthcare system. PMID:27704025

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

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    Kali Zhou

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

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

    Science.gov (United States)

    Wang, Charles; Hu, Fengyu; Ning, Chuanyi; Lan, Yun; Tang, Xiaoping; Tucker, Joseph D.; Cai, Weiping

    2016-01-01

    Background The advent of direct-acting agents (DAAs) has improved treatment of HCV in HIV co-infection, but may be limited by primary drug resistance. This study reports the prevalence of natural polymorphisms conferring resistance to NS3/4A protease inhibitors and NS5B polymerase inhibitors in treatment-naïve HIV/HCV co-infected individuals in China. Methods Population based NS3/4A sequencing was completed for 778 treatment-naïve HIV/HCV co-infected patients from twelve provinces. NS3 sequences were amplified by nested PCR using in-house primers for genotypes 1–6. NS5B sequencing was completed for genotyping in 350 sequences. Resistance-associated variants (RAVs) were identified in positions associated with HCV resistance. Results Overall, 72.8% (566/778) of all HCV sequences had at least one RAV associated with HCV NS3/4A protease inhibitor resistance. Variants were found in 3.6% (7/193) of genotype 1, 100% (23/23) of genotype 2, 100% (237/237) of genotype 3 and 92% (299/325) of genotype 6 sequences. The Q80K variant was present in 98.4% of genotype 6a sequences. High-level RAVs were rare, occurring in only 0.8% of patients. 93% (64/69) patients with genotype 1b also carried the C316N variant associated with NS5B low-level resistance. Conclusions The low frequency of high-level RAVs associated with primary HCV DAA resistance among all genotypes in HIV/HCV co-infected patients is encouraging. Further phenotypic studies and clinical research are needed. PMID:27341031

  5. Clinical Application Evaluation of Some Kinds of Method in the Detection of HCV Antibody%几种丙肝抗体检测的临床应用评价

    Institute of Scientific and Technical Information of China (English)

    廖冰洁; 周迎春; 谢在春; 梁淑慧

    2012-01-01

    目的 探讨两种不同孵育时间的酶联免疫吸附试验(ELISA)与化学发光微粒子免疫分析(CMIA)三种方法检测血清中丙肝抗体(抗-HCV)的临床运用.方法 分别用两种ELISA和CMIA测定门诊和住院患者抗-HCV样本1 281例.不一致的用PCR法进行丙型肝炎病毒核酸(HCV-RNA)定量检测.结果 1 281例样本ELISA A 18例阳性,阳性率为1.41%;ELISA B 20例阳性,阳性率为1.56%;CMIA 31例阳性,阳性率为2.42%.两种ELISA分别与CMIA阳性率比较x2分别为8.47,6.67;P值分别为0.003 6,0.009 8(P<0.05),差异均有统计学意义;两种ELISA法阳性率比较x2为0.50,P=0.479 5(P>0.05),差异无统计学意义.两种ELISA与CMIA结果不一致的标本用PCR测HCV-RNA,结果除1例CMIA为阳性HCV-RNA-PCR为阴性外,其余CMIA与HCV-RNA-PCR定量结果一致.结论 CMIA优于ELISA灵敏、特异度高、结果准确,CMIA更适合于丙型肝炎的临床筛查应用;ELISA B比ELISA A灵敏.%Objective To discuss the clinical application with two kinds different incubation time of ELISA and CMIA in the detection of patient HCV antibody. Methods The serum anti-HCV of 1 281 cases of in patients was detected using two kinds of ELISA and CMIA. With PCR method for quantitative detection of HCV nucleic acid(HCV-RNA) to inconsistent results. Results The HCV antibody positive sample detected by ELISA A were 18, with the positive rate of 1.41%) by ELISA B were 20,with the positive rate of 1. 56%; while by CMIA were 31, with the positive rate of 2.42%. ELISA and CMIA were significant differences ( P0. 05) ^ was 0. 50 and P was equal to 0. 479 5. The inconsistent results tested by HCV-RNA.CMIA and HCV-RNA Results were consistent. Expect for 1 cases of CMIA positive and HCV-RNA-PCR negative. Conclusion Compared with ELISA,CMIA might be sensitive,high specificity and with accurate results. Therefore CMIA could be applied to screen HCV infection. ELISA B might be more sensitive than ELISA A.

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

    Science.gov (United States)

    Adinolfi, Luigi Elio; Rinaldi, Luca; Guerrera, Barbara; Restivo, Luciano; Marrone, Aldo; Giordano, Mauro; Zampino, Rosa

    2016-01-01

    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. PMID:27231906

  7. 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.

  8. Cyclosporine as Monotherapy for Psoriasis in the Setting of Chronic HCV Infection: A Forgotten Therapeutical Option

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    Alexandra Maria Giovanna Brunasso

    2012-05-01

    Full Text Available Background: Treatment of psoriasis in the setting of chronic hepatitis C virus (HCV infection is diffcult, because standard therapies like methotrexate are associated with increased hepatic toxicity. Due to the HCV suppressive effect. Cyclosporine may represent a valid systemic alternative for psoriatic-HCV patients.Objectives: In this study, we report the successful usage of intermittent cycles of cyclosporine in the setting of chronic HCV infection and we try to call the attention once again in a very effective and forgotten therapeutic option for severe chronic plaque psoriasis.Observation: We describe a 48 years - old patient who has a 20 year history of severe chronic plaque psoriasis and HCV infection (aminotransferase levels are three times normal; HCV genotype 2a-2c and HCV-RNA titer of 2.050.000 UI-ml. Five courses (range of duration of three to six months of oral cyclosporine (5 mg/kg/day were followed during a 38 month period. The viral load and the transaminases’ levels diminished during the 38 months of intermittent cyclosporine therapy to the lowest level measured at 36th month. The good psoriatic response was associated to a slight improvement of the liver condition, even though the HCV-RNA was reduced by less than 1 log10 without normalization of aminotransferase’ levels.Conclusions: The reduced liver toxicity, the potential anti-HCV properties and the well-known systemic anti-inflammatory effect, make cyclosporine a good alternative for recalcitrant psoriatic patients with HCV-liver disease.

  9. Reduced IFNλ4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes

    DEFF Research Database (Denmark)

    Terczynska-Dyla, Ewa; Bibert, Stephanie; Duong, Francois H T;

    2014-01-01

    Hepatitis C virus (HCV) infections are the major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma worldwide. Both spontaneous and treatment-induced clearance of HCV depend on genetic variation within the interferon-lambda locus, but until now no clear causal relationship has...... of poor HCV clearance....

  10. Non-A, non-B hepatitis and the anti-HCV assay.

    Science.gov (United States)

    Barbara, J A; Contreras, M

    1991-01-01

    The successful cloning of a non-structural antigen from the genome of what is now designated as the 'hepatitis C virus' (HCV) has transformed an erstwhile diagnosis of exclusion for non-A, non-B hepatitis (NANBH). The assay has been validated against panels of known infectivity for NANBH and sera from haemophiliac patients treated either with virally inactivated or uninactivated factor VIII. The predictive value of the assay is being assessed clinically in prospective studies of post-transfusion hepatitis and by using laboratory techniques such as polymerase chain reaction. While the assay shows good predictability in high-risk subjects, an appreciable number of false-positive results are likely in blood donor populations. Furthermore, the extent of infectivity of seropositive blood donors is still the subject of active research. The prevalence of anti-HCV in blood donors varies from approximately 0.2 to 1.5% around the world, based on repeat reactivity in the Ortho antiglobulin ELISA assay. These rates may be appreciably reduced following supplementary testing with recombinant immunoblot assay (RIBA). Prevalence data in African sera are as yet unreliable, pending assessment by RIBA, presumably because of high levels of IgG interfering with the assay. Presence of anti-HBc or elevated alanine aminotransferase associates to a greater or lesser extent with seropositivity, especially when both surrogate markers are present, but conversely many (unconfirmed) seropositive subjects lack these surrogate markers. An understanding of the modes of transmission of HVC is of obvious importance to transfusion practice. Intravenous drug use is a striking risk factor, but the contribution made by sexual transmission is not so clear.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1711260

  11. 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...

