拉米夫定和阿德福韦酯初始联合治疗慢性乙型肝炎的临床研究:阿德福韦酯和拉米夫定

　　[摘要] 目的 观察拉米夫定（LAM）和阿德福韦酯（ADV）初始联合治疗与恩替卡韦（ETV）单药治疗慢性乙型肝炎的疗效。 方法 选择我院2008年7月～2010年6月符合抗病毒治疗的未曾使用过核苷（酸）类似物的初治慢性乙型肝炎患者334例，分为联合组192例，单药组142例，联合组应用LAM 100 mg，ADV 10 mg，每日1次，单药组应用ETV 0.5 mg，每日1次。分别在基线，12、24、36、48、72、96周时留取血清，采用化学发光法定量检测HBsAg和HBeAg，采用实时荧光定量聚合酶链反应（PCR）检测HBV DNA水平，采用PCR产物直接测序法检测病毒耐药基因。 结果 ①两组在治疗12周和24、36、48周时时，HBV DNA＜500拷贝/mL的比率，差异无统计学意义（P ＞ 0.05）。②治疗72周和96周时，HBV DNA＜500拷贝/mL的比率，联合组分别为77%、78%，单药组分别为77%、76%，两组比较差异有统计学意义（均P ＜ 0.05）。③治疗96周时，联合组未见病毒学突破和耐药发生，而单药组检测到1例恩替卡韦相关耐药基因变异位点。 结论 LAM和ADV初始联合治疗，在减少病毒学突破和耐药发生及长期疗效发面优于ETV单药治疗。
　　[关键词] 拉米夫定；阿德福韦酯；恩替卡韦；慢性乙型肝炎
　　[中图分类号] R575.2 [文献标识码] A [文章编号] 1673-7210（2012）07（c）-0085-02
　　Clinical research of Lamivudine and Adefovir Dipivoxil initial combination therapy for chronic hepatitis B
　　LI Fang1 LEI Feifei1 LI Gang1 GONG Zuojiong2 TAN Huabing1
　　1.Department of Infection, the People"s Hospital Affiliated to Hubei University of Chinese Medicine, Hubei Province, Shiyan 442000, China; 2.Department of Infection, the People"s Hospital of Wuhan University, Hubei Province, Wuhan 430060, China
　　[Abstract] Objective To compare the efficacy of Lamivudine (LAM) plus Adefovir Dipivoxil (ADV) com bination therapy and Entecavir (ETV) monotherapy for chronic hepatitis B patients. Methods 334 patients with chronic hepatits B managed in a single-center clinical practice (median 96 weeks) were split into 2 cohorts, one was treated with de-novo combination Lamivudine plus Adefovir (10 mg/d) (LAM+ADV), the other with ETV (0.5 mg/d) monotherapy. Serum levels of ALT, HBsAg, HBeAg and HBV viral load, together with genotypic resistence were analyzed at 0, 12, 24, 36, 48, 72, 96 weeks, respectively. HBV DNA was determined by real-time PCR. HBsAg and HBeAg were assessed by chemiluminescence. Serum levels of ALT was detected by automatic biochemical analyzer. HBV genotypic resistence was tested by direct sequencing. Results ①The rate of HBV DNA ＜ 500 copies/mL had no significant difference between LAM+ADV and ETV cohorts by the 12, 24, 36, 48 weeks (P ＞ 0.05). ②At the time of 72 and 96 week, the rate of HBV DNA ＜ 500 copies/mL were markedly higher in combination therapy cohort than those of monotherapy cohort statistically (all P ＜ 0.05). ③No virological breakthrough occurred in combination therapy cohorts at the end of treatment. One patient in monotherapy cwhort was confirmed to be of variants associated with ETV resistance. Conclusion Present study suggests that LAM plus ADV denovo combination therapy was more efficacious than ETV monotherapy for chronic hepatitis B patients