Overview of hepatitis C infection, molecular biology, and new treatment

Abstract

The World Health Organization estimates that 71 million people worldwide have chronic hepatitis C viral infection. A major challenge is overall lack of public awareness of hepatitis C, particularly among infected people of their infection status. Chronic hepatitis C infection is associated with advanced liver disease, is the main cause of hepatocellular carcinoma and causes many extra-hepatic manifestations. The existence of seven viral genotypes complicates targeting of treatment. Recent years have seen the approval of many direct acting antivirals targeted at hepatitis C virus non-structural proteins. These have revolutionized therapy as they allow achievement of extremely high sustained virologic responses. Of great significance is the development of pan-genotypic drug combinations, including the NS3/4A-NS5A inhibitor combinations sofosbuvir–velpatasvir and glecaprevir–pibrentasvir. However, resistance-associated mutations can result in failure of these treatments in a small number of patients. This, combined with the high costs of treatment, highlights the importance of continued research into effective anti-hepatitis C therapies, for example aimed at viral entry. Recent developments include identification of the potential of low-cost anti-histamines for repurposing as inhibitors of hepatitis C viral entry. In this review we focus on molecular biology of hepatitis C virus, and the new developments in hepatitis C treatment. Keywords: Hepatitis, Direct-acting antiviral, Sofosbuvir, Resistance-associated variant, NS5A