  12. 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

  13. 5-Benzothiazole substituted pyrimidine derivatives as HCV replication (replicase) inhibitors.

    Science.gov (United States)

    Arasappan, Ashok; Bennett, Frank; Girijavallabhan, Vinay; Huang, Yuhua; Huelgas, Regina; Alvarez, Carmen; Chen, Lei; Gavalas, Stephen; Kim, Seong-Heon; Kosinski, Aneta; Pinto, Patrick; Rizvi, Razia; Rossman, Randall; Shankar, Bandarpalle; Tong, Ling; Velazquez, Francisco; Venkatraman, Srikanth; Verma, Vishal A; Kozlowski, Joseph; Shih, Neng-Yang; Piwinski, John J; MacCoss, Malcolm; Kwong, Cecil D; Clark, Jeremy L; Fowler, Anita T; Geng, Feng; Kezar, Hollis S; Roychowdhury, Abhijit; Reynolds, Robert C; Maddry, Joseph A; Ananthan, Subramaniam; Secrist, John A; Li, Cheng; Chase, Robert; Curry, Stephanie; Huang, Hsueh-Cheng; Tong, Xiao; Njoroge, F George

    2012-05-01

    Based on a previously identified HCV replication (replicase) inhibitor 1, SAR efforts were conducted around the pyrimidine core to improve the potency and pharmacokinetic profile of the inhibitors. A benzothiazole moiety was found to be the optimal substituent at the pyrimidine 5-position. Due to potential reactivity concern, the 4-chloro residue was replaced by a methyl group with some loss in potency and enhanced rat in vivo profile. Extensive investigations at the C-2 position resulted in identification of compound 16 that demonstrated very good replicon potency, selectivity and rodent plasma/target organ concentration. Inhibitor 16 also demonstrated good plasma levels and oral bioavailability in dogs, while monkey exposure was rather low. Chemistry optimization towards a practical route to install the benzothiazole moiety resulted in an efficient direct C-H arylation protocol.

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

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    Solange Zacalusni Freitas

    2014-12-01

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

  15. 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.

  16. 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

  17. Anti-HCV immunoassays based on a multiepitope antigen and fluorescent lanthanide chelate reporters.

    Science.gov (United States)

    Salminen, Teppo; Juntunen, Etvi; Khanna, Navin; Pettersson, Kim; Talha, Sheikh M

    2016-02-01

    There is a need for simple to produce immunoassays for hepatitis C virus (HCV) antibody capable of detecting all genotypes worldwide. Current commonly used third generation immunoassays use three to six separate recombinant proteins or synthetic peptides. We have developed and expressed in Escherichia coli a single recombinant antigen incorporating epitopes from different HCV proteins. This multiepitope protein (MEP) was used to develop two types of HCV antibody immunoassays: a traditional antibody immunoassay using a labeled secondary antibody (indirect assay) and a double-antigen assay with the same MEP used as capture binder and labeled binder. The secondary antibody assay was evaluated with 171 serum/plasma samples and double-antigen assay with 148 samples. These samples included an in-house patient sample panel, two panels of samples with different HCV genotypes and a seroconversion panel. The secondary antibody immunoassay showed 95.6% sensitivity and 100% specificity while the double-antigen assay showed 91.4% sensitivity and 100% specificity. Both assays detected samples from all six HCV genotypes. The results showed that combining a low-cost recombinant MEP binder antigen with a high sensitivity fluorescent lanthanide reporter can provide a sensitive and specific immunoassay for HCV serology. The results also showed that the sensitivity of HCV double-antigen assays may suffer from the low avidity immune response of acute infections.

  18. 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.

  19. 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.

  20. Discovery of cellular proteins required for the early steps of HCV infection using integrative genomics.

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    Ji Hoon Park

    Full Text Available Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early steps of hepatitis C virus (HCV infection. By integrating HCV and human protein associations, co-expression data, and tight junction-tetraspanin web specific networks, we identified host proteins required for the early steps in HCV infection. Moreover, we validated the roles of newly identified proteins in HCV infection by knocking down their expression using small interfering RNAs. Specifically, a novel host factor CD63 was shown to directly interact with HCV E2 protein. We further demonstrated that an antibody against CD63 blocked HCV infection, indicating that CD63 may serve as a new therapeutic target for HCV-related diseases. The candidate gene list provides a source for identification of new therapeutic targets.

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

    Science.gov (United States)

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

    2014-01-01

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

  2. Logical Analysis of Regulation of Interleukin-12 Expression Pathway Regulation During HCV Infection.

    Science.gov (United States)

    Farooqi, Zia-Ur-Rehman; Tareen, Samar H K; Ahmed, Jamil; Zaidi, Najam-Us-Sahar S

    2016-01-01

    Hepatitis C virus (HCV) triggers coordinated innate and adaptive response in host cell. HCV genome and proteins of the replicating virus are recognized as non-self-antigens by host cell to activate Toll Like Receptors (TLRs). Activated TLRs ultimately express cytokines, which can clear virus either by activating interferon (IFN), protein kinase C (PKC) and RNA Lase system or through activation of cytotoxic T-lymphocytes. Interleukin-12 (IL-12) is a potent antiviral cytokine, capable of clearing HCV by bridging both innate and adaptive antiviral immune response. Activation of TLR-4 on macrophages surface induces expression of IL-12 via NF-κB and AP-1 transcriptional pathway. After expression, IL- 12 releases IFN-γ, which activates anti-HCV cytotoxic lymphocytes. Conversely, in chronic HCV infection downregulation of IL-12 has been reported instead of by number of studies. Keeping in view of the above mentioned facts, this study was designed to evaluate HCV-core mediated down-regulation of IL-12 transcriptional pathway by employing a logical modeling approach based on the Ren´e Thomas formalism. The logical parameters of entities were estimated by using SMBioNet. The Logical model represents all possible dynamics of protein expression involved during course of HCV pathology. Results demonstrated that at chronic stage of infection, though TLR-4 was constantly active but yet it failed to express the NF-κB, AP-1, IL-12 and IFN-γ. This mechanism was indicative of incorporation of core mediated changes in IL-12 regulatory pathway. Moreover, results also indicate that HCV adopts different trajectories to accomplish the persistence of chronic phase of infection. It also implicated that human immune system tries to clear HCV but core is capable of inducing system oscillations to evade the immunity.

  3. 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.

  4. 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.

  5. 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.

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

    Science.gov (United States)

    Adinolfi, Luigi Elio; Rinaldi, Luca; Guerrera, Barbara; Restivo, Luciano; Marrone, Aldo; Giordano, Mauro; Zampino, Rosa

    2016-01-01

    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. PMID:27231906

  7. 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.

  8. Different Responses of Two Highly Permissive Cell Lines Upon HCV Infection

    Institute of Scientific and Technical Information of China (English)

    Honghe Chen; Rongjuan Pei; Xinwen Chen

    2013-01-01

    The construction of the first infectious clone JFH-1 speeds up the research on hepatitis C virus (HCV).However,Huh7 cell line was the only highly permissive cell line for HCV infection and only a few clones were fully permissive.In this study,two different fully permissive clones of Huh7 cells,Huh7.5.1 and Huh7-Lunet-CD81 (Lunet-CD81) cells were compared for their responses upon HCV infection.The virus replication level was found slightly higher in Huh7.5.1 cells than that in Lunet-CD81 cells.Viability of Huh7.5.1 cells but not of Lunet-CD81 cells was reduced significantly after HCV infection.Further analysis showed that the cell cycle of infected Huh7.5.1 cells was arrested at G1 phase.The G1/S transition was blocked by HCV infection in Huh7.5.1 cells as shown by the cell cycle synchronization analysis.Genes related to cell cycle regulation was modified by HCV infection and gene interaction analysis in GeneSpring GX in Direct Interactions mode highlighted 31 genes.In conclusion,the responses of those two cell lines were different upon HCV infection.HCV infection blocked G1/S transition and cell cycle progress,thus reduced the cell viability in Huh7.5.1 cells but not in Lunet-CD81 cells.Lunet-CD81 cells might be suitable for long term infection studies of HCV.

