Hepatitis: Chevaliez S

Chevaliez S, Pawlotsky JM. · Department of Virology, Hopital Henri Mondor, Universite Paris 12, Creteil, France. · Ann Hepatol. · Pubmed #19221527 No free full text.

This publication has no abstract.

Chevaliez S, Pawlotsky JM. · Department of Virology & INSERM U841, French National Reference Center for Viral Hepatitis B, C and delta, Hôpital Henri Mondor, Université Paris 12, Créteil, France. · Liver Int. · Pubmed #19207960 No free full text.

Abstract: Chronic hepatitis C is a global health problem that may cause cirrhosis and progression to hepatocellular carcinoma. Currently available antiviral treatments are moderately effective. Several virological assays are available to help diagnose and manage patients infected with the hepatitis C virus (HCV). These include the anti-HCV antibody assays, measurement of HCV RNA viral load and HCV genotyping. HCV RNA can be assayed by two types of molecular biology-based techniques: target amplification as in polymerase chain reaction methods and signal amplification such as the branched DNA assay. Monitoring of viral kinetics during the early phases of antiviral treatment is crucial in making treatment decisions such as early stopping rules and also in optimizing the length of treatment. The HCV genotype can be determined by several methods. Whatever the method, pretreatment determination allows treatment length and ribavirin dose to be optimized and also offers prognostic information on treatment outcomes as certain genotypes respond more favourably to treatment. Thus, virological assays are indispensable in the diagnosis and management of individuals infected with the HCV.

Chevaliez S, Pawlotsky JM. · Department of Virology & INSERM U955, French National Reference Centre for Viral Hepatitis B, C and delta, Hôpital Henri Mondor, Université Paris, Créteil, France. · Best Pract Res Clin Gastroenterol. · Pubmed #19187865 No free full text.

Abstract: Virological tools, including serological and molecular tools, are needed to diagnose chronic hepatitis B and C infections. They may also be useful to establish their prognosis, but they have found their principal application in guiding treatment decisions and assessing the virological responses to therapy. The goal of chronic hepatitis B therapy is to prevent progression of liver disease. This is achieved if HBV replication is durably abolished or significantly reduced. In HBeAg-positive patients, HBeAg clearance followed by the HBe seroconversion phase can be achieved. In HBeAg-negative patients, long-term antiviral suppression of viral replication is needed. The loss of HBsAg, eventually associated with an HBs seroconversion, is the most desirable endpoint of therapy but is rarely achieved. The efficacy endpoint of chronic hepatitis C treatment is the sustained virological response, defined by an undetectable HCV RNA in serum with a sensitive assay 24 weeks after the end of treatment. The HCV genotype and on-treatment viral kinetics can be used to tailor treatment dosages and duration.

Chevaliez S, Pawlotsky JM. · French National Reference Center for Viral Hepatitis B, C and delta, Department of Virology, Hôpital Henri Mondor, 51 avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France. · Handb Exp Pharmacol. · Pubmed #19048202 No free full text.

Abstract: In 2007, the world celebrated the 50th anniversary of the discovery of interferon (IFN) by Isaacs and Lindenmann. Subsequently, the IFN-alpha gene was cloned, fully sequenced and IFN-alpha was produced in recombinant form. Recombinant IFN-alpha is now used as the basis for treatment of chronic hepatitis C virus infection and can also be used to treat certain forms of chronic hepatitis B virus infections. IFNs have also been used in other viral infections, although with less success. The antiviral mechanisms of IFNs are reviewed in this chapter as well as the utility of IFNs in the treatment of persistent viral infections.

Chevaliez S, Pawlotsky JM. · Department of Virology, Henri Mondor Hospital, University of Paris XII, Paris, France. · J Viral Hepat. · Pubmed #17958647 No free full text.

Abstract: Prevention of hepatitis C virus (HCV) infection complications can be achieved by antiviral therapy based on the use of a combination of pegylated interferon (IFN)-alpha and ribavirin. The steady-state kinetics of HCV infection represents the treatment target. The goal is cure, which is achieved when all infected cells have been cleared from the body. Because of their intrinsic properties, real-time polymerase chain reaction (PCR) methods are rapidly replacing other technologies for routine quantification of HCV-RNA during antiviral therapy. The virological response at week 12 of therapy is currently used to tailor treatment duration in HCV genotype 1 infection only. Recent reports suggest that the virological response at week 4 could be used to tailor treatment duration, whatever the HCV genotype.

