Medical therapy of patients affected by HBeAg-negative chronic hepatitis B

Five agents are currently approved for the treatment of chronic hepatitis B: standard interferon-alpha (IFN-alpha), pegylated interferon-alpha 2a (PEG-IFN-alpha 2a), lamivudine, adefovir and entecavir. Each agent has inherent limitations. IFN and PEG-IFN-alpha 2a are effective in a minority of patients and have frequent side effects that limit their tolerability. The efficacy of lamivudine is limited by the emergence of drug-resistant hepatitis B virus (HBV) mutants, restricting its utility as a long-term therapy. Adefovir is well tolerated and associated with a low incidence of resistance but its antiviral effect is not optimal. Entecavir, which has been recently registered, has a more potent anti-viral effect but its long term efficacy and resistance profile is still not known. These antivirals induce a sustained response after withdrawal of therapy in only a minority of patients and therefore the treatment needs to be indefinitely administered in the majority of patients. After a brief summary of the natural history of chronic hepatitis B in order to understand the indications and the objectives of therapy, this review focuses on treatment of HBeAg-negative chronic hepatitis B with IFN and PEG-IFN-alpha 2a.