  9. 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.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Chelyapov Nickolas

    2006-09-01

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

  12. 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

  13. Successful treatment with sofosbuvir of fibrosing cholestatic hepatitis C after liver transplantation in an HIV-HCV-coinfected patient.

    Science.gov (United States)

    Borentain, Patrick; Colson, Philippe; Dhiver, Catherine; Gregoire, Emilie; Hardwigsen, Jean; Botta-Fridlund, Danielle; Garcia, Stéphane; Gerolami, René

    2015-01-01

    Fibrosing cholestatic hepatitis is a severe form of post-liver transplantation HCV recurrence. Fibrosing cholestatic hepatitis is characterized by its early onset and severe prognosis in HIV-infected patients. We report the case of an HIV-HCV genotype-4 coinfected patient successfully treated with a combination of sofosbuvir and ribavirin. After 4 weeks of treatment we observed a resolution of HCV recurrence related symptoms associated with a normalization of liver biochemistry and dramatic decrease of HCV viral load. This case illustrates the efficiency and tolerance of a sofosbuvir-based anti-HCV interferon-free regimen in post-liver HCV recurrence. Because of the absence of drug interactions between sofosbuvir and antiretroviral treatment or calcineurin inhibitors, its administration in HIV-HCV-coinfected liver transplanted patients is very promising.

  14. Interpreting serologic tests for hepatitis C virus infection: balancing cost and clarity.

    Science.gov (United States)

    Long, G S; Bacon, B R; Bisceglie, A M

    1996-09-01

    Although progress has been made toward developing a cheap and accurate method to diagnose hepatitis C virus (HCV) infection, current screening tests have an unacceptably high false-positive rate. Newer tests are more accurate, but also more costly. This paper outlines an approach for interpreting and using these different tests. The second-generation enzyme-linked immunosorbent assay (ELISA) for HCV antibodies, the current screening test for HCV infection, has a sensitivity of approximately 90% but a low specificity. Persons with risk factors for HCV infection, elevated aminotransferase levels, and a positive ELISA result most likely have HCV infection. Confirmatory testing with a recombinant immunoblot assay adds considerably to the cost of diagnosis and should only be used to confirm HCV infection in ELISA-positive patients at low risk or with conditions such as hyperglobulinemia that promote false-positive reactivity. Polymerase chain reaction (PCR) testing is the most sensitive and accurate method of diagnosing HCV infection, but its cost limits its use. PCR testing should be reserved for cases of diagnostic uncertainty, evaluation of possible acute hepatitis C, patients with normal serum aminotransferase levels and anti-HCV antibodies, and patients about to undergo interferon therapy. PMID:8870336

  15. 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...

  16. Computer-aided identification, synthesis and evaluation of substituted thienopyrimidines as novel inhibitors of HCV replication.

    Science.gov (United States)

    Bassetto, Marcella; Leyssen, Pieter; Neyts, Johan; Yerukhimovich, Mark M; Frick, David N; Brancale, Andrea

    2016-11-10

    A structure-based virtual screening technique was applied to the study of the HCV NS3 helicase, with the aim to find novel inhibitors of the HCV replication. A library of ∼450000 commercially available compounds was analysed in silico and 21 structures were selected for biological evaluation in the HCV replicon assay. One hit characterized by a substituted thieno-pyrimidine scaffold was found to inhibit the viral replication with an EC50 value in the sub-micromolar range and a good selectivity index. Different series of novel thieno-pyrimidine derivatives were designed and synthesised; several new structures showed antiviral activity in the low or sub-micromolar range.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    Isabelle Poizot-Martin

    Full Text Available 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.Cross-sectional study of all HIV/HCV coinfected patients attending at least one visit in 2012 in the multicenter French Dat'AIDS cohort. A simulation of drug-drug interactions between antiretroviral treatment and DAAs available in 2015 was performed.Of 16,634 HIV-infected patients, 2,511 had detectable anti-HCV antibodies, of whom 1,196 had a detectable HCV-RNA and were not receiving HCV treatment at the time of analysis. 97.1% of these patients were receiving cART and 81.2% had a plasma HIV RNA <50 copies/mL. cART included combinations of nucleoside reverse transcriptase inhibitors with a boosted protease inhibitor in 43.6%, a non-nucleoside reverse transcriptase inhibitor in 17.3%, an integrase inhibitor in 15.4% and various combinations or antiretroviral drugs in 23.7% of patients. A previous treatment against HCV had been administered in 64.4% of patients. Contraindicated associations/potential interactions were expected between cART and respectively sofosbuvir (0.2%/0%, sofosbuvir/ledipasvir (0.2%/67.6%, daclatasvir (0%/49.4%, ombitasvir/boosted paritaprevir (with or without dasabuvir (34.4%/52.2% and simeprevir (78.8%/0%.Significant potential drug-drug interactions are expected between cART and the currently available DAAs in the majority of HIV/HCV coinfected patients. Sofosbuvir/ledipasvir and sofosbuvir/daclatasvir with or without ribavirin appeared the most suitable combinations in our population. A close collaboration between hepatologists and HIV/AIDS specialists appears necessary for the management of HCV treatment concomitantly to cART.

  19. Early quantification of HCV core antigen may help to determine the duration of therapy for chronic genotype 2 or 3 HCV infection

    DEFF Research Database (Denmark)

    Alsiö, A; Jannesson, A; Langeland, N;

    2012-01-01

    The aim of the present study was to evaluate the utility of hepatitis C virus (HCV) core antigen (coreAg) assessment for the identification of candidates for short-term therapy. Plasma samples from HCV genotype 2 or 3-infected patients participating in the NORDynamIC trial (n = 382) comparing 12...... and 24 weeks of combination treatment with pegylated interferon-α2a and a fixed dose of 800 mg ribavirin daily were analyzed for coreAg. Among the 126 patients (33% of the intention-to-treat population) achieving HCV coreAg levels in plasma below 0.2 pg/mL when assayed on treatment day 3, sustained viral...... were 89% and 95%, respectively. Twelve weeks of combination treatment may be sufficient for genotype 2 or 3-infected patients achieving HCV coreAg levels below 0.2 pg/mL by day 3, signaling a rapid clearance of HCV viremia....

