Entecavir: a new treatment option for chronic hepatitis B

Because of the slow kinetics of viral clearance and the spontaneous genetic variability of hepatitis B virus (HBV), antiviral therapy of chronic hepatitis B remains a clinical challenge. Despite the recent development of lamivudine, adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic HBV infection, there is still a major need for new antiviral compounds. Entecavir, a guanosine analog, has been recently approved in US for the therapy of chronic hepatitis B and its registration is expected soon in Europe. Extensive studies have been performed to characterize its antiviral activity in enzymatic and tissue culture models, as well as in animal models of HBV infection. In clinical trails, entecavir administration was associated with a significantly more potent viral suppression compared to lamivudine, and a significant advantage in terms of biochemical and histological improvement compared to lamivudine. Entecavir was tolerated as well as lamivudine in these phase III trials. No case of resistance was detected after two years of therapy in nucleoside naive patients. Treatment of patients with lamivudine failure requires a higher dosage of entecavir and induces a significant decline in viraemia levels. However, 10% of these patients developed entecavir resistance after two years of therapy. The availability of entecavir as a new treatment option is providing clinicians more choice to keep both viral replication and liver disease under control. This provides new hope for improved treatment concepts for chronic HBV infection.