See Articles on Pages 631 and 640. N o challenge in clinical hepatology is as great today as the management of patients with chronic hepatitis C who have failed to respond to an adequate course of antiviral therapy. At present, the optimal regimen is a combination of peginterferon and ribavirin. 1 When given for 24 or 48 weeks, this combination results in a sustained eradication of hepatitis C virus (HCV) and a long-term remission of the disease in at least 75% of patients with genotype 2 or 3 HCV infection and in 40%-50% of those with genotype 1. 2,3 Although impressive, these sustained virological response (SVR) rates leave as many as half of patients without benefit and with no means of ameliorating the subsequent course of the disease. Despite the importance of chronic hepatitis C (the leading cause of end-stage liver disease and need for liver transplantation in the Western world) and the intensity of the research on this viral infection, there have been no further improvements in response rates to therapy in many years. When will this change?
In this issue of HEPATOLOGY, two original articles provide exciting new results on a novel orally available antiviral agent that has potent effects against HCV in vitro and in vivo. 4,5 VX-950, now known as telaprevir, is a peptide-mimetic drug that was developed with structurebased drug design. 6 Telaprevir is a specific, reversible inhibitor of the HCV genotype 1 serine protease encoded by the nonstructural 3 and 4A region of the viral genome. This protease is essential for HCV replication, 7 and its inhibition in cell culture systems results in marked suppression of viral replication. 6,7 In humans, telaprevir is orally available and causes a rapid and marked decrease in serum HCV RNA levels. 8 In phase Ia studies using various doses and schedules, a dose of 750 mg of telaprevir given every 8 hours resulted in rapid 3-5 log 10 decreases in Abbreviations: HCV, hepatitis C virus; SVR, sustained virological response.