| Hepatitis C virus (HCV) infection and alcoholic liver disease synergistically promote the progression of advanced liver disease and non-response to interferon (IFN)-based antiviral therapy. The purpose of this study is to explore how ethanol (EtOH) establishes a favorable environment for HCV replication by deregulating antiviral innate immunity in the hepatocyte.;Results show that not all of the known anti-HCV interferon (IFN) stimulated genes (ISGs), which are the effectors of intracellular innate immunity, are inducible in the hepatocyte. In addition, the mRNA induction of selected anti-HCV hepatocyte-inducible ISGs by IFN is impaired in the presence of EtOH in vitro, though mRNA induction by IFN and impairment by EtOH in vivo can vary from in vitro results. Furthermore, the induction of a potent ISG IRF1 is heterogeneous among hepatocytes in EtOH-fed mice.;In conclusion, EtOH attenuates the ISG response, and this defect in antiviral immunity may be partially attributable to suppressed response to therapeutic IFN in EtOH consuming patients, therefore increasing susceptibility to advanced liver disease. |
