National Institutes of Health Bethesda, MD 20892

Not since the initial cloning of the hepatitis C virus (HCV) in 1989 and the subsequent development of assays to detect silent carriers and protect the blood supply, have data on this infection been so exciting. Before 1990, HCV was an incurable, prevalent chronic infection and had only a 10% cure rate with early interferon monotherapy. Sustained virologic response (SVR) rates—which are tantamount to cure—increased to approximately 25% by adding ribavirin and 45% when pegylated interferon was combined with ribavirin.

In 2011, the first HCV-specific protease inhibitors were licensed after clinical trials showed that these drugs, combined with pegylated interferon and ribavirin, could achieve close to 70% SVR for patients with genotype 1 infections Further, a small clinical trial that added a polymerase inhibitor (quadruple therapy) achieved 90% SVR. More amazing, a Japanese trial that used only 2 oral agents (protease plus NS5A inhibitor) also demonstrated a 90% cure rate,albeit in only 10 patients. Such dramatic cure rates for genotype 1 infections far exceed prior expectations and portend a paradigm shift in HCV therapy that may eventuate in interferon-sparing regimens with low toxicity and high compliance.