Jean Michel Pawlotsky

..The HCV genotype and on-treatment viral kinetics can be used to tailor treatment dosages and duration...

..This article reviews the kinetics of HCV markers during acute and chronic HCV infection, together with current assays and their practical use in the management of HCV-infected patients...

..This study strongly undermines the hypothesis whereby ribavirin acts as an HCV mutagen in vivo...

..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...

..Our aim was to assess the antiviral action of ribavirin on hepatitis C virus (HCV) as a function of ribavirin pharmacokinetics and to evaluate the influence of this antiviral effect on IFN-alpha efficacy...

..We review these new virologic methods and their clinical and research applications to HBV and HCV infections...

..The goal of this study was to identify the appropriate molecular tool(s) for accurate HCV genotype 1 subtype determination...

..The aim of this study was to test the principal isomers contained in silymarin preparations for their ability to inhibit HCV enzymatic functions and replication in different models...

..These approaches will be particularly useful in studying the mechanisms of HCV treatment failure with new HCV inhibitors currently under development...

..The influence of genetic determinants in this context remains unknown...

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..During chronic HCV infection, activation of fibrogenesis appears to be principally related to local inflammation. However, the direct role of hepatic HCV protein expression in fibrogenesis remains unknown...

..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...

..Overall, the CAP/CTM assay, version 2.0, is well suited to monitoring clinical HBV DNA levels according to current clinical practice guidelines...

..This article reviews current molecular biology-based techniques and assays, and their practical use in the management of hepatitis B and C virus infection...

..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...

..Further studies are needed to understand better the implications of HCV quasispecies diversity in the pathophysiology of HCV infection...

..Telaprevir is a specific inhibitor of the HCV serine protease and could be of value in HCV treatment...

..New treatments and vaccines might make it possible to eradicate HCV in the future...

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..Virological tools are used in clinical practice to diagnose acute and chronic HCV infection, to decide who should be treated, to select the optimal therapy and to monitor treatment responses in order to tailor treatment duration...

..In conclusion, daily cannabis smoking is significantly associated with fibrosis progression during CHC. Patients with ongoing CHC should be advised to refrain from regular cannabis use...

..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...

..These improvements, and the development of new antiviral drugs (see the article by Drs. DeFrancesco and Rice elsewhere in this issue), should help to optimize the treatment of HCV infection...

..IFN resistance could also play a role in the virological response to IFN therapy through similar or different mechanisms. The involved mechanisms however remain unclear...

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..The role of HCV proteins in hepatocarcinogenesis is unknown. Further progress in our understanding of HCV infection and pathogenesis awaits the advent of new model systems and technologies...

..Then, we will provide an overview of how these models have contributed to the deciphering of the molecular mechanisms underlying dysregulated lipid metabolism and hepatocellular carcinoma during HCV infection...

..In conclusion, CAP/CTM HCV v2.0 accurately quantifies HCV RNA in genotype 4 clinical specimens, regardless of the subtype, and can be confidently used in clinical trials and clinical practice with this genotype...

..Finally, insights into new hepatitis C drug developments are given...

..Whether these adefovir resistance-associated substitutions may confer cross-resistance to tenofovir in vivo will need to be determined...

..This article discusses current knowledge of the mechanisms of action of IFN-alpha and ribavirin, the virological characteristics of chronic hepatitis C treatment success and failure, and possible underlying mechanisms...

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..Thus, virological assays are indispensable in the diagnosis and management of individuals infected with the HCV...

..This article discusses HBV virologic markers and tests, and their optimal use both for planning and reporting clinical trials and in clinical practice...

..Taken together, these results demonstrate a new mechanism by which HCV modulates its cellular environment, thereby enhancing viral replication...

..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...

..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...

..CONCLUSION: This suggests that other viral proteins and/or host factors are involved in the development of hepatocellular steatosis in patients infected by HCV genotype 3a...

..Cryoglobulinemia did not seem to be associated with more severe graft damage. Cryoglobulinemia-associated morbidity must be taken into account in the management of post-transplant HCV infection...

..e. the endpoint of therapy...

..Thus, there is a need to standardize nomenclature relating to hepatitis B antiviral resistance, and to define genotypic, phenotypic, and clinical resistance to NA therapy...

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..The drugs, currently in phase 1 and 2, which will demonstrate their efficacy and safety, should not be available before several years...

..Analysis of hepatitis C virus (HCV) RNA kinetics in compartments other than plasma may help in understanding HCV replication and identifying clinically significant patterns of treatment response...

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..Despite the substantial advances in treatment made to date, new agents with novel viral targets will be needed for patients who ultimately may fail second- or third-line therapy...

..Prospective studies are required to determine the potential utility of the marker panel in guiding treatment decisions and following disease progression...

..Potential strategies to prevent the emergence of resistance and how to manage drug-resistant HBV once it emerges are discussed...

..No HIV-seronegative, HIV RNA-positive donor was identified. Our data suggest that routine nucleic acid testing of organ and tissue donors might increase viral safety in transplantation...

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..This feature of quasispecies-distributed viruses could play an important role in various aspects of the viral life cycle and related disease...

..These results show that IFN-alpha acts primarily through its nonspecific antiviral effects and suggest that primary cultures of human hepatocytes may provide a good model to study intrinsic HCV resistance to IFN-alpha...

..These results argue against an in vivo interaction between HCV and EBV in patients with AIDS, and against a role of HCV infection in the occurrence of B-cell non-Hodgkin's lymphoma in these patients...

..In contrast, the overall quasispecies distribution of HCV genomes (including IRES sequences) might participate in regulation of hepatic and extrahepatic HCV replication...

..Nevertheless, the total HCV core Ag assay cannot be used as a marker of viral replication for HCV RNA values below 20,000 IU/mL, limiting its use in the monitoring of late events during and after antiviral treatment...

..Furthermore, no obvious nucleotide changes in the surrounding IRES region that might possibly affect oligonucleotide binding were detected...

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..Drug combinations will be tailored to the individual patient, based on baseline parameters and viral kinetics during therapy...

..Thus, pretreatment IP-10 analysis may prove helpful in decision-making regarding pharmaceutical intervention...

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..Furthermore, the clinical implications of HBV genotyping and the determination of precore/core mutants need to be clearly stated to justify the standardization of these methods...

..CONCLUSION: Baseline IP-10 levels are predictive of the response to HCV treatment...

..Regional transmission occurred in the recent past, leading to an embryonic genetic diversification of HCV-3a among local injecting drug user population...

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..The issue of cccDNA clearance, however, remains in hepatitis B treatment, whereas HCV infection is curable...

..The aim of this study was to increase virologic response rates by individualized treatment according to the early virologic response...

..By preserving a balance between these functions, HVR1 may be essential for the viral persistence of HCV...

..These results provide new insights into the mechanisms of viral persistence and immune control of viremia...

..These results emphasize the need for commercial HCV RNA quantification assays with a broader range of linear quantification, such as real-time PCR-based assays...

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