Small molecule and novel treatments for chronic hepatitis C virus infection.

The development of molecular-based therapies for the treatment of chronic hepatitis C virus (HCV) infection is an area of intense clinical research, driven by the inability of the current standard of care, combination therapy with pegylated interferon alfa (PEG-IFNalpha) and ribavirin (RBV), to achieve a sustained virologic response (SVR) in a large proportion of patients and by the lack of approved alternative therapies for PEG-IFNalpha/RBV nonresponders and relapsers. Agents being developed against specific HCV viral proteins have recently been termed Specifically Targeted Antiviral Therapy for HCV (STAT-C). Preliminary data for several agents show they have high antiviral activity, especially when used in combination with PEG-IFNalpha, and are tolerable, but resistance mutations have been identified. Further study is needed to clarify the safety, tolerability, and efficacy of these compounds. Once established, the potential for shorter treatment strategies could then be evaluated. Other novel therapies in development that may improve both outcomes and tolerability include a prodrug of RBV and an albumin-modified IFNalpha. In conclusion, small molecule and novel therapies for HCV infection are showing promise in clinical trials, and research to develop new agents and optimize treatment regimens is ongoing.