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

被引:1075
作者
Dienstag, JL [1 ]
Schiff, ER
Wright, TL
Perrillo, RP
Hann, HWL
Goodman, Z
Crowther, L
Condreay, LD
Woessner, M
Rubin, M
Brown, NA
机构
[1] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA
[2] Massachusetts Gen Hosp, Liver Biliary Pancreas Ctr, Boston, MA 02114 USA
[3] Harvard Univ, Sch Med, Dept Med, Boston, MA USA
[4] Univ Miami, Med Ctr, Ctr Liver Dis, Miami, FL 33152 USA
[5] Vet Affairs Med Ctr, Miami, FL 33125 USA
[6] Vet Affairs Med Ctr, Div Gastroenterol, San Francisco, CA 94121 USA
[7] Alton Ochsner Med Fdn & Ochsner Clin, Div Gastroenterol, New Orleans, LA 70121 USA
[8] Thomas Jefferson Univ, Jefferson Med Coll, Div Gastroenterol & Hepatol, Philadelphia, PA 19107 USA
[9] Armed Forces Inst Pathol, Washington, DC 20306 USA
[10] Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA
关键词
D O I
10.1056/NEJM199910213411702
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Although the nucleoside analogue lamivudine has shown promise in patients with chronic hepatitis B, long-term data on patients from the United States are lacking. Methods We randomly assigned previously untreated patients with chronic hepatitis B to receive either 100 mg of oral lamivudine or placebo daily for 52 weeks. We then followed them for an additional 16 weeks to evaluate post-treatment safety and the durability of responses. The primary end point with 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 (normal) to 22 (most severe abnormalities). Results Of the 143 randomized patients, 137 were included in the efficacy analysis: 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 months. After 52 weeks of treatment, lamivudine recipients were more likely than placebo recipients to have a histologic response (52 percent vs. 23 percent, 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 (HBV) DNA to undetectable levels (44 percent vs. 16 percent, P<0.001), and sustained normalization of serum alanine aminotransferase levels (41 percent vs. 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 also more likely to undergo HBeAg seroconversion, defined as the loss of HBeAg, undetectable levels of serum HBV DNA, and the appearance of antibodies against HBeAg (17 percent vs. 6 percent, P=0.04). HBeAg responses persisted in most patients for 16 weeks after the discontinuation of treatment. Lamivudine was well tolerated. Self-limited post-treatment elevations in serum alanine aminotransferase were more common in lamivudine recipients: 25 percent 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, virologic, and biochemical features of the disease and was well tolerated. HBeAg responses were usually sustained after treatment. (N Engl J Med 1999;341:1256-63.) (C)1999, Massachusetts Medical Society.
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页码:1256 / 1263
页数:8
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