How will we use the new antiviral agents for hepatitis B?

There are two licensed drugs for chronic hepatitis B virus (HBV), interferon alfa and lamivudine, with similar efficacy rates. Lamivudine is less expensive and better tolerated than interferon alfa and is the drug of choice for patients with decompensated cirrhosis and recurrent HBV infection after liver transplantation. The major problem with lamivudine monotherapy has been the emergence of drug-resistant HBV polymerase (YMDD) mutants. Thus, long-term use of lamivudine in other settings remains somewhat controversial. Alternative nucleoside analogues that are active against both wild-type and YMDD-mutant HBV are currently being tested. It is hoped that a combination of one or more of these agents with lamivudine will not only prove more effective than lamivudine alone but also decrease the rate of lamivudine resistance. Preliminary studies suggest that the combination of interferon and lamivudine is associated with an enhanced rate of virologic response when compared with either agent alone. From a theoretical perspective, the combination of interferon with one or more nucleoside analogues may be the most effective way to treat HBV infection in many clinical situations.