  20. 大理地区HCV感染及合并HIV感染患者血细胞和生化指标变化的研究%Studies on Changes of Indexes of Blood Cells and Biochemistry in Patients with Co-infection of HCV and HIV in Dali Area

    Institute of Scientific and Technical Information of China (English)

    王佳丽

    2015-01-01

    Objective :To analyze the difference in blood cells and blood biochemical criterion between the patients in‐fected with HCV and patients co‐infected with HCV and HIV ,to provide the basis for the diagnosis and treatment of the patients with HCV and the patients combined with HIV infection .Methods :We performed the detection on the blood cells and blood biochemical criterion of the patients with HCV ,HCV combined with HIV ,and besides the two formers from our hospital in January to September 2013 ,and the test results were analyzed by variance approach of SPSS17 .0 .Results :Compared with the group on the patients non‐infected with HCV and HIV ,the level of RBC ,HGB , PLT ,HCT ,K + and Ca2 + were obviously decreased(P< 0 .05) ,but the level of ALT ,AST ,AKP ,GGT and TBA were obviously increased(P< 0 .05)in the group on patients with HCV .Infection on HCV patients combined with HIV ag‐gravate the decrease of level of RBC ,HGB ,PLT and HCT (P< 0 .05) ,further more decrease of level of WBC and in‐crease of level of TBA was more markedly(P< 0 .01) .Conclusion :The analysis results were suggested that the progres‐sion of HCV patients was aggravated by co‐infected with HIV ,and there were great significance in diagnose ,cure and prognosis along with variety of blood cells and blood biochemical criterion of hepatitis C patients and hepatitis C pa‐tients co‐infected with HIV .%目的:了解大理地区 HCV 感染及其合并 HIV 感染患者血细胞和生化结果变化,为单纯性 HCV 感染及其合并HIV 感染患者的诊断和治疗提供依据。方法:收集2013年1-9月我院单纯性 HCV 感染患者、合并 HIV 感染患者、排除 HCV 和 HIV 感染患者的血细胞和生化指标,并采用 SPSS17.0软件进行统计学分析。结果:HCV 感染后会使患者 RBC 、HGB 、PLT 、HCT 、K +和 Ca2+水平明显降低(P<0.05),ALT 、AST 、AKP 、GGT 和 TBA 水平明显升高(P<0.05);而合并 HIV

  1. Seroprevalence and risk factors for hepatitis C virus (HCV) infection in pregnant women attending public sector tertiary care hospital in Hyderabad Sindh

    OpenAIRE

    Bibi, Seema; Dars, Saira; Ashfaq, Sanober; Ara Qazi, Roshan; Akhund, Sadaf

    2013-01-01

    Background and Objectives: Pakistan is among the countries having high prevalence of HCV infection in the population but there is dearth of proper epidemiological data regarding acquisition of HCV infection in the pregnant population. Our objective was to determine the seroprevalence of HCV antibodies in healthy pregnant women and to assess the potential risk factors for HCV infection in HCV positive subjects and in the control group. Methodology: This cross sectional and comparative study wa...

  2. High interferon-stimulated gene ISG-15 expression affects HCV treatment outcome in patients co-infected with HIV and HCV.

    Science.gov (United States)

    Katsounas, Antonios; Hubbard, Jonathan J; Wang, Crystal H; Zhang, Xiaozhen; Dou, Diana; Shivakumar, Bhavana; Winter, Sophie; Schlaak, Joerg F; Lempicki, Richard A; Masur, Henry; Polis, Michael; Kottilil, Shyam; Osinusi, Anu

    2013-06-01

    Increased baseline expression and lack of induction of interferon-stimulated genes (ISG) are strong negative predictors of therapeutic response to PegIFN/RBV in patients co-infected with HIV and hepatitis C virus (HCV). This study specifically addressed whether ISG-15 expression influences therapeutic responses in 20 HIV/HCV genotype-1 subjects undergoing HCV treatment. Non-responders had significantly higher baseline expression and selective induction of ISG-15 after IFN-α treatment relative to participants with sustained virological response. High baseline levels of ISG-15 were also associated with less induction of ISG with treatment. These results support a role for ISG-15 as a prognostic indicator and resistance factor to IFN-α.

  3. Antiviral phytochemicals identification from Azadirachta indica leaves against HCV NS3 protease: an in silico approach.

    Science.gov (United States)

    Ashfaq, Usman Ali; Jalil, Asma; Ul Qamar, Muhammad Tahir

    2016-08-01

    Hepatitis C virus (HCV) is a major health problem across the world affecting the people of all age groups. It is the main cause of hepatitis and at chronic stage causes liver cirrhosis and hepatocellular carcinoma. Various therapeutics are made against HCV but still there is a need to find out potential therapeutics to combat the virus. The goal of this study is to identify the phytochemicals of Azadirachta indica leaves having antiviral activity against HCV NS3 protease through molecular docking and simulation approach. Results show that the compound 3-Deacetyl-3-cinnamoyl-azadirachtin possesses good binding properties with HCV NS3/4A protease. It can be concluded from this study that Deacetyl-3-cinnamoyl-azadirachtin may serve as a potential inhibitor against NS3/4A protease. PMID:26274064

  4. Synthesis and biological evaluation of sophocarpinic acid derivatives as anti-HCV agents

    Directory of Open Access Journals (Sweden)

    Yinghong Li

    2014-08-01

    Full Text Available Chronic hepatitis C virus (HCV infection has become a major public health burden worldwide. Twenty-two sophocarpinic acid or matrine derivatives were synthesized and their anti-HCV activities were evaluated in vitro. The structure-activity analysis revealed that (i sophocarpinic acids with a D-seco 3-ring structure scaffold were more favorable than matrines with a 4-ring scaffold; (ii the introduction of an electron-withdrawing group on the phenyl ring in 12-N-benzenesulfonyl Δβγ sophocarpinic acids was beneficial for the antiviral activity against HCV. Among them, compounds 9h and 9j exhibited the most potent inhibitory activities on HCV replication with selectivity indies of 70.3 and 30.9, respectively. Therefore, both were selected as antiviral candidates for further investigation.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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...... number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries...... studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep...

  8. Results Analysis of 283 Cases of HIV/HCV Complicated with Infection%283例HIV/HCV合并感染检测结果分析

    Institute of Scientific and Technical Information of China (English)

    杨高峰; 周永玲; 王智龙

    2014-01-01

    Objective Understanding of HIV/HCV co-infection in zhumadian area.Methods Using enzyme-linked immunosorbent assay (ELISA) double antigen testing clamp method.Results HIV/HCV co-infection in 2000~2005 year infection in 213 cases (75%), other years (25%). Sel blood infection in 198 cases (69%), 51 cases (18%), sexual transmission of blood transfusion infection in 26 cases (9.1%), and from mother to child vertical infection in 8 cases (2.8%).Conclusion Zhumadian City HIV/HCV co-infection in recent years is on the decline, but infected with HCV alone showed a trend of rise, this has led to the local government at aches great importance to, is take the necessary testing and prevention measures.%目的了解驻马店地区HIV/HCV合并感染状况。方法采用酶联免疫吸附试验(ELISA)双抗原夹心法进行检测。结果HIV/HCV合并感染年份2000年~2005年感染213例(75%),其他年份(25%)。卖血感染198例(69%),性传播51例(18%),输血感染26例(9.1%),母婴垂直感染8例(2.8%)。结论驻马店市HIV/HCV合并感染最近几年呈下降趋势,但HCV单独感染呈升趋势,这已经引起当地政府高度重视,正采取必要检测和防治措施。

  9. 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

  10. Genetic Variability of Hepatitis C Virus (HCV 5' Untranslated Region in HIV/HCV Coinfected Patients Treated with Pegylated Interferon and Ribavirin.

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    Iwona Bukowska-Ośko

    Full Text Available Association between hepatitis C virus (HCV quasispecies and treatment outcome among patients with chronic hepatitis C has been the subject of many studies. However, these studies focused mainly on viral variable regions (E1 and E2 and usually did not include human immunodeficiency virus (HIV-positive patients. The aim of the present study was to analyze heterogeneity of the 5' untranslated region (5'UTR in HCV/HIV coinfected patients treated with interferon and ribavirin. The HCV 5'UTR was amplified from serum and peripheral blood mononuclear cells (PBMC samples in 37 HCV/HIV coinfected patients treated for chronic hepatitis C. Samples were collected right before treatment, and at 2, 4, 6, 8, 12, 20, 24, 36, 44, 48, 60, and 72 weeks. Heterogeneity of the 5'UTR was analyzed by single strand conformational polymorphism (SSCP, cloning and sequencing. Sustained virological response (SVR was achieved in 46% of analyzed HCV/HIV co-infected patients. Stable SSCP band pattern was observed in 22 patients (62.9% and SVR rate among these patients was 23%. Decline in the number of bands and/or shift in band positions were found in 6 patients (17.1%, 5 (83% of whom achieved SVR (p=0.009. A novel viral genotype was identified in all but one of these patients. In 5 of these 6 patients a new genotype was dominant. 5'UTR heterogeneity may correlate with interferon and ribavirin treatment outcome. In the analyzed group of HCV/HIV coinfected patients, viral quasispecies stability during treatment favored viral persistence, whereas decrease in the number of variants and/or emergence of new variants was associated with SVR. Among injection drug users (IDU patients, a new genotype may become dominant during treatment, probably due to the presence of mixed infections with various strains, which have different susceptibility to treatment.

