Old and emerging therapies in chronic hepatitis C: an update.

The main goal of therapy in hepatitis C virus (HCV) infection is to achieve a sustained virological response currently defined as undetectable HCV-RNA in peripheral blood determined with the most sensitive polymerase chain reaction technique 24 weeks after the end of treatment. This goal is practically equivalent with eradication of HCV infection and cure of the underlying HCV-induced liver disease. The current standard in hepatitis C treatment consists in combination regimens of pegylated interferon-alpha (Peg-INF-alpha) with Ribavirin (RBV). Such treatment schemes are quite successful in patients with HCV genotypes 2 and 3 infections achieving HCV eradication rates of 75-90%. However, they are much less effective in patients with genotypes 1 and 4 infections with eradication rates ranging between 45% and 52%. Moreover, they have several, and sometimes severe, adverse effects and contraindications, further limiting their efficacy and applicability in an appreciable number of patients with chronic HCV-induced liver disease. Therefore, the need for improvement of existing therapies and for development of new effective, safe and tolerable drugs is a matter of great clinical relevance and importance. In this article, recent improvements in the current standard of therapy with IFN-alpha and RBV in various subsets of patients with chronic hepatitis C and in the clinical development of new emerging drugs, particularly small molecules, will be reviewed and commented. The article is divided in two main parts: (i) improvements in the standard combination therapies and schemes of approved Peg-INF-alpha with RBV and expectations from new interferons, interferon inducers and alternatives to RBV; (ii) new drugs for HCV in clinical development focusing mostly on specific inhibitors of HCV and less so on other drugs including immune therapies.