Gastroenterologist and Hepatologist/Clinical Pharmacologist, Clinical Senior Lecturer in Medicine, University of Otago, Christchurch, Christchurch Hospital, Private Bag 4710, Christchurch 8140, New Zealand.
Treatment of chronic hepatitis C (HCV) is currently undergoing a significant change. Traditional interferon-based therapy has been limited by both efficacy and tolerability, and many direct acting antiviral (DAA) drugs are emerging. Sofosbuvir (GS-7977) is a HCV NS5B nucleotide polymerase inhibitor that has now been evaluated extensively in phase II and III interferon-free clinical trials. The focus of this review is on the clinical potential of sofosbuvir in the treatment of HCV. Sofosbuvir has a pan-genotypic effect on HCV, although viral genotype-specific differences in sustained virological response (SVR) have emerged in phase III clinical trials. Sofosbuvir has been studied both as dual therapy with ribavirin and also as triple therapy with either NS5A inhibitors or a protease inhibitor. High rates of SVR have been reported with these interferon-free combinations, particularly with genotypes 1 and 2, and the safety profile has been very favourable in both cirrhotic and noncirrhotic patients, without issues of viral resistance. Interferon-free, once-daily treatment of HCV is now becoming a reality.