Famciclovir in chronic hepatitis B: results of a dose-finding study

Famciclovir, an orally available nucleoside analogue with potent in vitro activity against HBV, is being investigated for treatment of chronic hepatitis B.

A dose-finding study was conducted in patients with hepatitis B e antigen present in serum. Patients received famciclovir 125 mg, 250 mg, 500 mg three times daily (tid) or placebo for 16 weeks, followed by 8 months post-treatment observation, and 16 weeks open-label treatment. More than 90% of patients had previously received alpha-interferon or had baseline characteristics indicating a high likelihood of poor response to alpha-interferon.

Famciclovir induced rapid, dose-dependent suppression of viral replication and reduction in alanine aminotransferase (ALT), with greatest efficacy in the 500-mg tid treatment group. HBV DNA reduction was maintained throughout the treatment period. ALT also steadily declined during the treatment period. Approximately 40% of patients with pretreatment ALT>upper limit of normal (ULN) receiving famciclovir 500 mg tid, experienced sustained normalization of ALT at the end of the 8-month follow-up. Anti-HBe seroconversion occurred more frequently in patients receiving famciclovir 500 mg tid compared with placebo (p=0.04). Famciclovir was generally well tolerated; the incidence of adverse events was comparable to placebo. Exacerbation of liver disease or serious ALT flares were not observed.

Famciclovir 500 mg three times daily may offer an alternative to alpha-interferon for treatment for chronic hepatitis B. Anti-HBe seroconversion in the famciclovir 500-mg tid group suggests that 16 weeks treatment has the potential for HBV clearance. Further studies with a longer treatment duration are warranted.