Chevaliez S, Pawlotsky JM. · French National Reference Center for Viral Hepatitis B, C and delta, Department of Virology, Hôpital Henri Mondor, Université Paris 12, Créteil, France. · Adv Drug Deliv Rev. · Pubmed #17869375 No free full text.

Abstract: In 2007, the world celebrated the 50th anniversary of the discovery of interferon (IFN). The first clinical trial of recombinant IFN-alpha in patients with chronic hepatitis C was published in 1986. This article reviews the classification of IFNs, IFN production during viral infections, IFN signaling pathways and the mechanisms of their antiviral and immunomodulatory properties. Hepatitis C virus infection treatment is currently based on the combination of pegylated IFN-alpha and ribavirin. The pegylated IFN-alpha molecules are described, as well as the putative mechanisms of action of ribavirin. Current treatment guidelines are discussed and new results suggesting that the treatment schedule should be tailored to the early virological response during therapy are presented. Finally, insights into new hepatitis C drug developments are given.

Chevaliez S, Pawlotsky JM. · French National Reference Center for Viral Hepatitis B, C and delta, Department of Virology & INSERM U 841, Hopital Henri Mondor, 94010 Creteil, France. · World J Gastroenterol. · Pubmed #17552030 links to  free full text

Abstract: Hepatitis C virus (HCV) infects approximately 170 million individuals worldwide. Prevention of HCV infection complications is based on antiviral therapy with the combination of pegylated interferon alfa and ribavirin. The use of serological and virological tests has become essential in the management of HCV infection in order to diagnose infection, guide treatment decisions and assess the virological response to antiviral therapy. Anti-HCV antibody testing and HCV RNA testing are used to diagnose acute and chronic hepatitis C. 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.

Pawlotsky JM, Chevaliez S, McHutchison JG. · French National Reference Center for Viral Hepatitis B, C, and delta, Department of Virology, Hôpital Henri Mondor, Université Paris 12, Créteil, France. · Gastroenterology. · Pubmed #17484890 No free full text.

Abstract: The burden of disease consequent to hepatitis C virus (HCV) infection has been well described and is expected to increase dramatically over the next decade. Current approved antiviral therapies are effective in eradicating the virus in approximately 50% of infected patients. However, pegylated interferon and ribavirin-based therapy is costly, prolonged, associated with significant adverse effects, and not deemed suitable for many HCV-infected patients. As such, there is a clear and pressing need for the development of additional agents that act through alternate or different mechanisms, in the hope that such regimens could lead to enhanced response rates more broadly applicable to patients with hepatitis C infection. Recent basic science enhancements in HCV cell culture systems and replication assays have led to a broadening of our understanding of many of the mechanisms of HCV replication and, therefore, potential novel antiviral targets. In this article, we have attempted to highlight important new information as it relates to our understanding of the HCV life cycle. These steps broadly encompass viral attachment, entry, and fusion; viral RNA translation; posttranslational processing; HCV replication; and viral assembly and release. In each of these areas, we present up-to-date knowledge of the relevant aspects of that component of the viral life cycle and then describe the preclinical and clinical development targets and pathways being explored in the translational and clinical settings.

Chevaliez S, Pawlotsky JM. · Department of Virology, INSERM U635, Henri Mondor Hospital, University of Paris XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France. · Clin Liver Dis. · Pubmed #16023971 No free full text.

Abstract: This article discusses the use of virologic assays in the diagnosis and management of hepatitis C virus (HCV) infection. The use of virologic tests has become essential in the management of HCV infection to diagnose HCV infection, guide treatment decisions, and assess the virologic response to antiviral therapy. The continuing development of test systems accompanied by new antiviral drugs and novel therapeutic approaches should lead to an optimization of the treatment of HCV infection.

Chevaliez S, Pawlotsky JM. · Laboratoire de virologie, Inserm U635, hôpital Henri Mondor, Université Paris 12, 94010 Créteil Cedex. · Rev Prat. · Pubmed #15913113 No free full text.

Abstract: The virological diagnosis of viral hepatitis is based on the study of direct markers (viral antigens and genomes) and indirect markers (specific antibodies). The diagnosis of hepatitis B is based on the interpretation of antigen-antibody profiles and, for chronic hepatitis B, on HBV DNA detection. Treatment responses are assessed by the HBe seroconversion in HBe antigen-positive patients, and by measuring HBV DNA levels. The diagnosis of hepatitis C is based on the detection of anti-HCV antibodies and HCV RNA by means of molecular techniques. HCV genotype determination is used to tailor the treatment schedule to the individual patient. Treatment efficacy is assessed by means of molecular techniques to prove progressive and definitive viral clearance.

