We conducted a randomized, placebo-controlled clinical study evaluating
famciclovir (500 mg 3 times daily and 1.5 g once daily) for 1 year (6 months post-treatment follow-up) in patients with
chronic hepatitis B e antigen (
HBeAg)-positive hepatitis B virus (HBV)
infection. The study was conducted in 80 centers in North America, Europe, and Australia/New Zealand. A total of 417 patients with histologically documented
chronic hepatitis B (histologic activity index [HAI] 9.5-11.0) received
famciclovir (500 mg 3 times daily or 1.5 g once daily) or placebo.
Famciclovir 500 mg 3 times daily significantly reduced HBV
DNA and median HAI scores versus placebo. By week 8, median HBV
DNA decreased from 1,645 to 283 MEq/mL (
famciclovir 500 mg 3 times daily) and from 1,147 to 304 MEq/mL (
famciclovir 1.5 g once daily), while increasing for placebo (1,617 to 1,685 MEq/mL). Median change in HBV
DNA at the end of
therapy was -76% (
famciclovir 500 mg 3 times daily; P <.01) and -60% (
famciclovir 1.5 g once daily; P =.25) versus -37% for placebo. Median change in HAI was -1.5 points (
famciclovir 500 mg 3 times daily; P =.02) and -1.0 point (
famciclovir 1.5 g once daily; P =.35) and zero for placebo. Fifty percent of patients receiving
famciclovir 500 mg 3 times daily (P =.07) and 43% receiving 1.5 g once daily (P =.41) experienced >/=2 points improvement in HAI versus 37% for placebo. Nine percent of patients treated with
famciclovir 500 mg 3 times daily underwent anti-
HBeAg seroconversion with undetectable HBV
DNA at end of follow-up versus 3% in the placebo group (P =.05).
Famciclovir was well tolerated; the incidence of post-treatment
alanine transaminase (ALT) elevations was comparable with placebo. In conclusion,
famciclovir 500 mg 3 times daily gave modest suppression of viral replication, but translated into significant histologic improvement in median HAI score at 1 year.