Antiviral chemotherapy for the treatment of hepatitis B virus infections.

Approximately 5% of the world's human population have an increased risk for developing liver cancer and cirrhosis as a direct consequence of chronic infection with the hepatitis B virus (HBV). Antiviral chemotherapy remains the only option for controlling infection in these individuals, for whom the current licensed hepatitis B vaccines provide no benefit. Interferon (IFN)-alpha has proven benefit in a well-defined group of those with hepatitis B but has made little impact on the global burden of chronic liver disease. The development of more effective chemotherapy for treatment of chronic hepatitis B infection has proven to be extremely challenging, the result of both virus- and host-dependent factors, which will be reviewed in this article. Past attempts to treat chronic hepatitis B infection using nucleoside analogues were disappointing, but more recently, several nucleoside (or nucleotide) analogues have been identified that are potent and selective inhibitors of HBV replication. These agents fall into two broad categories: (1) nucleoside/nucleotides that have modified sugar residues in either cyclic or acyclic configurations and (2) stereoisomers of nucleosides in the "unnatural" L-configuration. Of the analogues that have been used clinically, representatives of the first category are purine derivatives, e.g., adefovir dipivoxil and famciclovir, whereas representatives of the second category are pyrimidine derivatives, such as lamivudine.