恩替卡韦联用阿德福韦酯治疗拉米夫定耐药的慢性乙型肝炎的系统评价

Systematic review on entecavir combined with adefovir dipivoxil for the treatment of lamivudine-resistant chronic hepatitis B(CHB

目的:系统评价恩替卡韦联用阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎的疗效和安全性。方法:计算机检索Pub Med、Medline、CNKI、CBM、VIP和万方数据库,同时手工检索相关文献,收集恩替卡韦联用阿德福韦酯与拉米夫定联用阿德福韦酯的随机对照研究,检索年限均为建库至2016年3月。由2名研究者独立按照纳入与排除标准筛选文献、提取资料和纳入研究进行文献质量评价,应用Rev Man5.2软件进行统计分析。结果:共纳入8项研究,合计840例患者。Meta分析结果显示,对于拉米夫定耐药的CHB者,恩替卡韦联用阿德福韦酯与拉米夫定联用阿德福韦酯的血清HBV-DNA转阴率(RR=1.23,95%CI:1.14~1.32),P<0.01)、ALT复常率(RR=1.30,95%CI:1.16~1.45,P<0.01)和耐药基因变异率(RR=0.11,95%CI:0.03~0.48,P<0.01)差异均存在统计学意义,HBe Ag阳性转阴率(RR=1.09,95%CI:0.92~1.30,P>0.05)和ADR发生率(RR=0.81,95%CI:0.39~1.68,P>0.05)差异性均无统计学意义。结论:现有证据表明,恩替卡韦联用阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎优于拉米夫定联用阿德福韦酯。受纳入研究质量限制,上述结论尚需进一步大样本量、高质量随机对照研究验证。

Objective： To systematic review the efficacy and safety of entecavir combined with adefovir dipivoxil for the treatment of lamivudine-resistant chronic hepatitis B. Methods： Retrieved from PubMed, Medline, CNKI, VIP, Wanfang database online version from the time of database creation to March 2016, meanwhile related articles were searched by manual retrieval, and the reference lists of enrolled reports and reviews were looked up. Randomized controlled study compared entecavir combined with adefovir dipivoxil for the treatment of lamivudine resistant chronic hepatitis B with lamivudine combined with adefovir dipivoxil as control groups. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and assessed the methodological quality of includes studies. Meta-analysis of included trials was performed using Rev Man 5.2 software. Results： A total of 8 studies were included, involving 840 patients. Meta-analysis showed that, for lamivudine resistant CHB patients, there were significantly difference between the entecavir combined with adefovir dipivoxil and lamivudine combined with adefovir dipivoxil in the negative rates of serum HBV-DNA （RR=l.23, 95% CI：1.14-1.32, P〈0.01）, serum ALT recovery rate （RR=I.30, 95% C/：1.16-1.45, P〈0.01） and drug resistance gene mutation rate （RR=0.11, 95% C1：0.03-0.48, P〈0.01）. There were no significantly differences in negative rates of serum HBeAg （RR=I.09, 95% CI： 0.92-1.30, P〉0.05） and rate ofADR （RR=0.81, 95% CI：0.39-1.68, P〉0.05）. Conclusion： Current evidence shows entecavir combined with adefovir dipivoxil in the treatment of lamivudine resistant chronic hepatitis B is superior to lamivudine combined with adefovir dipivoxil. Given the low quality of the included literature research, accurate results still need a large sample, high-quality randomized controlled study further verification.