F Zoulim

..Our results showed that ADV administration for 48-72 weeks effectively suppresses HBV replication without the emergence of resistant viral mutants...

..Further studies in larger cohort of patients are warranted to determine if occult HBV co-infection may be involved in HCV resistance to combination therapy...

..This review will discuss HBV and HCV morphogenesis, with a particular focus on the role of N-glycosylation for viral protein folding and assembly, and will present the antiviral properties of glucosidase inhibitors...

..Also, human intervention in the form of mass vaccination and antiviral treatment will reduce the burden of HBV-related liver disease but may also be accelerating evolution of the virus...

..Because of the variability of the HBV genome, such long-term treatments are associated with the emergence of resistant viral strains, which may compromise the initial clinical benefit of the treatment...

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..Clinical studies are ongoing to determine the best strategy to prevent or delay antiviral drug resistance and of its impact on liver disease...

..A better knowledge of the pathobiology of HCV and its clinical consequences will be important for developing better treatment strategies to cure HCV infection and extrahepatic manifestations...

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..Our aim was to evaluate the anti-HBV activity of a novel L-nucleoside analog, 2',3'-dideoxy-2',3'-didehydro-beta-L-5-fluorocytidine (beta-L-Fd4C), in study models of HBV infection...

..The mechanism of HBV resistance to nucleoside analogs are described as well as the concept for multiple drug therapy and combination with immunostimulatory approaches...

..Discovery of new antiviral drugs and design of new treatment strategies are, therefore, needed to manage this disease, which is still the main cause of cirrhosis and hepatocellular carcinoma worldwide...

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..The availability of entecavir as a new treatment option is providing clinicians more choice to keep both viral replication and liver disease under control. This provides new hope for improved treatment concepts for chronic HBV infection...

..However, the development of new antiviral agents is rapidly improving the offing of therapy of chronic hepatitis B. These new therapeutic advances are reviewed in this manuscript...

..These results indicate that beta-L-Fd4C exhibits a more potent antiviral effect than lamivudine in the WHV model but was not able to eradicate CCC DNA and infected cells from the liver at the dosage and with the protocol used...

..However, no extra benefit of adding IFN-gamma gene transduction to the L-FMAU/FTC combination could be detected...

..These findings demonstrate the potential of SATE pronucleotides of ACV as anti-HBV agents...

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..Furthermore, our results provide the rationale for further clinical evaluation of FLG in the treatment of drug-resistant virus infection and in the setting of combination therapy to prevent or delay drug resistance...

..We selected sera from 50 patients with chronic hepatitis of unknown aetiology who were enrolled in this follow-up study whose aim is to gain insight into the possible role of viruses and to define potential clinical outcomes...

..To study the biology of these mutants, we analyzed their replication capacity in the duck hepatitis B virus (DHBV) infection...

..This prospective cohort study identified lamivudine-resistant mutations emerging in 22% of subjects, yearly, which were apparently not associated with clinical aggravation over the study period...

..Such an occult HBV co-infection is associated with more severe liver disease, higher HCV viral load and decreased response to antiviral therapy irrespective of HCV genotypes...

..Altogether these results suggest that ribavirin may not exhibit a direct antiviral effect, but may trigger a favourable response to interferon by modulating the immune response against HCV...

..However, no viral clearance from the liver was observed, suggesting that the enhanced antiviral effect of this combination was not sufficient for cccDNA suppression and HBV eradication from infected cells...

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..Appropriate management of chronic hepatitis B must rely not only on the standard serologic markers but also on tests that quantify viral load and on the study of viral genome variability according to clinical situation...

..Taken together, these results show that hepatocyte proliferation may positively regulate the initial amplification of CCC DNA of avian hepadnaviruses, and may explain why mitosis is not necessarily associated with loss of CCC DNA...

..In HIV/HBV-coinfected patients, most of them with normal ALT under antiretroviral treatment including HBV active drugs, TE was proficient in discriminating moderate to severe fibrosis from minimal liver disease...

