Antiviral therapy for hepatitis B virus infections: new targets and technical challenges

There are presently only two licensed therapies for treating liver disease caused by infection with the hepatitis B virus (HBV). These are interferon-alpha and lamivudine. Neither agent was specifically developed as an antiviral compound for treating patients infected with HBV. Both therapies are limited in the clinic by a low response rate and in the case of lamivudine, selection of drug-resistant mutants, whilst troublesome side effects limit the use of interferon-alpha. Several promising nucleoside/nucleotide analogues are undergoing clinical trials, including adefovir dipivoxil and entecavir, both of which appear to be active against lamivudine- resistant HBV. In addition to these nucleoside/nucleotide analogues, it will be important to develop new agents with different modes of action, which can be added to the antiviral cocktails that will be required to adequately suppress and hopefully eliminate HBV replication.