J M Pawlotsky

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

..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...

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

..Whether response-guided therapy will still be useful in the era of all-oral, interferon-free regimens remains uncertain...

..Further results are awaited that will allow the establishment of an ideal first-line all-oral, interferon-free treatment regimen for patients with chronic HCV infection...

..HRQL improves after successful treatment. This trial explores the course of and factors associated with HRQL in patients given individualized or standard treatment based on early treatment response (Ditto-study)...

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..These new drugs all potentially select resistant viral variants both in vitro and in vivo, and resistance is therefore likely to become an important issue in clinical practice...

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..The future of hepatology as a specialty will depend on the success of this initiative...

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

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

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..HCV quasispecies variability also has therapeutic implications, as the continuous generation and selection of fitter or truly resistant variants can allow the virus to escape control by antiviral drugs...

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

..GBV-C is sensitive to 3 mega units of interferon alfa administered three times per week in two-thirds of the patients, but relapse is constant with this dosage after treatment withdrawal...

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..The aim of the present study was to evaluate in patients with CHC and paired liver biopsies the relationship between the evolution of steatosis and that of fibrosis between the two biopsies...

..Transient elastography measures liver stiffness, which correlates with the hepatic fibrosis stage and has excellent accuracy for the diagnosis of cirrhosis in patients with chronic hepatitis C...

..0 is not influenced by the HCV genotype. The relationship between values obtained with assays 1.0 and 2.0 on clinical specimens is not linear, indicating that HCV RNA titers cannot reliably be calculated from the results of version 1.0...

..These findings suggest that steatosis is a cytopathic lesion induced by HCV genotype 3, whereas HCV genotype 1 is not steatogenic per se or at the usual in vivo expression levels...

..This study emphasizes the need for more sensitive, university standardised quantitative HBV DNA assays and for the definition of clinically relevant cutoffs with these assays...

..Given their respective performance, these three assays should be used in complementary fashion in the management of HBV-infected patients...

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

..Total lifetime tobacco consumption was recorded as the number of cigarette packs smoked per year (packs-years). Liver biopsy specimens were graded for histological activity and fibrosis according to the METAVIR scoring system...

..To evaluate the effects of minimal to moderate alcohol consumption on the severity of histological lesions in patients with chronic hepatitis C...

..These changes are associated with profound alterations of the natural outcome of HCV-related liver disease, raising the hypothesis of a causal relationship...

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..To clarify this point, we studied serum HCV RNA levels in patients with HCV liver disease at various stages, using a second-generation branched DNA (bDNA) assay...

..To investigate this hypothesis, we studied the relationship between steatosis evolution and HCV clearance after antiviral treatment in patients with chronic hepatitis C and paired liver biopsies...

..A phylogenetic analysis showed a high percentage of nucleotide homology between the two patients' strains...

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

..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...

..Subtyping of 1a and 1b is still not possible with the existing peptides, but discriminating between subtypes may not be necessary for routine use...

..MC may contain viral RNA, and tissues showing vasculitis may contain intracellular HCV. Local HCV replication remains to be evidenced...

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..e. the endpoint of therapy...

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

..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...

..The modification of the HCV genotype pattern in France in the next 10 years may require new therapeutic strategies, and further survey studies...

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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...

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

..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...

..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...

..The nonstructural (NS) 5A protein of hepatitis C virus (HCV) has been suggested to contain an interferon (IFN) sensitivity-determining region (ISDR)...

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

..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...

..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...

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

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

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

..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...

..Recent reports suggest that the virological response at week 4 could be used to tailor treatment duration, whatever the HCV genotype...

..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...

..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...

..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...

..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...

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

..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...

..To date, this virus has not been associated with acute or chronic hepatitis and as such hepatitis G virus is a misnomer. This orphelin virus is thus still looking for the right name and perhaps an induced pathology...

..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...

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

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..Serological results should be interpreted with care when serum is macroscopically abnormal, and cadaveric donors should not be sampled more than 12 hr after death...

..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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..CONCLUSION: These cases suggest that infliximab therapy may be safe in some quiescent or controlled chronic HBV or HCV infection...

..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...

..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...

..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...

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..Our findings also suggest that individual treatment optimization will require sensitive methods capable of detecting the emergence of viral resistance before the relevant variants acquire optimal replicative capacities...

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..In conclusion, these proposals provide the framework by which the HCV databases store and provide access to data on HCV, which will internationally coordinate the assignment of new genotypes and subtypes in the future...

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

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

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

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..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...

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

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

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