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 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.
de Man
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RA
University Hospital Rotterdam, Rotterdam, The Netherlands. deman@mdl.azr.nl
Marcellin
P
P
Habal
F
F
Desmond
P
P
Wright
T
T
Rose
T
T
Jurewicz
R
R
Young
C
C
D015075:2-Aminopurine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D004311:Double-Blind Method; D000077595:Famciclovir; D005260:Female; D006513:Hepatitis B e Antigens / Q000032:analysis*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D015075:2-Aminopurine; D000410:Alanine Transaminase; D000077595:Famciclovir