  11. Antibody screening tests variably overestimate the prevalence of hepatitis C virus infection among HIV-infected adults in Ghana.

    Science.gov (United States)

    King, S; Adjei-Asante, K; Appiah, L; Adinku, D; Beloukas, A; Atkins, M; Sarfo, S F; Chadwick, D; Phillips, R O; Geretti, A M

    2015-05-01

    HIV coinfection with HCV has been poorly studied in sub-Saharan Africa, and the reliability of available seroprevalence estimates remains uncertain. The study aim was to determine HCV RNA prevalence in HIV-infected subjects receiving care in Kumasi, Ghana, and relate the findings to HCV antibody detection. From a population of 1520 HIV-infected adults, all HBsAg-positive subjects (n = 236) and a random subset of HBsAg-negative subject (n = 172) were screened for HCV RNA using pooled plasma; positive samples were genotyped by core and NS5B sequencing. HCV antibodies were detected by three commercial screening assays and confirmed by the line immunoassay. HCV RNA was detected in 4/408 subjects (1.0%, 95% confidence interval 0.0-1.9%), comprising 3/236 (1.3%; 0.0-2.8%) HBsAg-positive and 1/172 (0.6%; 0.0-1.8%) HBsAg-negative subjects. HCV RNA-positive subjects showed reactivity in all three antibody screening assays. Among HCV RNA-negative subjects, 5/67 (7.5%), 5/67 (7.5%) and 19/67 (28.4%) showed antibody reactivity by each screening assay, respectively, including two (3.0%) with reactivity by all three assays. Only one sample (1.5%) had confirmed antibody reactivity by line immunoassay indicating past HCV infection. HCV-positive subjects (three males, two females) were aged 30-46 years, by questionnaire-based interview reported surgical procedures and blood transfusion as risk factors for infection. HCV genotypes were 2 (subtypes 2j, 2l, 2k/unassigned) and 1 (subtype unassigned). Without further testing, HCV antibody screening assays variably overestimated HCV prevalence among HIV-infected subjects in Ghana. These findings inform the interpretation of previous seroprevalence estimates based upon screening assays alone.

  12. 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...

  13. Venue-Based Networks May Underpin HCV Transmissions amongst HIV-Infected Gay and Bisexual Men

    Science.gov (United States)

    Bradshaw, Daniel; Raghwani, Jayna; Jacka, Brendan; Sacks-Davis, Rachel; Lamoury, Francois; Down, Ian; Prestage, Garrett; Applegate, Tanya L.; Hellard, Margaret; Sasadeusz, Joe; Dore, Gregory J.; Pybus, Oliver G.; Matthews, Gail V.; Danta, Mark

    2016-01-01

    Background This study aimed to investigate the potential influence of venue-based networks on HCV transmission in HIV-positive gay and bisexual men (GBM). Methods This was a prospectively recruited cohort of HIV-infected GBM with recently-acquired HCV infection resident in Melbourne and Sydney. Clinical and demographic data were collected together with blood samples for HCV sequencing. Phylogenies were inferred and clusters of individuals infected with HCV with genetic sequence homology were identified. Venues used for sourcing sexual partners were identified; sourcing partners from the same venue was considered a potential social link. Using the Jaccard similarity coefficient, associations were identified between the network of sites where men sourced sex partners and transmission relationships as defined by phylogenetic clustering. Results Forty individuals were recruited, of whom 62.5% were considered to have sexually- and 37.5% IDU-acquired HCV. Venue use was consistent with men being members of a more sexually adventurous gay community subculture. Six phylogenetically-determined pairs or clusters were identified, comprising fifteen (15/28, 53.6%) individuals. Participants belonging to phylogenetic clusters were observed within the same networks. There was a significant correlation between the network and phylogenetic clustering when both cities were considered simultaneously (p = 0.005), raising the possibility that social connections may be important for HCV transmissions. Conclusions Venue-based network elicitation is a promising approach for elucidating HCV transmissions amongst HIV-infected GBM. Public health approaches targeting individuals and venues prominent within networks may reduce onward HCV transmission. PMID:27584149

  14. 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.

  15. Analysis on CD4 + CD25 + T cell in HCV infection and HCV/HIV co-infection%HCV感染者和HCV/HIV合并感染者免疫调节

    Institute of Scientific and Technical Information of China (English)

    康辉; 尚红; 刁莹莹; 范霞; 代娣; 姜桐军; 耿文清

    2005-01-01

    目的探讨我国单纯丙型肝炎病毒(HCV)感染者和HCV/HIV合并感染者免疫应答的相关机制.方法分离人外周血单个核细胞;流式细胞仪(FACS)检测CD4+T细胞和CD4+CD25+T细胞表达水平.结果CD4+CD25+T细胞占外周血单个核细胞中CD4+T细胞比例(%CD4+CD25+),HCV感染组明显高于健康对照组(19.2%>13.8%,P<0.05),HCV/HIV合并感染组明显低于对照组(6.9%<13.8%,P<0.001),更明显低于HCV感染组(P<0.001).结论HCV感染者体内CD4+CD25+T细胞增殖明显,提示CD4+CD25+T细胞在HCV慢性感染中发挥免疫调节作用.HCV/HIV合并感染时,CD4+CD25+T细胞受损,从而影响免疫调节功能.

  16. Detection and analysis of HCV RNA and anti-HCV in patients with hepatitis C%丙型肝炎患者HCV RNA与抗-HCV检测结果分析

    Institute of Scientific and Technical Information of China (English)

    宋秀军; 李伟; 陈舒; 于慧杰; 江其生

    2010-01-01

    @@ 丙型肝炎是由丙型肝炎病毒(HCV)引起的病毒性传染病.HCV由于基因组的结构和表型特征而归属于黄病毒家簇单股正链RNA病毒,其病毒核酸(HCV RNA)的检测是诊断HCV感染敏感的特异手段.HCV RNA定量检测可用于血液及血液制品安全性监测、HCV发病机制及预后的研究、诊断病情及抗HCV治疗的疗效评价等.我们采用实时荧光定量PCR(FQ-PCR)检测49例丙肝患者血清HCV RNA,并与ELISA夹心法测定抗一HCV的结果相比较,以便更好地监测HCV的感染,并及时进行抗病毒治疗.

  17. 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.

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

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    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.

  19. Contribution of donor age to the recent decrease in patient survival among HCV-infected liver transplant recipients.

    Science.gov (United States)

    Berenguer, Marina; Prieto, Martín; San Juan, Fernando; Rayón, José M; Martinez, Fernando; Carrasco, Domingo; Moya, Angel; Orbis, Francisco; Mir, José; Berenguer, Joaquín

    2002-07-01

    Recurrent hepatitis occurs in the majority of patients undergoing liver transplantation for hepatitis C virus (HCV) cirrhosis, with progression to cirrhosis in up to 30% after 5 years. Based on these data, a decrease in survival can be anticipated with prolonged follow-up. Furthermore, posttransplantation HCV-fibrosis progression has been shown in recent years to increase. Our aims were (1) to describe the natural history of HCV-infected recipients, particularly to determine whether survival has decreased in recent years; (2) to compare this outcome with that observed in non-HCV-infected cirrhosis controls; and (3) to determine the factors associated with disease severity and survival. Among 522 cirrhotic patients undergoing transplantation between 1991 and 2000, 283 (54%) were infected with HCV. Yearly biopsies were performed in these recipients and at 1 and 5 years in the remainder. With similar follow-up, the percentage of deaths in the HCV(+) group was significantly higher than in the HCV- group (37% vs. 22%, P <.001), and patient survival was lower (77%, 61%, 55% vs. 87%, 76%, 70% at 1, 5, and 7 years, respectively; P =.0001). Although survival has increased in the HCV- group in recent years, it has significantly decreased in HCV recipients (P <.0001). The main cause of death among the latter was decompensated graft cirrhosis (n = 23/105, 22%), whereas that of HCV- patients was infections (n = 10/52, 19%). Reasons for the recent worse outcome in HCV+ recipients include the increased donor age and stronger immunosuppression. In conclusion, patient survival is lower among HCV+ recipients than among HCV- ones and has been decreasing in recent years. The aging of donors is a major contributor to this worse outcome.

