It has become the most common cause of chronic liver disease, and yet there continues to be a lack of effective therapeutic options. This article reviews current concepts underlying the pathophysiological basis of nonalcoholic steatohepatitis from development of insulin resistance to the establishment of fibrosis. Then using a physiology-based approach, specific targeted therapeutics are reviewed along with their drawbacks. The evidence behind current therapies is based predominantly on small trials and, thus, no recommendations can be made until larger randomized trials are

conducted. “
“Hepatitis B virus (HBV) resistance to nucleoside/nucleotide analogs is frequent. Ultra-deep pyrosequencing (UDPS) is a powerful new tool that can detect minor viral variants and characterize complex quasispecies mixtures. We used UDPS SCH 900776 molecular weight to analyze the dynamics of adefovir-resistant HBV variants in patients with chronic HBV infection in whom adefovir resistance occurred during treatment. Amino acid substitutions known to confer resistance to adefovir were detected at baseline in most patients. The dynamics of adefovir-resistant variants were complex and differed among patients as a result of evolving differences in variant fitness.

UDPS analysis revealed successive selleck chemical waves of selection of HBV populations with single and multiple amino acid substitutions. Adefovir-resistant variants were partially inhibited by lamivudine, but remained fit in its presence. Conclusion: Substitutions conferring HBV resistance to nucleoside/nucleotide analogs exist before treatment, and that the dynamics of adefovir-resistant populations are much more complex and heterogeneous MCE than previously thought and involve thus far unknown amino acid substitutions. The UDPS-based approach described here is likely to have important implications for the assessment

of antiviral drug resistance in research and clinical practice. (Hepatology 2013;53:890–901) Approximately 240 million individuals worldwide are chronically infected with hepatitis B virus (HBV).[1] Chronic HBV infection is the leading cause of chronic liver disease and accounts for nearly 1 million deaths every year.[2-4] Chronic hepatitis B (CHB) can be treated with either pegylated interferon alpha or nucleoside/nucleotide analogs. The latter drugs act by directly inhibiting the enzymatic function of HBV reverse transcriptase, the enzyme responsible for viral replication. Five such drugs have been approved for HBV therapy, namely, three nucleoside analogs (lamivudine, telbivudine, and entecavir) and two nucleotide analogs administered as prodrugs (adefovir dipivoxil and tenofovir disoproxil fumarate). The vast majority of HBV-infected patients have an indication for therapy with nucleoside/nucleotide analogs.