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 i nfection with the hepatitis B virus (HBV). Antiviral chemotherapy remains t he 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 hep atitis B infection has proven to be extremely challenging, the result of bo th virus- and host-dependent factors, which will be reviewed in this articl e, Past attempts to treat chronic hepatitis B infection using nucleoside an alogues were disappointing, but more recently, several nucleoside (or nucle otide) analogues have been identified that are potent and selective inhibit ors of HBV replication, These agents fall into two broad categories: (1) nu cleoside/nucleotides that have modified sugar residues in either cyclic or acyclic configurations and (2) stereoisomers of nucleosides in the "unnatur al" L-configuration, Of the analogues that have been used clinically, repre sentatives of the first category are purine derivatives, e.g., adefovir dip ivoxil and famciclovir, whereas representatives of the second category are pyrimidine derivatives, such as lamivudine.