阿德福韦酯、恩替卡韦治疗HBV-M204I/V变异的慢性乙肝疗效观察

目的探讨阿德福韦酯、恩替卡韦治疗HBV-M204I/V变异的慢性乙肝患者的疗效及安全性。方法采用阿德福韦酯、拉米夫定治疗127例HBV-M204I/V阳性的慢性肝病患者24周,其中32例HBV-DNA阳性患者改用阿德福韦酯、恩替卡韦治疗（观察组）,95例继用原治疗方案（对照组）。治疗36、48、72、96、120、144周时检测两组血清ALT、HBV-DNA、乙肝血清学标志物及HBV变异,观察药物不良反应。结果治疗36、48、72周时,对照组、观察组血清HBV-DNA转阴者分别为77、82、84例,31、32、32例;ALT复常者分别为78、80、84例,32、32、32例,两组比较均有统计学差异（P均〈0.05）。96、120、144周时,两组血清HBV-DNA及ALT比较无统计学差异。结论恩替卡韦、阿德福韦酯治疗HBV-M204I/V变异的慢性乙肝的疗效优于拉米夫定、阿德福韦酯联用者。     

恩替卡韦或其联合阿德福韦酯补救治疗拉米夫定联合阿德福韦酯应答不佳的慢性乙型肝炎

目的 对拉米夫定(LAM)初治耐药后,LAM联合阿德福韦酯(ADV)应答不佳的慢性乙型肝炎患者,分别采用恩替卡韦(ETV)单药或ETV联合ADV进行补救治疗,比较两种补救方案的疗效.方法 对LAM初治耐药后应用LAM联合ADV应答不佳的40例患者,分别应用ETV 1.0 mg/d(14例)及ETV 0.5 mg/d联合ADV 10mg/d (26例)两种方案进行补救治疗,至少观察48周,定期监测HBV DNA、肝肾功能、HBV标志物等指标.根据资料不同分别采用t检验Wilcoxon检验或x2检验.结果 两组患者采用补救治疗前的基线情况差异无统计学意义.分别采用两种补救方案治疗后,两组患者HBV DNA水平均有下降,但ETV联合ADV组下降幅度较大.补救治疗24周时,ETV 1,0mg组有28.6％％(4例)达到HBV DNA转阴,ETV联合ADV组则有80.8％ (21例)达到HBV DNA转阴,x2=8.469,P=0.004,差异具有统计学意义;48周时,ETV1.0mg组仍仅有4例患者HBV DNA转阴,而ETV联合ADV组全部26例患者均达到HBV DNA转阴.补救治疗24周时,ETV 1.0mg组有42.9％(6例)患者ALT复常,ETV联合ADV组有92.3％ (24例)患者ALT复常,x 2=9.337,P=0.002,差异具有统计学意义;48周时,ETV 1.0mg组有57.1％(8例)患者ALT复常,而ETV联合ADV组所有患者均达到ALT复常.补救治疗48周时,ETV 1.0mg组有1例患者发生HBeAg血清学转换,ETV联合ADV组有4例患者发生HBeAg血清学转换.结论 对于LAM耐药后LAM联合ADV应答不佳的慢性乙型肝炎患者,采用ETV联合ADV的补救方案较ETV单药1.0mg的方案更为有效,可以实现更好的病毒学及生物化学应答.     

恩替卡韦和阿德福韦酯分别治疗HBeAg阳性慢性乙型肝炎近期疗效分析

目的探讨ETV、ADV分别治疗初治慢性乙肝的疗效,探索其最佳适应证。方法 143例初治慢性乙肝患者分为两组,其中ETV组68例,ADV组75例,ETV组口服ETV0.5mg,每晚10时空腹服;ADV组口服ADV10mg,每日一次,均连用48W。结果治疗至48W时,HBVDNA高度应答率、HBeAg阴转率、ALT复常率ETV组分别为：79.4%、29.4%、85.3%,ADV组分别为：37.3%、20.0%、86.7%;HBVDNA高度应答率ETV组高于ADV组,两组比较差异有统计学意义（P〈0.01）。随着治疗前HBVDNA载量的升高,治疗至48W时,HBVDNA的高度应答率呈递减趋势;在同一HBVDNA载量下,ETV组的高度应答率均高于ADV组,且两组比较差异有统计学意义。结论 ETV更适用于HBVDNA高载量尤其是HBVDNA≥10^7拷贝/ml者,对于由HBV复制所致的重型肝炎及有重型肝炎倾向者则首选本品;ADV更适合于HBVDNA中、低载量,尤其是HBVDNA（10^5～10^6）拷贝/ml者,对于失代偿期肝硬化则作为首选。     

