拉米夫定治疗慢性乙型肝炎的一年期试验。亚洲肝炎拉米夫定研究组。

A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group.

作者信息

Lai C L, Chien R N, Leung N W, Chang T T, Guan R, Tai D I, Ng K Y, Wu P C, Dent J C, Barber J, Stephenson S L, Gray D F

机构信息

Department of Medicine, Queen Mary Hospital, Hong Kong, China.

出版信息

N Engl J Med. 1998 Jul 9;339(2):61-8. doi: 10.1056/NEJM199807093390201.

DOI:10.1056/NEJM199807093390201

PMID:9654535

Abstract

BACKGROUND AND METHODS

In preliminary trials, lamivudine, an oral nucleoside analogue, has shown promise for the treatment of chronic hepatitis B. We conducted a one-year, double-blind trial of lamivudine in 358 Chinese patients with chronic hepatitis B. The patients were randomly assigned to receive 25 mg of lamivudine (142 patients), 100 mg of lamivudine (143), or placebo (73) orally once daily. The patients underwent 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

Hepatic 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 lamivudine 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 progression of fibrosis (P=0.01 for the comparison with placebo) and with the highest rate of hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg, 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 of sustained normalization of alanine aminotransferase levels (72 percent). Ninety-six percent of the patients completed the study. The incidence of adverse events was similar in all groups, and there were few serious events.

CONCLUSIONS

In a one-year study, lamivudine was associated with substantial histologic improvement in many patients with chronic hepatitis B. A daily dose of 100 mg was more effective than a daily dose of 25 mg.

摘要

背景与方法

在初步试验中，口服核苷类似物拉米夫定对慢性乙型肝炎的治疗显示出前景。我们对358例中国慢性乙型肝炎患者进行了一项为期一年的拉米夫定双盲试验。患者被随机分配口服每日一次25毫克拉米夫定（142例患者）、100毫克拉米夫定（143例）或安慰剂（73例）。患者在进入研究前及完成指定治疗方案后接受肝活检。主要终点是Knodell坏死性炎症评分至少降低2分。

结果

接受100毫克拉米夫定的患者中，56%的患者肝脏坏死性炎症活动改善2分或更多；接受25毫克拉米夫定的患者中，49%改善；接受安慰剂的患者中，25%改善（拉米夫定治疗组与安慰剂组比较，P值分别<0.001和P = 0.001）。接受100毫克拉米夫定的患者中，7%的患者坏死性炎症活动恶化；接受25毫克的患者中，8%恶化；接受安慰剂的患者中，26%恶化。100毫克剂量的拉米夫定与纤维化进展减缓相关（与安慰剂比较，P = 0.01），且乙肝e抗原（HBeAg）血清学转换率最高（HBeAg消失、出现抗HBeAg抗体且检测不到HBV DNA）（16%），对HBV DNA的抑制作用最大（与基线值相比，第52周降低98%），谷丙转氨酶水平持续正常化率最高（72%）。96%的患者完成了研究。所有组不良事件发生率相似，严重事件较少。