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

Background/Aims: Famciclovir, an orally available nucleoside analogue with potent in vitro activity against HBV, is being investigated for treatment o f chronic hepatitis B. Methods: 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 p ost-treatment observation, and 16 weeks open-label treatment. More than 90% of patients had previously received alpha-interferon or had baseline chara cteristics indicating a high likelihood of poor response to alpha-interfero n, Results: Famciclovir induced rapid, dose-dependent suppression of viral rep lication and reduction in alanine aminotransferase (ALT), with greatest eff icacy in the 500-mg tid treatment group. HBV DNA reduction was maintained t hroughout the treatment period. ALT also steadily declined during the treat ment period. Approximately 40% of patients with pretreatment ALT>upper limi t of normal (ULN) receiving famciclovir 500 mg tid, experienced sustained n ormalization of ALT at the end of the 8-month followup. Anti-HBe seroconver sion occurred more frequently in patients receiving famciclovir 500 mg tid compared with placebo (p=0.04), Famciclovir was generally well tolerated; t he incidence of adverse events was comparable to placebo. Exacerbation of l iver disease or serious ALT flares were not observed. Conclusion: Famciclovir 500 mg three times daily may offer an alternative t o alpha-interferon for treatment for chronic hepatitis B, Anti-HBe seroconv ersion in the famciclovir 500-mg tid group suggests that 16 weeks treatment has the potential for HBV clearance. Further studies with a longer treatme nt duration are warranted.