A randomized, placebo-controlled study to evaluate the efficacy of 12-month famciclovir treatment in patients with chronic hepatitis B e antigen-positive hepatitis B

We conducted a randomized, placebo-controlled clinical study evaluating fam ciclovir (500 mg 3 times daily and 1.5 g once daily) for 1 year (6 months p ost-treatment follow-up) in patients with chronic hepatitis B e antigen (HB eAg)-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 (histologi c 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 signific antly reduced HBV DNA and median HAI scores versus placebo. By week 8, medi an HBV DNA decreased from 1,645 to 283 MEq/mL (famciclovir 500 mg 3 times d aily) and from 1,147 to 304 MEq/mL (famciclovir 1.5 g once daily), while in creasing for placebo (1,617 to 1,685 MEq/mL). Median change in HBV DNA at t he 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. Media n 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 placeb o. Fifty percent of patients receiving famciclovir 500 mg 3 times daily (P = .07) and 43% receiving 1.5 g once daily (P = .41) experienced greater tha n or equal to 2 points improvement in HAI versus 37% for placebo. Nine perc ent of patients treated with famciclovir 500 mg 3 times daily underwent ant i-HBeAg sero-conversion with undetectable HBV DNA at end of follow-up versu s 3% in the placebo group (P = .05). Famciclovir was well tolerated; the in cidence of post-treatment alanine transaminase (ALT) elevations was compara ble with placebo. In conclusion, famciclovir 500 mg 3 times daily gave mode st suppression of viral replication, but translated into significant histol ogic improvement in median HAI score at 1 year.