Interferon‐α therapy does not modulate hepatic expression of classical type I interferon inducible genes

Abstract

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. Treatment with interferon-alpha(2) (IFN-alpha(2)) can induce viral clearance and marked biochemical and histological improvement. IFN-alpha(2) treatment has been shown to stimulate the expression of type I IFN regulated genes in peripheral blood mononuclear cells (PBMCs) of hepatitis C patients; however, whether it affects hepatic expression remains unknown. This study thus aimed at comparing hepatic gene expression with particular emphasis on type I IFN inducible genes in patients with chronic hepatitis C before and during an IFN-alpha(2) monotherapy. Responsiveness to IFN-alpha(2) therapy was monitored by determining serum and hepatic viral load. Differential gene expression analysis was performed by two different techniques, namely suppression subtractive hybridization (SSH) and differential display (DD). Expression of two prototype type I IFN regulated genes was quantified in further PBMC and liver samples. Among different genes found to be up-regulated during an effective, that is, virus clearing, IFN-alpha treatment, only a single one was identified which can be accounted to type I IFN responsive genes. Parallel quantitative real time PCR analyses demonstrated significant induction of the type I IFN regulated genes MxA and PKR in PBMC, but not in the liver. Taken together, while IFN-alpha treatment leads to the induction of type I IFN regulated genes in PBMC, such an induction appears not to occur in the liver of hepatitis C patients. The mechanism by which IFN-alpha treatment causes viral clearance might be independent of hepatic activation of type I IFN regulated genes.