05). In multivariate analysis, independent predictors of HCV/AIH were ANA positivity, female sex, higher HCV RNA, ALT and globulin fraction. 11 liver

biopsies from HCV/AIH cases were compared to matched controls. There was no difference in the presence of plasma cells in portal and lobular areas, rosette formation, emperipolesis, bridging necrosis and perivenular necrosis. However, HCV/AIH cases had higher periportal HAI inflammatory scores (p=.008) despite similar ALT levels. Conclusion: ANA positivity is common in patients with HCV (38%). Among patients with chronic HCV infection, ANA positivity, female sex, higher baseline HCV RNA, ALT, globulin fraction and greater periportal inflammation are suggestive of co-existent HCV/AIH. Disclosures: The following people have nothing to disclose: Yun Ju Kim, Anthony Loria, Xiongce Zhao, David E. Kleiner, Marc G. Ghany “
“RNA interference (RNAi) is being evaluated STI571 research buy as an alternative therapeutic strategy for hepatitis C virus (HCV) infection. The use of CH5424802 nmr viral vectors encoding short hairpin RNAs (shRNAs) has been the most common strategy employed to provide sustained expression of RNAi effectors.

However, overexpression and incomplete processing of shRNAs has led to saturation of the endogenous miRNA pathway, resulting in toxicity. The use of endogenous microRNAs (miRNAs) as scaffolds for short interfering (siRNAs) may avoid these problems, and miRNA clusters can be engineered to express multiple RNAi effectors, a feature that may prevent RNAi-resistant HCV mutant generation. We exploited the endogenous miRNA-17-92 cluster to generate medchemexpress a polycistronic primary miRNA that is processed into five mature miRNAs that target different regions of the HCV genome. All five anti-HCV miRNAs were active, achieving

up to 97% inhibition of Renilla luciferase (RLuc) HCV reporter plasmids. Self-complementary recombinant adeno-associated virus (scAAV) vectors were chosen for therapeutic delivery of the miRNA cluster. Expression of the miRNAs from scAAV inhibited the replication of cell culture–propagated HCV (HCVcc) by 98%, and resulted in up to 93% gene silencing of RLuc-HCV reporter plasmids in mouse liver. No hepatocellular toxicity was observed at scAAV doses as high as 5 × 1011 vector genomes per mouse, a dose that is approximately five-fold higher than doses of scAAV-shRNA vectors that others have shown previously to be toxic in mouse liver. Conclusion: We have demonstrated that exogenous anti-HCV miRNAs induce gene silencing, and when expressed from scAAV vectors inhibit the replication of HCVcc without inducing toxicity. The combination of an AAV vector delivery system and exploitation of the endogenous RNAi pathway is a potentially viable alternative to current HCV treatment regimens. (HEPATOLOGY 2010.