Antiviral therapy of hepatitis B virus infection: Blocking viral gene expression

Hepatitis B virus (HBV) infection is a major cause of chronic viral hepatitis and liver cirrhosis worldwide. HBV has been characterized in great detail and can be specifically identified by serological and molecular techniques. Chronic hepatitis B frequently progresses to liver cirrhosis with its clinical sequelae and is associated with the development of hepatocellular carcinoma (HCC). Strategies aimed at the prevention of liver cirrhosis include primary prevention of HBV infection by various measures as well as secondary prevention by therapy of acute or chronic hepatitis B as precursors of liver cirrhosis and HCC development. For the treatment of chronic hepatitis B interferon-alpha or -beta are the only drugs currently available for clinical use in selected patients. Given their limited efficacy, combination therapies of interferon-alpha or -beta with synthetic antiviral agents or other drugs as well-as gene therapy strategies are presently being explored. These molecular strategies are designed to specifically deliver antiviral nucleic acids to infected cells, thereby improving therapeutic efficacy and reducing extrahepatic side-effects.