Developments in the treatment of chronic hepatitis C

Abstract

Hepatitis C virus is the most common chronic, blood-bourne infection, affecting 170 million people worldwide, approximately 3% of the global population. Of those infected with hepatitis C virus, 50 - 85% will develop chronic hepatitis C. Although hepatitis C is primarily a disease of the liver, a diagnosis is currently defined by the presence of the hepatitis C virus and treatment success is defined by the clearance of the virus. IFN-alpha is currently the mainstay of chronic hepatitis C therapy; the antiviral and anti-inflammatory components of IFN target both the infectious and the hepatic manifestations of the disease. However, even in combination with ribavirin, interferon therapy is not fully efficacious. Recently, the search for a more effective treatment has led investigators to optimise interferon therapy by developing pegylated interferons. Challenges facing our current treatment of hepatitis C virus include lack of efficacy in patients with difficult-to-treat disease, such as patients with cirrhosis or infected with hepatitis C virus genotype 1 (who represent a majority of US hepatitis C virus infections), the toxicity of combination therapy, the expense and difficulty of therapy and the poor reception of these treatments by many patients. The development of new hepatitis C antiviral agents is critical to our management of this disease. A number of approaches are under investigation, including long-acting interferons, immunomodulators, antifibrotics, specific hepatitis C virus-derived enzyme inhibitors, drugs that either block hepatitis C virus antigen production from RNA or prevent normal processing of hepatitis C virus proteins and other molecular approaches to treating hepatitis C virus, such as ribozymes and antisense oligonucleotides.