Lamivudine as initial treatment for chronic hepatitis B in the United States

Background Although the nucleoside analogue lamivudine has shown promise in patients with chronic hepatitis B, long-term data on patients from the Uni ted States are lacking. Methods We randomly assigned previously untreated patients with chronic hep atitis B to receive either 100 mg of oral lamivudine or placebo daily for 5 2 weeks. We then followed them for an additional 16 weeks to evaluate post- treatment safety and the durability of responses. The primary end point wit h respect to efficacy was a reduction of at least 2 points in the score on the Histologic Activity Index. On this scale, scores can range from 0 (norm al) to 22 (most severe abnormalities). Results Of the 143 randomized patients, 137 were included in the efficacy a nalysis: 66 in the lamivudine group and 71 in the placebo group. The other six patients were excluded at the base-line visit because of the absence of a documented history of hepatitis B surface antigen for at least six month s. After 52 weeks of treatment, lamivudine recipients were more likely than placebo recipients to have a histologic response (52 percent vs. 23 percen t, P<0.001), loss of hepatitis B e antigen (HBeAg) in serum (32 percent vs. 11 percent, P=0.003), sustained suppression of serum hepatitis B virus (HB V) DNA to undetectable levels (44 percent vs. 16 percent, P<0.001), and sus tained normalization of serum alanine aminotransferase levels (41 percent v s. 7 percent, P<0.001), and they were less likely to have increased hepatic fibrosis (5 percent vs. 20 percent, P=0.01). Lamivudine recipients were al so more likely to undergo HBeAg seroconversion, defined as the loss of HBeA g, undetectable levels of serum HBV DNA, and the appearance of antibodies a gainst HBeAg (17 percent vs. 6 percent, P=0.04). HBeAg responses persisted in most patients for 16 weeks after the discontinuation of treatment. Lamiv udine was well tolerated. Self-limited post-treatment elevations in serum a lanine aminotransferase were more common in lamivudine recipients: 25 perce nt had serum alanine aminotransferase levels that were at least three times base-line levels, as compared with 8 percent of placebo recipients (P=0.01 ). The clinical condition of all patients remained stable during the study. Conclusions In U.S. patients with previously untreated chronic hepatitis B, one year of lamivudine therapy had favorable effects on histologic, virolo gic, and biochemical features of the disease and was well tolerated. HBeAg responses were usually sustained after treatment. (N Engl J Med 1999;341:12 56-63.) (C)1999, Massachusetts Medical Society.