A ONE-YEAR TRIAL OF LAMIVUDINE FOR CHRONIC HEPATITIS-B

Background and Methods In preliminary trials, lamivudine, an oral nucl eoside analogue, has shown promise for the treatment of chronic hepati tis B. We conducted a one-year, double-blind trial of lamivudine in 35 8 Chinese patients with chronic hepatitis B. The patients were randoml y assigned to receive 25 mg of lamivudine (142 patients), 100 mg of la mivudine (143), or placebo (73) orally once daily. The pa tients under went liver biopsies before entering the study and after completing the assigned treatment regimen. The primary end point was a reduction of at least two points in the Knodell necroinflammatory score. Results He patic necroinflammatory activity improved by two points or more in 56 percent of the patients receiving 100 mg of lamivudine, 49 percent of those receiving 25 mg of lamivudine, and 25 percent of those receiving placebo (P<0.001 and P=0.001, respectively, for the comparisons of la mivudine treatment with placebo). Necroinflammatory activity worsened in 7 percent of the patients receiving 100 mg of lamivudine, 8 percent of those receiving 25 mg, and 26 percent of those receiving placebo. The 100-mg dose of lamivudine was associated with a reduced progressio n of fibrosis (P=0.01 for the com parison with placebo) and with the h ighest rate of hepatitis B e antigen (HBeAg) seroconversion (loss of H BeAg, development of antibody to HBeAg, and undetectable HBV DNA) (16 percent), the greatest suppression of HBV DNA (98 percent reduction at week 52 as compared with the base-line value), and the highest rate o f sustained normalization of alanine aminotransferase levels (72 perce nt). Ninety-six percent of the patients completed the study. The incid ence of adverse events was similar in all groups, and there were few s erious events. Conclusions In a one-year study, lamivudine was associa ted with substantial histologic improvement in many patients with chro nic hepatitis B. A daily dose of 100 mg was more effective than a dail y dose of 25 mg. (N Engl J Med 1998;339:61-8.) (C)1998, Massachusetts Medical Society.