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

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、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HBV DNA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χ2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、HBV DNA、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,HBV DNA＜300拷贝/ml和HBV DNA＜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HBV DNA下降＜1 log10拷贝/ml的分别为3.7%(2/54)和18.0%(9/50),两组比较,χ2=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HBV DNA下降绝对值,差异均无统计学意义.联合组与单药组HBV DNA＜300拷贝/ml的患者分别为90.7%(49/54)和76.0%(38/50),两组比较,χ2=4.125,P＜0.05,差异有统计学意义.(4)治疗96周时,HBV DNA＜300拷贝/ml、HBV DNA＜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)、16.7%(6/36),两组比较,χ2值分别为6.639、4.180、5.445,P值均＜0.05,差异有统计学意义;但两组患者与基线比较HBV DNA和HBsAg下降绝对值以及ALT复常率差异无统计学意义.(5)治疗96周时,联合组未见病毒学突破和耐药发生,而单药组累计发生病毒学突破4例,其中3例(6.3%,3/48)检测到ETV相关耐药基因变异位点,2例患者在基线时存在LAM相关耐药基因变异位点(rtL180M+M204V).(6)治疗48、96周时,联合组与单药组患者血肌酐水平及治疗前后血肌酐升高水平差异无统计学意义.在治疗期间,两组均无血清肌酐水平超过正常上限或由于肌酐升高0.5 mg/dl而调整剂量的患者.结论 LAM和ADV初始联合治疗,在减少病毒学突破和耐药发生,以及提高HBeAg血清转换率方面优于ETV单药治疗.

Abstract：

Objective 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),thc 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＜1000copies/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).The mean values of decreases for HBV viral loads and HBsAg levels were smilar in both cohorts at 48 and 96 weeks.(5) Elevated serum creatinine not be found in both cohorts at the end of treatment.(6) No virological breakthrough occurred in combination therapy cohort at the end of treatment.Four patients in monotherapy cohort were found with virological breakthrough at 96 weeks and three cases among were confirmed to be of variants associated with ETV resistance (rtLl80M + T184L + M204V).Conclusions Present study suggests that Lamivudine plus Adefovir dipivoxil de-novo combination therapy was more efficacious than Entecavir monotherapy for CHB patients and the tolerance is compatible.     

阿德福韦酯和恩替卡韦的疗效比较

已有大量研究数据表明核苷(酸)类似物抗HBV的效果良好,并被推荐使用~([1]).但随着临床应用病例数的增多,如何使初治患者尽可能避免或减少因长期应用所致的耐药性已成为临床医师需要积极面对的问题.     

阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎的临床研究

目的研究阿德福韦酯片对拉米夫定耐药慢性乙型肝炎患者的疗效和安全性。方法采用多中心、随机，双盲双模拟、拉米夫定对照的临床试验，选择拉米夫定耐药的HBeAg阳性慢性乙型肝炎患者209例，按1：1的比例随机分为阿德福韦酯组105例，拉米夫定组104例。完成24周和48周治疗时，检测血清HBV DNA水平、乙型肝炎病毒血清学标志物及肝功能变化。结果治疗24周时阿德福韦酯组血清HBV DNA水平，平均下降2．40log10，病毒应答率为59．0％，丙氨酸氨基转移酶（ALT）复常率为54．3％，均显著高于拉米夫定组；治疗48周时阿德福韦酯组血清HBV DNA水平，平均下降2．71log10病毒应答率为61．9％，ALT复常率为54．3％，显著优于拉米夫定组；阿德福韦酯组治疗后血清HBeAg阴转率、HBeAg血清转换率及不良事件发生率与拉米夫定组相比，差异无统计学意义。未发生与研究药物相关的严重不良反应。结论阿德福韦酯片治疗拉米夫定耐药慢性乙型肝炎，可在病毒学及生物化学方面取得较好疗效，且安全性良好。     

