Combination chemotherapy for hepatitis B virus: The final solution?

Despite the widespread use of effective vaccines, hepatitis B virus (HBV) infection continues to be a global health problem, responsible for 1.2 million deaths annually.1-3 Chemotherapy remains the only option for chronic carriers of HBV, the number of whom is expected to approach 400 million by the end of year 2000.1-3 Although many treatment strategies have been tested during the past 30 years, none has proven consistently successful.1-4 Interferon alfa (IFN-a) was the only drug approved for chronic HBV infection in most countries until very recently. Patients who have high pretreatment serum alanine transaminase and low serum HBV-DNA concentrations usually respond favorably to IFN-a, but overall the results are poor and adverse effects are relatively common during treatment.5 Attempts to control HBV with antiviral nucleoside analogues, either alone or in combination with IFN, have been similarly disappointing because of toxicity and/or lack of efficacy.3,4,6 This gloomy outlook has changed dramatically during the past few years as a result of an improved understanding of HBV replication and pathogenesis7 and development of new anti-HBV agents.2,3 Of the new agents, only lamivudine has been approved for use in chronic HBV infection,8 although famciclovir has undergone phase III development9 and has been used successfully in transplant patients with recurrent HBV infection10 and in HBe antigen–negative chronic hepatitis B.11 Phase II/III clinical trials of several other agents are about to start or are already underway.2,3,6