Oral direct-acting antiviral therapy for hepatitis C

Chronic hepatitis C infection is a major cause of chronic liver disease, cirrhosis and liver cancer in much of the Western world [1,2] and poses a significant public health problem. The early institution of appropriate treatment to prevent the complications of hepatitis C is the cornerstone of management. At the start of the 1990s, treatment with interferon alpha monotherapy was considered to be the gold standard of treatment for hepatitis C infection despite a poor cure rate of less than 20% [3]. This bleak statistic reinforced a negative perception, among clinicians, of the natural history of the disease and led to the widespread view of infection with the hepatitis C virus (HCV) as being a (largely) incurable, chronic condition with inevitable progression to cirrhosis and, possibly, hepatocellular carcinoma in a significant percentage of patients [4]. However, the advent of two new drugs in the 1990’s hailed a paradigm shift in clinicians’ attitudes towards hepatitis C infection, from both a therapeutic and prognostic perspective, when it was shown that: firstly, the addition of ribavirin to standard interferon monotherapy significantly increased the rate of sustained virological response (SVR) to around 40-45% [5]; and, secondly, the combination of pegylated interferon and ribavirin boosted SVR rates to around 55% for patients with HCV genotype 1 and 80% for patients with HCV genotypes 2 and 3 [6,7].