Hézode C, Chevaliez S, Bouvier-Alias M, Roudot-Thoraval F, Brillet R, Zafrani ES, Dhumeaux D, Pawlotsky JM. · Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris XII, Créteil, France. · J Hepatol. · Pubmed #17321635 No free full text.

Abstract: BACKGROUND/AIMS: Some patients receiving adefovir at the approved dose of 10 mg daily for chronic hepatitis B have a "suboptimal" virological response characterized by a slow and moderate decrease in viral replication. METHODS: We assessed the efficacy and safety of adefovir 20 mg daily in patients with hepatitis B e antigen-positive chronic hepatitis B resistant to lamivudine and a suboptimal virological response to adefovir 10 mg daily add-on. RESULTS: No amino acid substitutions known to confer adefovir resistance were found in these patients. In the five treated patients, the switch from 10 mg to 20 mg of adefovir daily significantly improved antiviral efficacy (-1.78+/-0.28 log international units/mL versus -3.73+/-0.51 log international units/mL, respectively, p=0.0039), and alanine aminotransferase levels normalized in all but one of the patients. No signs of renal dysfunction occurred. CONCLUSIONS: These results suggest: (i) that suboptimal responses to adefovir 10 mg daily are due to underdosing; and (ii) that increasing the adefovir dose to 20 mg daily is beneficial and safe in patients with lamivudine-resistant HBV and a suboptimal response to adefovir 10 mg daily, especially when alanine aminotransferase levels are elevated and/or the liver disease is severe or rapidly progressive. Careful monitoring of renal function is necessary.

Chevaliez S, Bouvier-Alias M, Pawlotsky JM. · French National Reference Center for Viral Hepatitis B, C, and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris 12, and INSERM U955, 94010 Créteil, France. · J Clin Microbiol. · Pubmed #19369435 No free full text.

Abstract: Quantification of hepatitis C virus (HCV) RNA is essential for the everyday management of chronic hepatitis C therapy. "Real-time" PCR techniques are potentially more sensitive than classical PCR techniques, are not prone to carryover contamination, and have a consistently wider dynamic range of quantification. Thus, they are rapidly replacing other technologies for routine quantification of HCV RNA. We extensively evaluated the intrinsic characteristics and clinical performance of the m2000(sp)-m2000(rt) Abbott real-time PCR platform for HCV RNA quantification. The study shows that the m2000(sp)-m2000(rt) platform is sensitive, specific, and precise; that the results are reproducible; and that the platform has a broad dynamic range of quantification. When comparing HCV RNA levels measured in the same individuals with the m2000(sp)-m2000(rt) platform and the third-generation branched-DNA assay, a trend toward a modest overestimation of HCV RNA levels was observed in the m2000(sp)-m2000(rt) platform in all genotypes except genotype 5. The differences, however, were unlikely to have any impact in clinical practice. In conclusion, our study shows that the Abbott m2000 real-time PCR system for HCV RNA quantification is sensitive, specific, and precise; that the results are reproducible; and that the platform's broad dynamic range of quantification is well suited to HCV RNA monitoring in the clinical setting.

Morice Y, Ratinier M, Miladi A, Chevaliez S, Germanidis G, Wedemeyer H, Laperche S, Lavergne JP, Pawlotsky JM. · National Reference Center for Viral Hepatitis B, C, and delta, Department of Virology, Henri Mondor Hospital, University of Paris 12, Créteil, France. · Hepatology. · Pubmed #19350656 No free full text.

Abstract: The existence of hepatitis C virus (HCV) proteins encoded by alternate reading frames overlapping the core-encoding region has been suggested. Several mechanisms of production have been postulated, and the functions of these proteins in the HCV life cycle remain unknown. We analyzed cases of seroconversion to an alternate reading frame protein in a group of 17 patients infected by one of the two HCV genotype 1b strains during an outbreak in a hemodialysis unit. Three patients seroconverted, and antibodies were transiently detected in another patient. Three of these patients were infected by one of the two HCV strains, whereas the strain infecting the remaining patient could not be identified. Quasispecies sequence analysis of the core-coding region showed no differences in the core or +1 reading frame sequences that could explain alternate reading frame protein seroconversion in some but not all of the patients infected by one of the HCV strains, and no such difference was found between the two strains. Because differences in the structure of RNA elements could play a role in frameshift events, we conducted a predictive analysis of RNA folding. No difference was found between the patients who did and did not seroconvert to alternate reading frame protein. Conclusion: Our findings prove that alternate reading frame proteins can be produced during acute HCV infection. However, seroconversion does not occur in all patients for unknown reasons. Alternate reading frame protein could be generated by minority quasispecies variants or variants that occur transiently.