..However, other nucleos(t)ide analogs in development showed an antiviral activity against this multiresistant strain in vitro. This provides a rationale for the clinical evaluation of de novo combination therapies...

..Most drug-resistant mutants, including multidrug-resistant strains, remained sensitive to tenofovir and PMEO-DAPym. Therefore, the latter molecule deserves further evaluation for the treatment of HBV infection...

..After 1 year of therapy, a median 3.5-4.0 log10 decrease in viral load is observed. Our aim was to characterize the different profiles of response to ADV in relation to the in vitro susceptibility of viral strains to ADV...

..Taken together, our results demonstrate that adefovir is a potent inhibitor of DHBV replication that inhibits CCC DNA amplification but does not effectively prevent the formation of CCC DNA from incoming viral genomes...

..In conclusion, the unique mechanism of action of these new inhibitors warrants further evaluation in experimental models to determine their capacity to delay or prevent the selection of drug resistant mutants...

..There are evidences that occult HBV is a risk factor for the development of HCC and that the potential mechanisms whereby overt HBV might induce tumour formation are mostly maintained...

..Therefore, sexual HCV reinfection can occur in homosexual men having unprotected sex and "serosorting" should be considered a risk factor for the sexual transmission of HCV...

..Three of the four tested compounds were able to selectively inhibit DHBV replication by acting at an early step of the hepadnavirus infection but were associated with significant toxicity...

..In conclusion, HBV infection in differentiated HepaRG cells is characterized by long-term persistence without a key feature of hepadnaviruses, the so-called 'CCC DNA amplification' described in the duck hepatitis B model...

..It can also be used to probe HBV cccDNA, the crucial intermediate in viral persistence and the archive of resistance mutations...

..These advances provide new hope in the management of chronic hepatitis C, including patients with hereditary bleeding disorders...

..The search for new viral targets is therefore mandatory to design combination strategies to prevent the emergence of resistant mutants and eventually clear viral infection...

..However, de novo combination is recommended in patients whose liver functions cannot tolerate treatment failure, and in patients with a high risk of developing viral resistance because of a complex viral quasi-species prior to therapy...

..During natural infection with hepatitis C virus (HCV), the interactions between the virus and DC may contribute to viral persistence, a general feature of HCV infection...

..Combination of these new anti-HBV agents with DNA based immunization may prove useful to eradicate viral infection...

..In conclusion, an improved cell-culture system was established for the transduction of replication-competent HBV genomes. This will be useful for future studies of the fitness of HBV mutants...

..009). No difference in patient survival was observed in the two groups. In conclusion, this study shows that HCV eradication has a positive impact on graft survival...

..Our aim was to establish the proof of concept of the antiviral benefit of combining a nucleoside analogue with CpG-induced cytokines on HBV replication in vitro...

..Clinical experience shows that an optimal management of antiviral therapy allows the control of viral replication in the majority of patients in whom liver disease progression is halted...

..This effect was sustained since it was observed 12 weeks after the end of therapy. CONCLUSIONS: Our results suggest that combination of adefovir with DNA-vaccine may be able to induce a sustained antiviral effect in vivo...

..In this study, we characterized the main variants harboring the rtA181T/V mutation isolated from 10 consecutive patients who developed lamivudine and/or adefovir resistance...

..This study examined the long term biochemical, virological, and histological outcome in transplanted patients with recurrent chronic hepatitis who had a sustained virological response to antiviral therapy...

..Long-term ADV therapy significantly decreased cccDNA levels by a primarily noncytolytic mechanism...

..The recently revised benefit-to-risk ratio remains highly favorable for vaccination. Current data indicates that the policy of mass vaccination of the population should be pursued...

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..These results also highlight the importance of antiviral drug potency and an effective DNA immunization protocol for the design of therapeutic vaccines against chronic hepatitis B...

..Complex mutants may be selected under sequential anti-VHB pressures. We analyzed the genotypic and phenotypic evolution of the viral quasi-species of a patient who developed resistance to entecavir following lamivudine breakthrough...

