摘要
目的 评估拉米夫定长期治疗慢性乙型肝炎的疗效和安全性 ,以及治疗过程中产生病毒变异的临床影响。方法 系多中心的双盲、随机、安慰剂对照的临床试验。 42 9例HBsAg和HBeAg阳性的慢性乙型肝炎 ,按 3∶1随机分成拉米夫定治疗组和对照组 ,分别服用拉米夫定 1 0 0mg/d和安慰剂共 1 2周 ,此后所有病人均服用拉米夫定 ,共观察 2年。结果 治疗 1 2周 ,拉米夫定组血清HBVDNA累计阴转率 (<1 .6pg/ml)为 92 .2 % ,安慰剂组仅为 1 4 .1 % (P <0 .0 1 )。第 52周末 ,拉米夫定组和安慰剂 /拉米夫定组的阴转率分别为 71 .0 %和 77.7% (P >0 .0 5)。在第 2年末 ,除了发生YMDD变异的病人外 ,HBVDNA的均值持续低于最低测出值。拉米夫定治疗后 ,部分病人出现HBeAg阴转和HBeAg(- ) /抗HBe(+)血清转换 ,其发生与治疗前ALT水平和疗程有关。第 2年治疗结束时 ,血清ALT >1ULN(正常值上限 )、>2ULN和 >5ULN病人的HBeAg阴转率分别为 2 6 .8%、35.6 %和 55 .6 % ;血清转换率分别为 1 1 .4%、2 2 .2 %和33 .3 %。治疗前ALT增高者 2 0 2例 ,2年后 50 .3 %保持正常 ;ALT正常者 2 2 4例 ,83 %ALT仍正常。第 1年和第 2年时出现YMDD变异的发生率分别为 1 4 .6 %和 49.7%。病人发生YMDD变异后 ,HBVDNA轻度增高 ,中位值为 1 0 pg/ml;
Objective To evaluate the long term efficacy and safety of lamivudine for chronic hepatitis B and the clinical influence of emergence of YMDD motif mutation of HBV. Methods This multicenter, double blind, randomized, controlled trial began in 1996. A total of 429 patients who were HBsAg, HBeAg and HBV DNA positive were enrolled. They were randomised to receive either lamivudine 100mg daily ( n =322) or placebo ( n =107) for the first 12 weeks. Thereafter all patients were offered open label lamivudine treatment and assessed every 4 weeks for a total of 104 weeks. Results After 12 weeks, 92.2% of the lamivudine recipients had undetectable serum HBV DNA(1.6pg/ml), compared with 14.1% of those in the placebo group ( P <0.01) by Abbott hybridisation method. By week 52,71.0% of the lamivudine group had a sustained serum HBV DNA response, compared with 77.7% of the placebo/lamivudine group. At the end of 2 years, HBV DNA remained below undetected level (<1.6pg/ml), except in patients with the emergence of YMDD mutation whose mean HBV DNA levels increased to 10pg/ml but were much more lower than that of pre treatment baseline level. Lamivudine therapy resulted in increased HBeAg loss and HBeAg/anti HBe seroconversion, which were correlated with both baseline ALT levels and also with duration of lamivudine treatment. HBeAg loss was achieved 26.8% of patients with ALT>1×ULN at 2 years, and in 35.6% and 55.6% of patients with ALT>2×ULN and 5×ULN respectively. For HBeAg seroconversion, these figures were 17.4%, 22.2% and 33.3% respectively. By the end of 2 years, ALT levels were remained in normal ranges in 50.3% whose ALT were abnomal before treatment, and 83% whose ALT were normal before treatment. HBV YMDD mutation were developed in 14.6% and 49.7% patients in 52 weeks and 104 weeks. The mean HBV DNA levels were slightly increased to 10pg/ml and 15% of the patients ALT levels were exceeded baseline. 4 patients were clinically flared up needed to stop treatment. The adverse drug reactions(ADR) of lamivud
出处
《肝脏》
2000年第3期150-154,共5页
Chinese Hepatology