Challine D, Chevaliez S, Pawlotsky JM. · Department of Virology, French National Reference Center for Viral Hepatitis B, C and Delta, Hôpital Henri Mondor, Université Paris 12, Créteil, France. · Gastroenterology. · Pubmed #18694749 No free full text.

Abstract: BACKGROUND & AIMS: Screens for serologic markers of hepatitis B virus (HBV) are used to prevent its transmission through transplantation. However, exclusion of noninfectious seropositive donors exacerbates graft shortages, and a residual risk of transmission by seronegative donors also exists. This study assessed the risk of HBV associated with different HBV serologic profiles in organ, tissue, and cell transplants, as well as the risk of HBV transmission from seronegative donors. METHODS: A total of 11,155 consecutive organ, tissue, and cell donors were screened for HBV serologic markers. HBV DNA was screened for in 626 donors with at least one HBV serologic marker and 1433 multiple organ donors who were HBV seronegative or had anti-hepatitis B surface antigens (HBs) antibodies alone. RESULTS: HBV DNA was detected in most HBs-antigen-positive donors, but HBV-DNA levels were considerably lower than in patients with chronic hepatitis B. HBV DNA also was found in organ and cornea donors without HBs antigen. The prevalence of HBV DNA in organ donors with no HBV serologic markers or isolated anti-HBs antibodies was 0.07% (95% confidence interval, 0.01%-0.40%). One HBV-DNA-positive organ donor with isolated anti-HBs antibodies had amino acid substitutions in the hepatitis B surface antigen sequence. CONCLUSIONS: The analytic sensitivity of commercial hepatitis B surface antigen assays and their ability to detect HBsAg mutants should be improved. The utility and cost-efficacy ratio of systematic HBV-DNA testing should be assessed with the goal of excluding HBV-DNA-positive donations not identified through serologic testing while retaining donations that carry no risk of HBV transmission.

Girou E, Chevaliez S, Challine D, Thiessart M, Morice Y, Lesprit P, Tkoub-Scheirlinck L, Soing-Altrach S, Cizeau F, Cavin C, André M, Dahmanne D, Lang P, Pawlotsky JM. · Infection Control Unit, Henri Mondor Hospital, Créteil, France. · Clin Infect Dis. · Pubmed #18662134 No free full text.

Abstract: BACKGROUND: Nosocomial transmission is the second most frequent cause of hepatitis C virus (HCV) infection. A prospective observational study was conducted to assess the roles of environmental contamination and noncompliance with standard precautions in HCV cross-transmission in a hemodialysis unit. METHODS: Patients undergoing chronic hemodialysis in a French university hospital unit were systematically screened, revealing 2 sporadic cases of HCV transmission. An investigation was launched to determine whether the patients were infected in the hemodialysis unit and the possible roles of environmental contamination and noncompliance with standard precautions. We examined possible relationships among new cases of HCV infection, environmental contamination by blood and HCV RNA, and compliance with guidelines on hand hygiene and glove use. RESULTS: Two patients experienced seroconversion to HCV during the study period. Phylogenetic analyses showed that 1 of these patients was infected with the same strain as that affecting a chronically infected patient also treated in the unit. Of 740 environmental surface samples, 82 (11%) contained hemoglobin; 6 (7%) of those contained HCV RNA. The rate of compliance with hand hygiene was 37% (95% confidence interval, 35%-39%), and gloves were immediately removed after patient care in 33% (95% confidence interval, 29%-37%) of cases. A low ratio of nurses to patients and poor hand hygiene were independent predictors of the presence of hemoglobin on environmental surfaces. CONCLUSION: Blood-contaminated surfaces may be a source of HCV cross-transmission in a hemodialysis unit. Strict compliance with hand hygiene and glove use and strict organization of care procedures are needed to reduce the risk of HCV cross-transmission among patients undergoing hemodialysis.