  20. Analysis of false positive detection of HCV antibody by ELISA%HCV抗体ELISA检测假阳性分析

    Institute of Scientific and Technical Information of China (English)

    张力; 张文娟

    2014-01-01

    Objective To discuss the false positive problem when the S/CO mean of HCV Ab test by ELISA is between 1 to 3.8. Methods 26 cases whose first S/CO mean(3 times by ELISA) was between 1 to 3.8 and 20 cases of normal healthy people were chosen. Do blood test again from 2 months to 6 months. Results 6 cases among 26 cases of reactive result of first ELISA tested negative in the second experiment.20 normal individuals tested negative twice by ELISA.There is significance difference between two test(P<0.01). Conclusion If detection of HCV Ab by ELISA is reactive,should be regularly reviewed,or do other tests.%目的:探讨HCV抗体ELISA检测1<S/CO均值<3.8时假阳性问题。方法筛选HCV抗体ELISA首次检测1<S/CO(3次均值)<3.8共26例,正常体检人群20例,2~6月之间再次抽血检测。结果26例首次检测ELISA有反应性其中6例再次检测为阴性,最终该6例患者确诊为阴性,20例正常体检人群2次均为阴性。两次检测比较结果有显著性差异(P<0.01)。结论 HCV抗体ELISA检测有反应性时应定期复查或做其它检测。

  1. Injection drug use is a risk factor for HCV infection in urban Egypt.

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    Adela Paez Jimenez

    Full Text Available OBJECTIVE: To identify current risk factors for hepatitis C virus (HCV transmission in Greater Cairo. DESIGN AND SETTING: A 1:1 matched case-control study was conducted comparing incident acute symptomatic hepatitis C patients in two "fever" hospitals of Greater Cairo with two control groups: household members of the cases and acute hepatitis A patients diagnosed at the same hospitals. Controls were matched on the same age and sex to cases and were all anti-HCV antibody negative. Iatrogenic, community and household exposures to HCV in the one to six months before symptoms onset for cases, and date of interview for controls, were exhaustively assessed. RESULTS: From 2002 to 2007, 94 definite acute symptomatic HCV cases and 188 controls were enrolled in the study. In multivariate analysis, intravenous injections (OR = 5.0; 95% CI = 1.2-20.2, medical stitches (OR = 4.2; 95% CI = 1.6-11.3, injection drug use (IDU (OR = 7.9; 95% CI = 1.4-43.5, recent marriage (OR = 3.3; 95% CI = 1.1-9.9 and illiteracy (OR = 3.9; 95% CI = 1.8-8.5 were independently associated with an increased HCV risk. CONCLUSION: In urban Cairo, invasive health care procedures remain a source of HCV transmission and IDU is an emerging risk factor. Strict application of standard precautions during health care is a priority. Implementation of comprehensive infection prevention programs for IDU should be considered.

  2. 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.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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

  8. Altered metal metabolism in patients with HCV-related cirrhosis and hepatic encephalopathy.

    Science.gov (United States)

    Marano, Massimo; Vespasiani Gentilucci, Umberto; Altamura, Claudia; Siotto, Mariacristina; Squitti, Rosanna; Bucossi, Serena; Quintiliani, Livia; Migliore, Simone; Greco, Federico; Scarciolla, Laura; Quattrocchi, Carlo Cosimo; Picardi, Antonio; Vernieri, Fabrizio

    2015-12-01

    Dysfunctional metal homeostasis contributes to oxidative stress and neuronal damage. These have been implicated in hepatic encephalopathy pathogenesis. To investigate whether altered metal metabolism is associated with hepatic encephalopathy. Twenty-one controls and 34 HCV-cirrhotic patients (ENC/NEC patients according to presence/absence of previous overt episodes of hepatic encephalopathy) and a control group were studied. Serum iron, copper, ceruloplasmin, ceruloplasmin activity, transferrin, and ceruloplasmin/transferrin ratio were determined. Neuropsychological tests were performed by the repeatable battery of neuropsychological status. Magnetic resonance assessed basal ganglia volumes and metal deposition (pallidal index and T2*). Cirrhotic patients performed worse than controls at cognitive tests, especially ENC patients,. At biochemical analysis copper concentrations, ceruloplasmin activity and transferrin levels were lower in ENC than in NEC patients and controls (p < 0.05 and p < 0.01, respectively). Ceruloplasmin/transferrin ratio was higher in ENC compared to NEC patients (p < 0.05), and controls (p < 0.01). By brain magnetic resonance, ENC patients showed reduced caudate and globus pallidus volumes compared to controls (p < 0.05), and ENC and NEC patients an increased pallidal index compared to controls (p < 0.01). In ENC patients, ceruloplasmin activity correlated with caudate volume and pallidal index (ρ = 0.773 and ρ = -0.683, p < 0.05). Altered metal metabolism likely contributes to cirrhotic hepatic encephalopathy. PMID:26307419

  9. 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.

  10. FAT10 suppression stabilizes oxidized proteins in liver cells: Effects of HCV and ethanol.

    Science.gov (United States)

    Ganesan, Murali; Hindman, Joseph; Tillman, Brittany; Jaramillo, Lee; Poluektova, Larisa I; French, Barbara A; Kharbanda, Kusum K; French, Samuel W; Osna, Natalia A

    2015-12-01

    FAT10 belongs to the ubiquitin-like modifier (ULM) family that targets proteins for degradation and is recognized by 26S proteasome. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by IFNγ and TNFα in the non-immune (liver parenchymal) cells. It is not clear how viral proteins and alcohol regulate FAT10 expression on liver cells. In this study, we aimed to investigate whether FAT10 expression on liver cells is activated by the innate immunity factor, IFNα and how HCV protein expression in hepatocytes and ethanol-induced oxidative stress affect the level of FAT10 in liver cells. For this study, we used HCV(+) transgenic mice that express structural HCV proteins and their HCV(-) littermates. Mice were fed Lieber De Carli diet (control and ethanol) as specified in the NIH protocol for chronic-acute ethanol feeding. Alcohol exposure enhanced steatosis, induced oxidative stress and decreased proteasome activity in the liversof these mice, with more robust response to ethanol in HCV(+) mice. IFNα induced transcriptional activation of FAT10 in liver cells, which was dysregulated by ethanol feeding. Accordingly, IFNα-activated expression of FAT10 in hepatocytes (measured by indirect immunofluorescent of liver tissue) was also suppressed by ethanol exposure in both HCV(+) and HCV(-) mice. This suppression was accompanied with ethanol-mediated induction of lipid peroxidation marker, 4-HNE. All aforementioned effects of ethanol were attenuated by in vivo feeding of mice with the pro-methylating agent, betaine, which exhibits strong anti-oxidant properties. Based on this study, we hypothesize that FAT10 targets oxidatively modified proteins for proteasomal degradation, and that the reduction in FAT10 levels along with decreased proteasome activity may contribute to stabilization of these altered proteins in hepatocytes. In conclusion, IFNα induced FAT10 expression, which is suppressed by ethanol feeding in both HCV

  11. 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.

