Adefovir Dipivoxil as a Treatment for Hepatic Failure Caused by Lamivudine-Resistant HBV Strains

Hepatitis B virus (HBV) infection is a serious worldwide problem because it is one of the major causes of cirrhosis and hepatocellular carcinoma in endemic areas. The number of people with chronic HBV infection is 350 million globally (1). Until recently, the therapeutic option for chronic HBV infection has been limited to interferon. Seroconversion from hepatitis B e antigen (HBeAg) to anti-hepatitis B e antibody (anti-HBe) occurs in up to about 40% of patients treated with interferon monotherapy (2–4). Recently, lamivudine, a nucleoside analogue, has become the main therapeutic option for chronic HBV infection. Some clinical trials showed that lamivudine suppressed HBV replication effectively and induced histological improvement (5–7). However, the prolonged therapy with lamivudine has been associated with the emergence of drug-resistant viruses with the mutations in the polymerase gene coding for the YMDD (tyrosine, methionine, aspartate, aspartate) motif (8, 9). The lamivudine-resistant HBV strains have been observed in 14 to 32% of patients undergoing a 1-year treatment regimen of 100 mg daily (6, 7). Several new nucleoside analogues are now under development. Adefovir dipivoxil, a prodrug of the acyclic deoxyadenosine monophosphate analogue adefovir, displays potent antiviral activity against HBV (10, 11) and an in vitro study demonstrated the antiviral activity to be against both wild-type and lamivudine-resistant strains of