拉米夫定治疗HBeAg阳性慢性乙型肝炎随机对照试验的Meta分析

目的评价拉米夫定治疗HBeAg阳性慢性乙型肝炎的疗效。方法检索MEDLINE,SCI,CurrentContent Connect,Cochrane图书馆和CBMdisc,并追查所有纳入研究的参考文献。检索年限均从建库检索到2005年9月。纳入拉米夫定与安慰剂、空白或支持治疗比较治疗HBeAg阳性慢性乙型肝炎的随机对照试验(RCT)。由两名评价员独立筛查文献,评价质量和提取资料。采用χ2检验鉴定研究间异质性,使用随机效应和固定效应模型合并研究,对疗程进行亚组分析。结果纳入11个RCT(n=1333),研究拉米夫定100mg/d的疗效,其中1个RCT同时研究拉米夫定25mg/d。8个RCT拉米夫定的疗程为常规疗程(52周);3个RCT为短疗程(≤26周),其中2个为12周、1个为26周。纳入文献的总体质量较高,6个研究采用了正确的随机分配方法,4个分配隐藏较充分,5个较好地实施了盲法;其余5个仅简单叙述为随机试验,未描述随机产生的方法;1个研究的盲法实施不充分。3个研究未报道失访人数及原因,其余均作了详细描述且采用意向性分析。纳入研究的随机方法、分配隐藏及盲法实施均无部分充分者。Meta分析结果显示,拉米夫定(100mg/d)常规疗程(52周)HBeAg转阴率高于对照组41·2%vs12·9%,RR=3·20,95%CI(2·33,4·39)],HBV-DNA转阴率高于对照组70·2%vs20·1%,RR=3·40,95%CI(2·77,4·16)],HBeAg血清转换率高于对照组15·3%vs7·03%,RR=2·13,95%CI(1·22,3·49)],组织学反应率高于对照组57·9%vs26·2%,RR=2·17,95%CI(1·67,2·81)],ALT复常率高于对照组65%vs34·9%,RR=1·91,95%CI(1·64,2·21)]。短疗程者仅HBV-DNA转阴率拉米夫定组高于对照组50·7%vs3·9%,RR=8·68,95%CI(1·72,43·74)],其差异有统计学意义。但HBeAg转阴、HBeAg血清转换及ALT复常,拉米夫定组均与对照组无统计学差异。拉米夫定25mg/d的HBV-DNA转阴率高于对照组97·9%vs22·2%,RR=4·41,95%CI(2·86,6·79)];组织学反应率高于对照组59·3%vs30%,RR=1·98,95%CI(1·31,2·99)],但HBeAg血清转换与对照组相比,差异无统计学意义。结论拉米夫定100mg/d,52周可使HBeAg阳性的慢性乙肝患者的HBV-DNA转阴、HBeAg转阴、ALT复常及HBeAg血清转换。

Lamivudine for HBeAg Positive Chronic Hepatitis B: A Meta-analysis of Randomized Controlled Trials

Objective To assess the efficacy of lamivudine in patients with HBeAg positive chronic hepatitis B. Methods MEDLINE, SCI, Current Content Connect, The Cochrane Library, and Chinese Biomedical Database were searched from the beginning to September 2005, and the references of eligible studies were manually screened. Randomized controlled trials comparing lamivudine with non-antiviral interventions (placebo, no treatment and standard care) in patients with chronic hepatitis B were eligible for inclusion. Two investigators independently assessed the quality and extracted the data. Heterogeneity was examined by Chi-square test. Fixed and random effect meta-analysis were used to pool the data. Subgroup analyses were used in treatment course. Results Eleven RCTs were included (n= 1 237 ). All reported the effect of lamivudine (100 mg/d), and one of them included lamivudine (25 mg/d). The treatment duration of 52 weeks and less than 26 weeks were reported in eight and three RCTs, respectively. Six RCTs adequately applied randomization, while other five RCTs were not reported in detail. Four RCTs adequately enforced allocation concealment, five RCTs enforced blinding bitterly. The others were not reported in detail. It was found by meta-analysis that, compared with the control, lamivudine (100 mg/d, 52 W) could significantly clear HBeAg 42.6% vs. 13% , RR 3.20, 95%CI (2.33,4.38)] and clear HBV DNA 71.78% vs. 20.36%, RR 3.42, 95%CI (2.80,4.19)], normalize ALT 65% vs. 34.9%, RR 1.91, 95%CI (1.64,2.21)], achieve HBeAg seroconversion 16.1% vs. 7.29%, RR 2.12, 95%CI (1.24,3.80)] and histology response 57.9% vs. 26.2%, RR 2.17, 95%CI (1.67,2.81)]; Lamivudine (100 mg/d,12 W) could effectively clear HBV DNA 50.7% vs 3.92%, RR 8.68, 95%CI (1.72,43.74)], but was not effective in loss of HBeAg, HBeAg seroconversion and normalization of ALT. Lamivudine (25 mg/d) could effectively clear HBV DNA 97.7% vs. 22.2%, RR 4.41, 95%CI (2.86,6.79)] and improve histology response 59.3% vs. 30%, RR1.98, 95%CI (1.31,2.99)], but was not effective in HBeAg seroconversion. Conclusions Lamivudine (100 mg/d) is effective in clearing HBV DNA and HBeAg, normalizing ALT and achieving HBeAg seroconversion.