The science, economics, and effectiveness of combination therapy for hepatitis C

The ideal management of hepatitis C infection would be to target treatment to those with progressive disease with drugs that are effective, inexpensive, and with few side effects. What is the evidence that combination antiviral therapy improves the therapeutic efficacy for this complex group of patients, and what are the implications? Hepatitis C virus (HCV) is a small enveloped RNA virus belonging to the family Flaviviridae. Representative population based prevalence data are not available in many countries, including the UK; the prevalence in the USA is 1.8%.1 The majority of HCV infections in developed and developing countries are or have been caused by intravenous drug use, transfusion of unscreened blood and blood products, nosocomial transmission from inadequately sterilised instruments or unsafe injections, chronic haemodialysis, and possibly high risk sexual practices. Infection with hepatitis C does not usually resolve, and 60–80% of acute infections persist. Chronic hepatitis can cause progressive fibrosis of the liver, leading to cirrhosis in 20–30%.2Cirrhosis rarely becomes detectable before the second or third decade of infection.3 Hepatic fibrosis may occur at varying rates. However, male sex, higher alcohol use, older age at the time of infection (or perhaps index biopsy), duration of infection, and a higher necro-inflammatory score at the initial liver biopsy are probable predictors of increasing fibrosis. The prediction of outcome is facilitated if fibrosis is already present. Coinfection with hepatitis B virus and/or HIV may lead to more severe disease.4 5 Rates of fibrosis have been estimated but the risk of eventual progression from mild disease to increasing fibrosis and eventual cirrhosis has not been adequately assessed in prospective studies. It is also unknown whether the rate of progression is linear. An increase in the incidence of hepatocellular carcinoma in the USA and Japan has been ascribed to hepatitis …