拉米夫定和阿德福韦酯初始联合与恩替卡韦单药治疗慢性乙型肝炎的疗效和安全性比较  

Efficacy and safety of lamivudine plus adefovir combination therapy and entecavir monotherapy for chronic hepatitis B patients

作　　者：喻剑华[1] 施军平[1] 武静[1] 李晓鸥[1] 过建春[1] 荀运浩[1] 赵春[1] 金洁[1] 徐爱芳[1] 娄国强[1] 

机构地区：[1]浙江中医药大学附属杭州市第六医院,310014

出　　处：《中华肝脏病杂志》2011年第2期88-92,共5页Chinese Journal of Hepatology

基　　金：基金项目：杭州市科技计划项目（20090833819）;中国肝炎防治基金会“光辉”基金项目（GHF2010211）

摘　　要：目的观察拉米夫定（LAM）和阿德福韦酯（ADV）初始联合与恩替卡韦（ETV）单药治疗慢性乙型肝炎的疗效，并比较两者的安全性。方法选择我院2007年6月2008年1月符合抗病毒治疗的未曾使用核苷（酸）类似物的初治慢性乙型肝炎患者120例，分为联合组60例和单药组60例，联合组应用LAM100mg，ADV10mg，每日1次；单药组应用ETV0．5mg，每日1次。分别在基线、12、24、48、96周时留取血清，采用全自动分析生物化学仪检测肝功能、肾功能、血生物化学指标；采用化学发光法定量检测HBsAg和HBeAg；采用实时荧光定量PCR检测HBVDNA水平；采用PCR产物直接测序法检测病毒耐药基因。组间比较采用配对t检验，率的比较采用χ^2检验。结果（1）联合组54例，单药组50例完成了48周随访，联合组51例，单药组48例完成了96周随访。两组治疗前性别、年龄、血清ALT、血肌酐、HBVDNA、HBsAg水平及HBeAg阳性率，差异无统计学意义，具有可比性。（2）两组在治疗12周和24周时，HBVDNA〈300拷贝／ml和HBVDNA〈1000拷贝／ml的比率，差异无统计学意义。治疗12周时，单药组和联合组HBVDNA下降〈1log10拷贝／ml的分别为3．7％（2／54）和18．0％（9／50），两组比较，χ^2=5．556，P〈0．05，差异有统计学意义。（3）治疗48周时，单药组和联合组的ALT复常率、HBVDNA〈1000拷贝／ml的比率、HBeAg血清转换率以及与基线比较HBVDNA下降绝对值，差异均无统计学意义。联合组与单药组HBVDNA〈300拷贝／ml的患者分别为90．7％（49／54）和76．0％（38／50），两组比较，χ^2=4．125，P〈0．05，差异有统计学意义。（4）治疗96周时，HBVDNA〈300拷贝／ml、HBVDNA〈1000拷贝／ml患者比率和HBeAg血清转换率，联合组分别为96．1％（49／51）、98．0％（50／51）、41．7％（15／36），单药组分别为79．2％（38／48）、87．5％（42／48）、16Objective To compare the efficacy and safety of Lamivudine （LAM） plus Adefovir dipivoxil （ADV） combination therapy and Entecavir（ETV） monotherapy for chronic hepatitis B patients. Methods 120 patients with chronic hepatitis B managed in a single-centre clinical practice （median 96 weeks）were split into 2 cohorts, one was treated with de-novo combination Lamivudine （100 mg/day） plus Adefovir （10 mg/day） （LAM＋ADV）, the other with Entecavir （0.5 mg/day） monotherapy. Serum levels of ALT, creatinine, HBsAg, HBeAg and HBV viral load, together with genotypic resistence were analyzed at 0, 12, 24, 48, 96 weeks, respectively. HBV DNA was determined by real-time PCR＋ HBsAg and HBeAg were assessed by chemiluminescence. Serum levels of ALT and creatinine were detected by automatic biochemical analyzer. HBV genotypic resistence was tested by direct sequencing. Results （1） At the time point of 96 weeks, a total of 99 patients（51 cases in combination therapy cohort and 48 case in monotherapy cohort） were compared. The baseline characteristics as for HBV viral load, median age, serum levels of ALT and creatinine were compatible between combination therapy cohort and monotherapy cohort. （2） The rates of HBV DNA 〈 300 copies/ml and HBV DNA 〈 1000 copies/ml had no significant difference between LAM ＋ ADV and ETV cohorts by the 12 and 24 weeks （P 〉 0.05）. （3） At the time point of 48 weeks, the rates of HBV DNA〈1000 copies/ml, HBeAg seroconversion, and ALT normalization were similar in both cohorts, though the rate of HBV DNA 〈 300 copies/ml was obviously higher in combination therapy cohort than that of monotherapy cohort （90.7% vs 76%, P 〈 0.05）. （4） At the time point of 96 weeks, the rates of HBV DNA 〈 300 copies/ml （96.1% vs 79.2%）, HBV DNA 〈 1000 copies/ml （98% vs 87.5%） and the HBeAg seroconversion （41.7% vs 16.7%） were markedly higher in combination therapy cohort than those of monotherapy cohort statistically （P 〈 0.05 for all）

关 键 词：肝炎 乙型 慢性 拉米夫定 治疗 阿德福韦酯 恩替卡韦 耐药 

分 类 号：R512.62[医药卫生—内科学]