Combination and newer therapies for chronic hepatitis B.

Worldwide the need for effective therapy for chronic hepatitis B is similar to that for chronic hepatitis C. Current licensed treatment for chronic hepatitis B (interferon (IFN)-alpha, lamivudine) does not significantly alter the natural history of the disease because the frequency of sustained response is too low; however, a sustained response to antiviral therapy improves survival. Conversion of active chronic hepatitis B to the inactive hepatitis B carrier state (persistently HBeAg-negative, HBV-DNA < 10(5) copies/mL and alanine aminotransferase (ALT) normal) is the major therapeutic goal. If present 6-12 months after stopping treatment, a sustained response is assumed. Clinical benefit is also likely if HBV-DNA levels < 10(5) copies/mL and ALT normality are being maintained long-term by antiviral therapy. New drugs are adefovir, entecavir, and pegylated IFN. The two nucleoside analogs are active against lamivudine-resistant hepatitis B and are as yet not associated with resistance. Peg-IFN has higher efficacy than standard IFN; its tolerance is similar. Combination therapy appears most effective: IFN-lamivudine combination for induction of a sustained response, and lamivudine-adefovir for long-term antiviral therapy. Uncertainty exists whether the additional effect outweighs the burden of adverse effects and cost. Chronic hepatitis B affects a rather heterogeneous patient population. Differentiation based on HBeAg status is fading with emergence of categorization based on disease stage and immune competence.