阿德福韦酯联合拉米夫定治疗拉米夫定耐药慢性乙型肝炎患者随机对照试验的Meta分析

Adefoveir dipivoxil in combination with lamivudine on treatment of lamivudine-resistant patients with hepatits B:meta analysis

目的评价阿德福韦酯(ADV)联合拉米夫定(LAM)治疗对拉米夫定耐药的慢性乙型肝炎患者的疗效及安全性。方法纳入阿德福韦酯联合拉米夫定治疗拉米夫定耐药的慢性乙型肝炎患者的随机对照试验(RCT)研究结果,对照组均为ADV单药治疗。由两名评价员独立筛查文献,进行质量评价和资料提取。使用Cochrance协作网提供的RevMan5.0软件进行Meta分析。结果 Meta分析结果显示,经过48周或48个月治疗,治疗组丙氨酸氨基转移酶(ALT)复常率均优于对照组,其OR(95%CI,P)分别为1.84(1.12～3.00,0.02)和80.29(4.18～1541.64,0.004);治疗组HBVDNA低于检测下限的比率优于对照组,RR(95%CI,P)分别为1.22(1.06～1.39,0.004)或1.90(1.10～3.30,0.02);两组HBeAg转阴率无显著性差异,OR(95%CI,P)为1.02(0.40～2.58,0.97);HBeAg血清学转换率无统计学差异,RR(95%CI,P)为1.30(0.63～2.68,0.47)。ADV相关耐药发生率,治疗组显著低于对照组,OR(95%CI,P)分别为0.13(0.03～0.58,0.008)和0.07(0.01～0.40,0.003)。结论与ADV单用治疗方案相比,ADV联合LAM治疗LAM耐药的慢性乙型肝炎患者,能显著提高ALT复常率、HBVDNA低于检测下限的比率,降低ADV相关耐药发生率;HBeAg阴转率或HBeAg血清学转换率相似。ADV10mg/d长期治疗慢性乙型肝炎未出现严重不良事件,相对较为安全。

Objective To evaluate the efficacy and safety of combination therapy of lamivudine（LAM） and adefoveir dipivoxil（ADV） compared with ADV monotheray for LAM-resistant patients with chronic hepatitis B（CHB）.Methods RCTs studies of combination therapy of ADV and LAM for LAM-resistant patients with CHB were searched,in which the control group was ADV monotheray.Two reviewer assessed the documents＇ quality separately and completed data extraction.The statistical analysis was dealed with Revman 5.0 software.Results After treatment for 48 weeks or 48 months,the biochemical response ratio in ADV ＋ LAM combination group was higher than that in ADV monotherapy group,with OR（95%CI,P）：1.84（1.12-3.00,0.02） and 80.29（4.18-1541.64,0.004）,respectively;higher virological response rates were observed in ADV ＋ LAM combination group compared with ADV monotherapy group,and the difference in response rate between two groups were statistically significant,with RR（95%CI,P）：1.22（1.06-1.39,0.004） and 1.90（1.10-3.30,0.02）,respectively;the ratios of HBeAg clearance and HBeAg seroconversion between two groups were similar,with OR（95%CI,P） in ADV monotherapy and ADV＋LAM combination therapy 1.02（0.40-2.5,0.97） and 1.30（0.63-2.68,0.47）,respectively.Greater emergence ratio of ADV-resistant mutants（95%CI,P） were observed：0.13（0.03-0.58,0.008） and 0.07（0.01-0.40,0.003）.Conclusions Current studies on LAM-resisant patients with CHB indicated that combination therepy of ADV and LAM was superior on HBV replication inhibition,biochemical response and ADV drug resistance prevention compared with LAM monotherapy;effects on HBeAg clearance and seroconversion between combination therapy and monotherapy were similar.Long-term application of ADV with 10 mg/d was generally well tolerated,and no patient had to cease therapy because of renal toxicity.