  12. 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

  13. HCV quasispecies evolution during treatment with interferon alfa-2b and ribavirin in two children coinfected with HCV and HIV-1.

    Science.gov (United States)

    Quesnel-Vallières, Mathieu; Lemay, Mireille; Lapointe, Normand; Martin, Steven R; Soudeyns, Hugo

    2008-10-01

    Two children who acquired hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infection by mother-to-child transmission were monitored during interferon alfa-2b and ribavirin treatment. In Patient C1, CD4(+) T cell counts were within normal range and HIV-1 viral load was undetectable. HCV viral load declined slightly following treatment initiation while novel variants rapidly emerged, indicative of quasispecies diversification. In Patient C2, CD4(+) T cell counts were low and HIV-1 replication was not fully controlled by antiretroviral therapy. HCV viral load rose during treatment and a striking conservation of the variant spectrum was observed. In both cases, there was no decline in quasispecies complexity following treatment initiation and sustained virological response was not achieved. These results suggest that reduction in quasispecies complexity, which is observed in adult responders following interferon treatment, may be mechanistically unrelated with evolution of the variant profile and/or selective pressure exerted on HCV. PMID:18707918

  14. Direct binding of ledipasvir to HCV NS5A: mechanism of resistance to an HCV antiviral agent.

    Directory of Open Access Journals (Sweden)

    Hyock Joo Kwon

    Full Text Available Ledipasvir, a direct acting antiviral agent (DAA targeting the Hepatitis C Virus NS5A protein, exhibits picomolar activity in replicon cells. While its mechanism of action is unclear, mutations that confer resistance to ledipasvir in HCV replicon cells are located in NS5A, suggesting that NS5A is the direct target of ledipasvir. To date co-precipitation and cross-linking experiments in replicon or NS5A transfected cells have not conclusively shown a direct, specific interaction between NS5A and ledipasvir. Using recombinant, full length NS5A, we show that ledipasvir binds directly, with high affinity and specificity, to NS5A. Ledipasvir binding to recombinant NS5A is saturable with a dissociation constant in the low nanomolar range. A mutant form of NS5A (Y93H that confers resistance to ledipasvir shows diminished binding to ledipasvir. The current study shows that ledipasvir inhibits NS5A through direct binding and that resistance to ledipasvir is the result of a reduction in binding affinity to NS5A mutants.

  15. 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

  16. [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.

  17. 献血者抗-HCV不合格标本RIBA确认结果分析%The RIBA Confirmation of Anti-HCV ELISA Positive Samples from Blood Donors

    Institute of Scientific and Technical Information of China (English)

    钱立琼; 蹇志伟; 谭金旭

    2013-01-01

    Objective To analyze the results of RIBA confirmation for anti-HCV ELISA positive samples from blood donors,and to study the combination of anti-HCV ELISA reagents and the setting of grey area.Methods A total of 113 anti-HCV positive sample identified by ELISA were tested by using the restructuring immune imprinting(RIBA).Resuits Forty-six samples(40.7%,46/113)were confirmed positive by RIBA,41 samples were uncertain,and 26 samples were negative.Among the 46 RIBA confirmed HCV positive samples,the test results of 2 kinds of anti-HCV ELISA reagents were both positive for 44 samples.The 2 samples were positive with only one of reagents,others were negative or uncertain.Among the specimens with anti-HCV results in the grey area,the RIBA confirmation showed either uncertain or negative.In the anti-HCV positive samples identified by 2 ELISA reagents,the rate of confirmed positivity was 83.0%.Conclusion For ensuring the safety of blood,it's very important to use combination of the domestic and overseas antiHCV ELISA reagents and to set a proper grey area.%目的 分析献血人群ELISA试剂抗-HCV不合格标本确认结果,探讨抗-HCV ELISA试剂组合及灰区限的设置.方法 收集113份ELISA试剂抗-HCV不合格标本,采用重组免疫印迹实验(RIBA)进行确认,并比较不同ELISA试剂的检测情况.结果 113份ELISA检测不合格标本中,RIBA确认阳性46份,不确定39份,阴性28份.确认阳性比例为40.7%.RIBA确认阳性的标本中,2种抗-HCV ELISA试剂检测结果均呈阳性反应的有44份;1种抗-HCV ELISA试剂呈阳性反应的标本中,RIBA确认阳性有2份,其余为阴性或不确定;灰区标本中,确认结果均为不确定或阴性.2种ELISA试剂检测均呈阳性反应的标本中,确认阳性率为78.57%.结论 选用国产和进口试剂相组合,并设定灰区限,对保证血液安全意义重大.

  18. INVESTIGATION AND ANALYSIS OF INFECTION WITH HIV, HCV, SYPHILIS AND HSV-2 FOR METHADONE DRUG USERS IN LESHAN CITY%乐山市美沙酮门诊吸毒人群HIV、HCV、梅毒和HSV-2感染状况调查分析

    Institute of Scientific and Technical Information of China (English)

    牟怀德; 陈霞; 吴薇; 刘昕亮; 谢应国; 李娜

    2011-01-01

    [Objective] To investigation the HIV, HCV, syphilis and HSV-2 infection of methadone drug users in Le-shan city. [Methods] Collected 618 methadone drug users' blood in three cities and counties to test HIV, HCV, syphilis and HSV-2 antibody, and analysed the test results. [ Results] The positive rate of HIV antibody of 618 drug users was 10.84%, positive rate HCV antibody was 71.84%, positive rate of syphilis antibody was 4.85%; positive rates of HIV antibody and HCV antibody in three methadone drug users were significantly different (χ2 = 9.43, P = 0.01;χ2 = 29.75, P = 0.00); the positive rates of HCV antibody in all age groups were significantly different (χ2 = 5.23, P =0.00); the combined infection rate of HIV/ HCV was 5.18%, combined infection rate of HTV/HCV/syphilis 0.16%, the combined infection rate of HCV/syphilis 3.56%. The positive rate of HSV-2 antibody in 67 cases of HIV infection was 61.19% , the combined infection rate of HIV/HCV/ syphilis/HSV-2 herpes was 1.49%, the combined infection rate of HIV/HCV/HSV-2 herpes was 52.24%. [Conclusion] The infection rates of HIV, HCV, syphilis and HSV-2 in methadone drug users are higher, and infections are serious in Leshan city. We should actively carry out health education and take appropriate intervention measures.%[目的]了解乐山市美沙酮门诊吸毒人群HIV、HCV、梅毒和HSV -2感染状况.[方法]采集乐山市3个区市(县)的美沙酮门诊618名吸毒人员的静脉血进行HIV、HCV、梅毒以及HSV -2血清抗体检测,并对检测结果进行分析.[结果]618名吸毒人员HIV抗体阳性率为10.84%,HCV抗体阳性率为71.84%,梅毒抗体阳性率为4.85%;3个美沙酮门诊吸毒人员HIV抗体阳性率以及HCV抗体阳性率差异有统计学意义(f=9.43,P=0.01;x2=29.75,P=0.00);各年龄段间HCV抗体阳性率差异有统计学意义(x2=5.23,P=0.00);HIV/HCV合并感染率为5.18%、HIV/HCV/梅毒合并感染率为0.16%、HCV/梅毒合并感染率为3.56

  19. Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1

    Science.gov (United States)

    Naggie, Susanna; Cooper, Curtis; Saag, Michael; Workowski, Kimberly; Ruane, Peter; Towner, William J.; Marks, Kristen; Luetkemeyer, Anne; Baden, Rachel P.; Sax, Paul E.; Gane, Edward; Santana-Bagur, Jorge; Stamm, Luisa M.; Yang, Jenny C.; German, Polina; Dvory-Sobol, Hadas; Ni, Liyun; Pang, Phillip S.; McHutchison, John G.; Stedman, Catherine A.M.; Morales-Ramirez, Javier O.; Bräu, Norbert; Jayaweera, Dushyantha; Colson, Amy E.; Tebas, Pablo; Wong, David K.; Dieterich, Douglas; Sulkowski, Mark

