恩替卡韦和拉米夫定治疗HBeAg阳性的慢性乙型肝炎疗效的荟萃分析

发布时间：2018-07-06 18:19

本文选题：拉米夫定 + 恩替卡韦　；参考：《华中科技大学》2013年硕士论文

【摘要】：目的：通过荟萃分析的方法对比分析恩替卡韦和拉米夫定治疗HBeAg阳性的慢性乙型肝炎患者的疗效及安全性。方法：以慢性乙型肝炎、拉米夫定、恩替卡韦、随机对照、Entecavir(ETV)、lamivudine (LAM)、 Randomized controlled trial（sRCT）、HBeAg-positive chronichepatitis B为检索词，检索2005年1月到2012年6月PubMed、 MEDLINE、EMBASE、中国生物医学文献数据库（CBMdisk）、中国期刊网全文数据库（CNKI）、万方数据库、维普中文科技期刊数据库中关于拉米夫定和恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者的疗效和安全性的随机对照实验（RCT），数据用Review Manager Software5.0进行分析，用相关风险系数（RR）作为效应测量方法，并报告95%置信区间（CI）。Meta分析选用固定效应模型或者随机效应模型，根据Cochran’s异质性Q检验χ2和I2显示是否有异质性，无异质性时选择固定效应模型，有异质性时选择随机效应模型。由两名评价者对检索到的资料独立进行资料提取和方法学质量评价并交叉核对。本研究以丙氨酸氨基转移酶（ALT）复常率、HBV DNA阴转率、HBeAg阴转率、HBeAg血清转换率、耐药性发生率及不良反应为主要评价指标。为减小各试验间异质性，我们选用亚组分析。结果：共纳入7个随机对照试验，，HBeAg阳性慢性乙型肝炎患者1436人，其中ETV组734人，LAM组702人，在4周、8周、12周、24周、48周、96周各个随访时间，ETV组HBV DNA阴转率高于LAM组，差异有统计学意义（RR5.09,95%CI1.99,13.02, P=0.007; RR3.54,95%CI1.99,6.31, P 0.0001; RR1.84,95%CI1.40,2.41, P 0.0001; RR1.45,95%CI1.24,1.70, P 0.0001; RR1.46,95%CI1.27,1.67, P 0.00001; RR1.36,95%CI1.12,1.64, P=0.002）；在4周、8周、12周、24周、48周各个随访时间，ETV组ALT复常率高于LAM组，差异有统计学意义（RR1.99,95%CI1.20,3.29, P=0.008; RR2.03,95%CI1.44,2.84,P 0.0001; RR1.61,95%CI1.09,2.38, P=0.02; RR1.34,95%CI1.06,1.70, P=0.01; RR1.23,95%CI1.12,1.34, P 0.0001），但是在96周随访时ALT复常率差异无统计学意义；在12周、24周、48周、96周各个随访时间，HBeAg阴转率和HBeAg血清转换率在两组对比的差异无统计学意义；耐药性发生率LAM组高于ETV组，差异有统计学意义（RR0.06,95%CI0.01,0.23, P 0.0001）；不良反应未统一进行荟萃分析，LAM组有两名患者在治疗期间死亡。结论：恩替卡韦较之拉米夫定能够更快速高效地抑制HBeAg阳性的慢性乙型肝炎患者的HBV DNA复制，改善患者肝功能，耐药性发生率低，但两药在HBeAg血清学转换方面无明显差异，恩替卡韦和拉米夫定都有良好的安全性和耐受性。
[Abstract]:Objective: to compare the efficacy and safety of entecavir and lamivudine in the treatment of HBeAg positive chronic hepatitis B patients. Methods: chronic hepatitis B, lamivudine, entecavir (ETV) lamivudine (Lam), Randomized controlled trial (sRCT) were used as the key words. To retrieve PubMede, MEDLINE EMBASE, Chinese Biomedical Literature Database (CBMdisk), CNKI, Wanfang Database from January 2005 to June 2012. A randomized controlled trial (RCT) on the efficacy and safety of lamivudine and entecavir in the treatment of HBeAg-positive patients with chronic hepatitis B was carried out in the Weip Chinese Science and Technology Journal database. The data were analyzed with Review Manager Software 5.0. Correlation risk coefficient (RR) was used as an effect measurement method, and 95% confidence interval (CI) .Meta analysis was conducted using fixed effect model or random effect model. According to Q test of Cochrans heterogeneity, 蠂 2 and I 2 showed heterogeneity. When there is no heterogeneity, the fixed effect model is chosen, and the random effect model is chosen when there is heterogeneity. Data extraction, methodological quality evaluation and cross-check were performed by two reviewers. In this study, the seroconversion rate of HBeAg, the incidence of drug resistance and the adverse reaction of HBV DNA and HBeAg seroconversion were used as the main indexes for the evaluation of alanine aminotransferase (alt) normalization rate and HBV DNA negative conversion rate and HBeAg seroconversion rate. In order to reduce the heterogeneity of each test, we selected subgroup analysis. Results: a total of 1436 patients with HBeAg-positive chronic hepatitis B were enrolled in 7 randomized controlled trials, including 734 patients in ETV group and 702 patients in Lam group. The negative rate of HBV DNA in ETV group was higher than that in Lam group at 4 weeks, 8 weeks, 12 weeks, 48 weeks and 96 weeks, and the negative rate of HBV DNA in ETV group was higher than that in Lam group. The difference was statistically significant (RR5.0995 CI1.99 / 13.02, P0.007; RR3.5495 CI1.99 6.31, P 0.0001; RR1.8495 / 95CI1.402.41, P 0.0001; RR1.4595CI1.241.70, P 0.0001; RR1.4695CI1.271.67, P 0.00001; RR1.36-95CI1.12121.64, P0.002); the rate of recovery of ALT in ETV group was higher than that in Lam group at every follow up time of 24 weeks and 48 weeks. The difference was statistically significant (RR1.99-95CI 1.203.29, P0. 008; RR2.03C1.44, 2.84, P0.0001; RR1.61C95CI1.09C1.092.38, P0.02; RR1.34C95CI1.061.70, P0.01; RR1.23c95CI1.12C1.34, P 0.0001), but there was no significant difference in the recovery rate of alt at 96 weeks. There was no significant difference in HBeAg negative conversion rate and HBeAg seroconversion rate between the two groups at 12 weeks and 24 weeks and 48 weeks and 96 weeks, but the incidence of drug resistance in Lam group was higher than that in ETV group (RR0.06 / 95 CI 0.01 卤0.23, P 0.0001). Adverse reactions were not uniformly meta-analyzed. Two patients in the lam group died during treatment. Conclusion: compared with lamivudine, entecavir can inhibit HBV DNA replication in HBeAg-positive patients with chronic hepatitis B more quickly and efficiently, improve liver function and lower incidence of drug resistance, but there is no significant difference between the two drugs in HBeAg serological conversion. Both entecavir and lamivudine have good safety and tolerance.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R512.62

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