HEPATITIS-B - TREATMENT FOR THE 21ST-CENTURY

Hepatitis B virus (HBV) infection constitutes a worldwide public healt h problem, causing both acute and chronic liver infections. Although a vaccine has been developed that is effective in preventing HBV infect ion, this is of no benefit to the estimated 350 million carriers of th e virus. Chronic hepatitis B infection may lead to cirrhosis of the li ver and hepatocellular carcinoma. Therefore, there is a clear need for antiviral therapy. Alpha interferon was the first therapeutic agent u sed against HBV infection. However, its lack of efficacy in many patie nts and significant adverse event profile has prompted the development of alternative therapies. Nucleoside analogues are currently being in vestigated as potential anti-HBV agents, with two compounds, famciclov ir and lamivudine, undergoing Phase III clinical trials of long-term u se. In preclinical studies using the Pekin duck model for hepatitis B, both compounds have been found to reduce the amount of serum duck HBV DNA to sub-detectable levels during therapy. However, once therapy wa s stopped, the virus returned to pretreatment levels, making longterm treatment necessary. In clinical studies in chronic hepatis B patients , treatment with these agents also resulted in a significant reduction of HBV DNA levels but, again, the return of HBV DNA after discontinui ng treatment indicates the need for long-term therapy. The need for lo ng-term treatment means that the virus may develop resistance to the a ntiviral agents. Resistance mutations to both famciclovir and lamivudi ne are now being reported after treatment of chronic HBV infection wit h these agents. Combination therapy may be a strategy to overcome the development of resistance. Therapeutic vaccines and new antiviral agen ts are also being developed.