..The different in vitro models for the study of HBV resistance include enzymatic and cell-based assays. Their relevance for the analysis of viral fitness, drug susceptibility, and cross-resistance is also reviewed...

..These assays are described and their potential use in the clinical setting is discussed...

..Therefore, DNA-based vaccine appears as a promising new approach for prophylaxis and therapy of hepatitis B...

..The humoral response was similar between groups. In conclusion, viral breakthrough does not seem to be due to selection of resistant strains with signature mutations...

..This report suggests that in patients who previously failed lamivudine therapy, proactive antiviral treatment may lead to a beneficial virological and clinical effect...

..In conclusion, the cryptic nature of this double HBV infection is characterized by the predominance of the replication-deficient genotype D virus over the replication-competent genotype A virus...

..The development of true combination therapy is highly desirable to fulfil the objective of long-term viral suppression, clearance of viral cccDNA and infected cells and ultimately cure of the disease...

..For patients with severe disease, liver transplantation is the treatment of choice. The aim of this study was to report the long-term outcome of patients who underwent liver transplantation for Wilson's disease...

..Besides mass HBV vaccination programmes, people sharing a house with patients infected with HBV should be vaccinated to prevent viral transmission...

..To fulfill this objective, prospective studies are still warranted for the the spread of sensitive and standardized techniques standardization of the quantification assays and to define cut off values with clinical predictive values...

..A mass influenza A/H1N1 vaccination campaign took place in France during the 2009 winter. Overall, 7.9% of the general population was vaccinated. However, vaccine coverage data are missing for at-risk groups...

..These improved strategies should enhance treatment success enough to obtain clinical stabilization, to delay or prevent the need for transplantation, and to reduce the risk of hepatitis B virus recurrence on the graft.AASLD...

..This retrospective cohort study evaluated the safety and efficacy of ADV in this specific patient population...

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..The future perspectives are to design strategies to hasten the HBsAg clearance, which should become a new treatment endpoint, to prevent drug resistance and to decrease the incidence of complications of chronic hepatitis B...

..These results could explain the synergistic effect of ribavirin and IFN in combined therapy in chronic carriers of HCV. This effect must be confirmed with subgenomic replicons of HCV...

..For each patient, its indication has to be weighed against the risk of developing viral resistance but also against the risk of natural history of the disease...

..Cynomolgus macaques are readily available, are immunologically closely related to humans, and may therefore represent a promising model for the development of new immunotherapeutic strategies...

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..For patients coinfected with HIV, hepatitis B treatment options that aim to reduce the risk of HBV mutations from emerging must be seriously considered, not only from clinical but also public health perspectives...

..The development of these different treatment options has made possible very significant improvements in the management of patients with chronic hepatitis B, by preventing aggravation of liver disease in most of them...

..Most of the isolates fall into the second category. Mutations can therefore contribute to HBsAg seronegativity in occult HBV infections, but in most cases the explanation is probably the low level of viral replication...

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..Duck hepatitis B virus (DHBV) replication is up-regulated by cell cycle during the early infection of primary duck but the effect of cell cycle on DHBV replication in chronically infected hepatocyte is not known...

..Although many of the clinical studies are initially undertaken in non-haemophilia individuals, consideration needs to be given as to the possible benefits of including those with haemophilia in the clinical assessment...

..Our goal was to identify their needs thanks to the analysis of questionnaires in order to improve their care...

..This assay should allow a better monitoring of patients undergoing antiviral therapy, as well as the screening of novel drugs on emerging resistant strains...

..These properties suggest the potential usefulness of DNJ derivatives in combating HCV infection...

..1 could be a potent "next generation" IFN for the treatment of HCV infection, especially in nonresponders or relapsing patients infected with HCV genotype 1 who currently represent a clinical unmet need...

..While great progress has been made in treating hepatitis B, many important issues require further study...

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..Furthermore, current antiviral therapy is not very effective in these populations. Thus, it is especially important to protect patients at risk for HCV infection, using universal precautionary procedures...