    2016-01-01

    BACKGROUND Effective treatment for hepatitis C virus (HCV) in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains an unmet medical need. METHODS We conducted a multicenter, single-group, open-label study involving patients coinfected with HIV-1 and genotype 1 or 4 HCV receiving an antiretroviral regimen of tenofovir and emtricitabine with efavirenz, rilpivirine, or raltegravir. All patients received ledipasvir, an NS5A inhibitor, and sofosbuvir, a nucleotide polymerase inhibitor, as a single fixed-dose combination for 12 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS Of the 335 patients enrolled, 34% were black, 55% had been previously treated for HCV, and 20% had cirrhosis. Overall, 322 patients (96%) had a sustained virologic response at 12 weeks after the end of therapy (95% confidence interval [CI], 93 to 98), including rates of 96% (95% CI, 93 to 98) in patients with HCV genotype 1a, 96% (95% CI, 89 to 99) in those with HCV genotype 1b, and 100% (95% CI, 63 to 100) in those with HCV genotype 4. Rates of sustained virologic response were similar regardless of previous treatment or the presence of cirrhosis. Of the 13 patients who did not have a sustained virologic response, 10 had a relapse after the end of treatment. No patient had confirmed HIV-1 viro-logic rebound. The most common adverse events were headache (25%), fatigue (21%), and diarrhea (11%). No patient discontinued treatment because of adverse events. CONCLUSIONS Ledipasvir and sofosbuvir for 12 weeks provided high rates of sustained virologic response in patients coinfected with HIV-1 and HCV genotype 1 or 4. (Funded by Gilead Sciences; ION-4 ClinicalTrials.gov number, NCT02073656.) PMID:26196665

  20. Finally sofosbuvir: an oral anti-HCV drug with wide performance capability

    Directory of Open Access Journals (Sweden)

    Kayali Z

    2014-12-01

    Full Text Available Zeid Kayali,1 Warren N Schmidt2,3 1Division of Gastroenterology and Hepatology, University of Southern California, Los Angeles, CA, USA; 2Department of Internal Medicine and Research Service, Veterans Affairs Medical Center, Iowa City, IA, USA; 3Roy G and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA, USA Abstract: Chronic Hepatitis C virus (HCV infection is the leading cause of advanced liver disease worldwide. The virus successfully evades host immune detection and for many years has hampered efforts to find a safe, uncomplicated, and reliable oral antiviral therapy. Initially, interferon and ribavirin therapy was the treatment standard of care, but it offered limited performance across the wide spectrum of HCV disease and was fraught with excessive and often limiting side effects. Sofosbuvir (SOF is a potent first-in-class nucleoside inhibitor that has recently been approved for treatment of HCV. The drug has low toxicity, a high resistance barrier, and minimal drug interactions with other HCV direct-acting antiviral agents such as protease inhibitors or anti-NS5A agents. SOF is safe and can be used across different viral genotypes, disease stages, and special patient groups, such as those coinfected with human immunodeficiency virus. When used in combination with ribavirin or another direct-acting antiviral agent, SOF has revolutionized the HCV treatment spectrum and set the stage for nearly universal HCV antiviral therapy. More so than any other anti-HCV drug developed to date, SOF offers the widest applicability for all infected patients, and new regimens will be tailored to maximize performance. Keywords: Hepatitis C virus, sofosbuvir, polymerase inhibitors, interferon-free treatment

  1. 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.

  2. 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 ...

  3. Interferon (IFN) and Cellular Immune Response Evoked in RNA-Pattern Sensing During Infection with Hepatitis C Virus (HCV).

    Science.gov (United States)

    Nakai, Masato; Oshiumi, Hiroyuki; Funami, Kenji; Okamoto, Masaaki; Matsumoto, Misako; Seya, Tsukasa; Sakamoto, Naoya

    2015-01-01

    Hepatitis C virus (HCV) infects hepatocytes but not dendritic cells (DCs), but DCs effectively mature in response to HCV-infected hepatocytes. Using gene-disrupted mice and hydrodynamic injection strategy, we found the MAVS pathway to be crucial for induction of type III interferons (IFNs) in response to HCV in mouse. Human hepatocytes barely express TLR3 under non-infectious states, but frequently express it in HCV infection. Type I and III IFNs are induced upon stimulation with polyI:C, an analog of double-stranded (ds)RNA. Activation of TLR3 and the TICAM-1 pathway, followed by DC-mediated activation of cellular immunity, is augmented during exposure to viral RNA. Although type III IFNs are released from replication-competent human hepatocytes, DC-mediated CTL proliferation and NK cell activation hardly occur in response to the released type III IFNs. Yet, type I IFNs and HCV-infected hepatocytes can induce maturation of DCs in either human or mouse origin. In addition, mouse CD8+ DCs mature in response to HCV-infected hepatocytes unless the TLR3/TICAM-1 pathway is blocked. We found the exosomes containing HCV RNA in the supernatant of the HCV-infected hepatocytes act as a source of TLR3-mediated DC maturation. Here we summarize our view on the mechanism by which DCs mature to induce NK and CTL in a status of HCV infection.

  4. 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

  5. A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes

    Science.gov (United States)

    Qian, Xi-Jing; Zhang, Xiao-Lian; Zhao, Ping; Jin, Yong-Sheng; Chen, Hai-Sheng; Xu, Qing-Qiang; Ren, Hao; Zhu, Shi-Ying; Tang, Hai-Lin; Zhu, Yong-Zhe; Qi, Zhong-Tian

    2016-01-01

    Despite recent progress in the development of hepatitis C virus (HCV) inhibitors, cost-effective antiviral drugs, especially among the patients receiving liver transplantations, are still awaited. Schisandra is a traditional medicinal herb used to treat a range of liver disorders including hepatitis for thousands of years in China. To isolate the bioactive compounds of schisandra for the treatment of HCV infection, we screened a schisandra-extracts library and identified a tetracyclic triterpenoid, schizandronic acid (SZA), as a novel HCV entry inhibitor. Our findings suggested that SZA potently inhibited pan-HCV genotype entry into hepatoma cells and primary human hepatocytes without interfering virus binding on cell surface or internalization. However, virion-cell fusion process was impaired in the presence of SZA, along with the increased host membrane fluidity. We also found that SZA inhibited the spread of HCV to the neighboring cells, and combinations of SZA with interferon or telaprevir resulted in additive synergistic effect against HCV. Additionally, SZA diminished the establishment of HCV infection in vivo. The SZA target is different from conventional direct-acting antiviral agents, therefore, SZA is a potential therapeutic compound for the development of effective HCV entry inhibitors, especially for patients who need to prevent HCV reinfection during the course of liver transplantations. PMID:27252043

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

    Science.gov (United States)

    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. Healthy controls were subjects participating in medical checkups. Conditional logistic regression models were used. Results A total of 234 matched-case and patient- and healthy-control pairs were analyzed. The significant risk factors for both controls were sharing razors (adjusted odds ratio [aOR], 2.39 and 3.29, respectively) and having more than four lifetime sexual partners (aOR, 2.15 and 6.89, respectively). Contact dockworkers (aOR, 1.91) and tattoos (aOR, 2.20) were significant risk factors for the patient controls. Transfusion (aOR, 5.38), a bloody operation (aOR, 5.02), acupuncture (aOR, 2.08), and piercing (aOR, 5.95) were significant risk factors for the healthy controls. Needle stick injuries and intravenous drug abuse were significant in the univariate analysis. Conclusions More education concerning the dangers of sharing razors, tattoos and piercings is required to prevent HCV infection. More attention should be paid to needle stick injuries in hospitals and the community. PMID:26260752

  7. 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 gen