Chevaliez S, Bouvier-Alias M, Laperche S, Pawlotsky JM. · French National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris 12. · J Clin Microbiol. · Pubmed #18287319 links to  free full text

Abstract: Hepatitis B virus (HBV) DNA quantification is used to establish the prognosis of chronic HBV-related liver disease, to identify those patients who need to be treated, and to monitor the virologic response and resistance to antiviral therapies. Real-time PCR-based assays are gradually replacing other technologies for routine quantification of HBV DNA in clinical practice. The goal of this study was to evaluate the intrinsic characteristics and clinical performance of the real-time PCR Cobas AmpliPrep/Cobas TaqMan (CAP/CTM) platform for HBV DNA quantification. Specificity was satisfactory (95% confidence interval, 98.1 to 100%). Intra-assay coefficients of variation ranged from 0.22% to 2.68%, and interassay coefficients of variation ranged from 1.31% to 4.13%. Quantification was linear over the full dynamic range of quantification of the assay (1.7 to 8.0 log(10) IU/ml) and was not affected by dilution. The assay was accurate regardless of the HBV genotype. Samples containing HBV DNA levels above 4.5 log(10) IU/ml were slightly underestimated relative to another accurate assay based on branched-DNA technology, but this is unlikely to have noteworthy clinical implications. Thus, the CAP/CTM HBV DNA assay is sensitive, specific, and reproducible, and it accurately quantifies HBV DNA levels in patients chronically infected by HBV genotypes A to F. Samples with HBV DNA concentrations above the upper limit of quantification need to be diluted and then retested. Broad use of fully automated real-time PCR assays should improve the management of patients with chronic HBV infection.

Chevaliez S, Bouvier-Alias M, Brillet R, Pawlotsky JM. · French National Reference Center for Viral Hepatitis B, C, and Delta, Department of Virology, Hôpital Henri Mondor, Créteil, France. · Hepatology. · Pubmed #17525931 No free full text.

Abstract: The quantification of hepatitis C virus (HCV) RNA is essential for the everyday management of chronic hepatitis C therapy. Real-time polymerase chain reaction (PCR) techniques are potentially more sensitive than classical PCR techniques, are not prone to carryover contamination, and have a consistently wider dynamic range of quantification. Thus, they are rapidly replacing other technologies for the routine quantification of HCV RNA. We extensively evaluated the intrinsic characteristics and clinical performance of Cobas Ampliprep/Cobas TaqMan (CAP/CTM), the most widely used real-time PCR assay for HCV RNA quantification. This study shows that CAP/CTM is sensitive, specific, precise, and reproducible and has a broad dynamic range of quantification well suited to HCV RNA monitoring in clinical practice. However, we identified 2 technical issues that will have an impact in clinical practice. First, the CAP/CTM assay overestimates HCV RNA levels in undiluted patient samples by approximately 0.6 log(10) international units per milliliter on average, and this overestimation increases with the viral load. Second, the CAP/CTM assay substantially underestimates HCV RNA levels in approximately 15% of genotype 2 samples and 30% of genotype 4 samples, probably because of mismatches with the target sequences due to the primer and/or probe design. CONCLUSION: As the CAP/CTM platform is widely available, easy to use, and suited to high-throughput screening for viral genomes, the manufacturer should improve the HCV RNA kit to resolve these 2 important technical issues that may affect everyday management of hepatitis C therapy.

Chevaliez S, Brillet R, Lázaro E, Hézode C, Pawlotsky JM. · Department of Virology, Hôpital Henri Mondor, Université Paris 12, Créteil, France. · J Virol. · Pubmed #17494069 links to  free full text

Abstract: The addition of ribavirin to alpha interferon therapy significantly increases response rates for patients with chronic hepatitis C virus (HCV) infection, but ribavirin's antiviral mechanisms are unknown. Ribavirin has been suggested to have mutagenic potential in vitro that would lead to "error catastrophe," i.e., the generation of nonviable viral quasispecies due to the increment in the number of mutant genomes, which prevents the transmission of meaningful genetic information. We used extensive sequence-based analysis of two independent genomic regions in order to test in vivo the hypothesis that ribavirin administration accelerates the accumulation of mutations in the viral genome and that this acceleration occurs only when HCV replication is profoundly inhibited by coadministered alpha interferon. The rate of variation of the consensus sequence, the frequency of mutation, the error generation rate, and the between-sample genetic distance were measured for patients receiving ribavirin monotherapy, a combination of alpha interferon three times per week plus ribavirin, or a combination of alpha interferon daily plus ribavirin. Ribavirin monotherapy did not increase the rate of variation of the consensus sequence, the mutation frequency, the error generation rate, or the between-sample genetic distance. The accumulation of nucleotide substitutions did not accelerate, relative to the pretreatment period, during combination therapy with ribavirin and alpha interferon, even when viral replication was profoundly inhibited by alpha interferon. This study strongly undermines the hypothesis whereby ribavirin acts as an HCV mutagen in vivo.

