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.