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

• Published in: Journal of hepatology 2000-06, Vol.32 (6), p.1011-1018
• Main Authors: Trépo, Christian, Jezek, Pavel, Atkinson, Gillian, Boon, Ron, Young, Clarence
• Format: Article
• Language: English
• Subjects: 2-Aminopurine - administration & dosage; 2-Aminopurine - adverse effects; 2-Aminopurine - analogs & derivatives; 2-Aminopurine - therapeutic use; Adult; Alanine Transaminase - blood; Alanine transferase; Antiviral Agents - administration & dosage; Antiviral Agents - adverse effects; Antiviral Agents - therapeutic use; Chronic hepatitis B; DNA, Viral - analysis; Dose-finding study; Dose-Response Relationship, Drug; Double-Blind Method; Famciclovir; Female; HBV DNA; Hepacivirus - drug effects; Hepacivirus - genetics; Hepacivirus - immunology; Hepacivirus - physiology; Hepatitis Antibodies - analysis; Hepatitis B e Antigens - immunology; Hepatitis B, Chronic - blood; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - virology; Humans; Male; Middle Aged; Nucleoside analogue; Seroconversion; Treatment Outcome; Virus Replication - drug effects
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/S0168-8278(00)80106-3

Background/Aims: Famciclovir, an orally available nucleoside analogue with potent in vitro activity against HBV, is being investigated for treatment of 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 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. Results: 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. Conclusion: 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.