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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;4
Objectives To evaluate the long-term efficacy and safety of lamivudine in the treatment of chronic hepatitis B and its clinical impact on the development of viral mutations during treatment. The method is a multicenter, double-blind, randomized, placebo-controlled clinical trial. 429 cases of HBsAg and HBeAg-positive chronic hepatitis B, were randomly divided into lamivudine treatment group and control group according to 3: 1, lamivudine were taken 100 mg / d and placebo for 12 weeks, then all Patients were taking lamivudine, were observed for 2 years. Results After 12 weeks of treatment, the cumulative HBVDNA negative conversion rate (<1.6pg / ml) in the lamivudine group was 92.2% and in the placebo group was only 1.4.1% (P <0.01). At week 52, the negative conversion rates in the lamivudine and placebo / lamivudine groups were 71.0% and 77.7%, respectively (P> 0.05). At the end of the second year, the mean of HBVDNA continued to be below the minimum measured value, except for patients who had a YMDD mutation. After lamivudine treatment, some patients had HBeAg negative and HBeAg (-) / anti-HBe (+) seroconversion, the occurrence of which was related to the level of ALT and the course of treatment before treatment. Serum ALT> 1ULN (upper limit of normal),> 2ULN and> 5ULN patients were 26.8%, 35.6% and 55.6% respectively at the end of the second year of treatment; the seroconversion rates were 1 1.4%, 22.2% and 33.3% respectively. Pretreatment ALT increased in 202 cases, 50.3% after 2 years to maintain normal; normal ALT 224 cases, 83% ALT is still normal. The incidence of YMDD mutations at the first year and the second year were 14.6% and 49.7%, respectively. After the occurrence of YMDD mutation in patients, HBVDNA slightly increased, the median was 10 pg / ml; 4