Bouchardeau F, Cantaloube JF, Chevaliez S, Portal C, Razer A, Lefrère JJ, Pawlotsky JM, De Micco P, Laperche S. · Institut National de la Transfusion Sanguine, 6 Rue Alexandre-Cabanel, 75015 Paris, France. · J Clin Microbiol. · Pubmed #17251399 links to  free full text

Abstract: Hepatitis C virus (HCV) isolates have been classified into six main genotypes. Genotyping methods, and especially the widely used line probe assay (LiPA), are frequently based on the 5'-untranslated region (5'UTR). However, this region is not appropriate for discriminating HCV strains at the subtype level and for distinguishing many genotype 6 samples from genotype 1. We investigated the capacity of a novel LiPA (Versant HCV Genotype 2.0 assay) based on the simultaneous detection of 5'UTR and Core regions for genotypes 1 and 6 to provide correct HCV genotypes (characterized with a phylogenetic analysis) in a set of HCV strains mainly encountered in Western countries. The improvement was assessed by comparing the results to those obtained with the previous version of the assay. Of the 135 tested samples, 64.7% were concordant for genotype group and subtype with sequencing reference results using the Versant HCV Genotype 2.0 assay versus 37.5% with the previous version. The yield was mainly related to a better characterization of genotype 1, since the accuracy, tested in 62 genotype 1 samples, increased from 45.2% with the first version to 96.8% with the new one. However, this new version necessitates a specific PCR and could no longer be used after 5'UTR PCR used for current HCV infection diagnosis. Moreover, the information provided by 5'UTR hybridization is not reliable for correctly identifying the diversity within genotypes 2 and 4. Thus, the Versant HCV Genotype 2.0 assay remains a useful tool for clinical practice when only the discrimination between major HCV genotypes is necessary.

Bronowicki JP, Ouzan D, Asselah T, Desmorat H, Zarski JP, Foucher J, Bourlière M, Renou C, Tran A, Melin P, Hézode C, Chevalier M, Bouvier-Alias M, Chevaliez S, Montestruc F, Lonjon-Domanec I, Pawlotsky JM. · Department of Hepatology and Gastroenterology, INSERM U724, CHU de Nancy, Vandoeuvre-les-Nancy, France. · Gastroenterology. · Pubmed #17030174 No free full text.

Abstract: BACKGROUND & AIMS: Pegylated interferon alfa-ribavirin combination is the standard treatment for chronic hepatitis C, but the mechanisms by which ribavirin enhances the rate of sustained hepatitis C virus (HCV) eradication remain unknown. We aimed to investigate the role of ribavirin in HCV clearance during therapy and to evaluate the consequences of ribavirin discontinuation in patients infected with genotype 1 hepatitis C who cleared HCV RNA at week 24. METHODS: A total of 516 patients were treated with pegylated interferon alfa-2a, 180 microg/wk, plus ribavirin, 800 mg/day. Seventy percent were RNA negative at week 24. They were randomized to continue with the combination or receive pegylated interferon alone. RESULTS: Responders at week 24 who stopped ribavirin had a significantly higher rate of breakthroughs during, and relapses after, therapy (sustained virologic response, 52.8% vs 68.2%; P = .004), but their side-effect profile and quality of life tended to improve. Multiple logistic regression analysis in the pegylated interferon alfa monotherapy group allowed identification of responders at week 24 who could stop ribavirin without losing their chance of a sustained virologic response, based on baseline viral load and age. Forty-eight weeks of ribavirin may not be needed when HCV RNA is undetectable at week 2. CONCLUSIONS: We made 3 conclusions from this study. First, ribavirin primarily acts by sustaining the virologic response to pegylated interferon alfa; second, ribavirin must be administered for the full treatment duration in most genotype 1-infected patients who respond; third, baseline parameters may help identify patients who could discontinue ribavirin or reduce the dose without losing their chance of success.

Chevaliez S, Pawlotsky JM. · Department of Virology, INSERM U635, Henri Mondor Hospital, University of Paris XII, Créteil, France. · Int J Med Sci. · Pubmed #16614740 links to  free full text

Abstract: 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.

Chevaliez S, Bouvier-Alias M, Castéra L, Pawlotsky JM. · No affiliation provided · Hepatology. · Pubmed #19330876 No free full text.

This publication has no abstract.