Interferon therapy of hepatitis C: molecular insights into success and failure

20 years have passed since the discovery of the hepatitis C virus (HCV), and yet therapeutic options remain limited. Current standard treatment of chronic hepatitis C (CHC) consists of pegylated interferon alpha (pegIFN) and ribavirin, and leads to a sustained virological response in approximately half of treated patients. Understanding non-responsiveness to pegIFN, by analysing the molecular mechanisms underlying treatment failure, is important for future therapeutic improvements. In the following review the current status of knowledge on the crosstalk between HCV and IFNs, as well as on the molecular events occurring in liver tissue of HCV-infected patients in response to pegIFN, is discussed. Furthermore, the review focuses on the prospect of developing a prognostic test that might direct treatment to those patients who will benefit from it. The outlook on novel therapeutics, including small molecule inhibitors of HCV proteins and immune modulators, is broadened by a glance at the exciting field of micro-RNAs that are likely to be implicated in viral replication and pathogenesis of CHC, thus representing a new therapeutic target.