恩替卡韦与阿德福韦酯治疗对慢性乙型肝炎患者生存质量的影响

本研究旨在借助于简明的生存质量量表(SF-36中文版)探讨恩替卡韦(ETV)与阿德福韦酯(ADV)治疗慢性乙型肝炎患者48周后对患者生存质量的影响及其相关影响因素.一、资料与方法1.研究对象:选择2007年4月-2008年7月于济南市传染病医院就诊的120例慢性乙型肝炎患者,诊断均符合2005年<慢性乙型肝炎防治指南>的诊断标准.2.治疗方法:将120例慢性乙型肝炎患者按1∶1比例随机分为ETV组(0.5 mg/d)与ADV组(10 mg/d).如因应答不佳或耐药变异需要调整治疗者均记录.     

恩替卡韦联合阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎患者的疗效观察

目的观察恩替卡韦联合阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎(CHB)患者的疗效和安全性。方法选取昆山市人民医院2011年5月至2013年5月门诊和住院的拉米夫定耐药患者45例,随机分成两组,治疗组23例应用恩替卡韦联合阿德福韦酯挽救治疗,对照组22例应用拉米夫定联合阿德福韦酯挽救治疗,观察两组治疗前及治疗后4、12、24、48周HBV DNA、ALT、AST、TBil、Alb、HBV血清学标志物含量变化以及治疗48周时非rtM204I位点变异发生率。计量资料组间比较用t检验,计数资料的组间比较用四格表χ2检验。结果治疗组挽救治疗后4、12周ALT、AST下降较对照组相比差异有统计学意义(t值为3.124、5.271、4.476、5.125,P值均0.01),挽救治疗24、48周后较对照组相比差异有统计学意义(t值为2.240、2.307、2.886、2.908,P值均0.05)。治疗4、12、24、48周后,治疗组HBV DNA转阴率分别为73.9%、86.8%、95.7%、100%,较对照组差异有统计学意义(χ2值为11.79、5.75、10.29、5.89,P值均0.05)。HBeAg阳性患者阴转率在治疗组及对照组间差异无统计学意义。治疗组48周后未出现新的非rtM204I位点变异,而对照组非rtM204I位点变异情况为4例,两组相比差异有统计学意义(χ2=4.59,P0.05)。结论恩替卡韦联合阿德福韦酯用于既往拉米夫定耐药的CHB患者的挽救治疗疗效明显,值得临床推广。     

拉米夫定联合阿德福韦酯治疗与恩替卡韦单药治疗HBeAg阳性慢性乙型肝炎患者48周疗效比较

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HBeAg阳性慢性乙型肝炎（CHB）患者的疗效、耐药率及安全性。方法选择2008年5月-2010年2月佛山市第一人民医院HBeAg阳性CHB患者56例,采用随机数字表法分为联合治疗组和单药治疗组,联合治疗组服用LAM（100 mg/d）和ADV（10 mg/d）,1次/d,疗程为48周;单药组服用ETV（0.5 mg/d）,1次/d,疗程48周。两组患者基线情况比较采用t检验,两组的ALT复常率、HBV DNA阴转率和HBeAg转阴率采用χ2检验进行比较。结果治疗48周时ALT复常率在联合治疗组与单药治疗组间差异无统计学意义（χ2=1.018,P〉0.05）,但治疗36周时单药组ALT复常率高于联合治疗组,差异有统计学意义（χ2=4.082,P〈0.05）。治疗12和48周时,两组间的HBV DNA转阴率差异无统计学意义（χ2=1.167、1.976,P〉0.05）,治疗24和36周,单药治疗组HBV DNA转阴率高于联合治疗组,差异有统计学意义（χ2=5.600、9.164,P〈0.05）。两组间的HBeAg转阴率差异无统计学意义（P〉0.05）。治疗过程中,两组均未出现耐药,安全性良好。结论治疗48周时,LAM与ADV初始联合或ETV单药治疗HBeAg阳性CHB均具有较好的疗效;ETV单药治疗容易较早出现ALT复常和HBV DNA阴转;两组药物安全性好、耐药率低,疗效显著,值得推广应用。     

阿德福韦酯和恩替卡韦治疗慢性乙型肝炎疗效观察

目的观察阿德福韦酯和恩替卡韦治疗HBeAg阳性慢性乙型肝炎的疗效。方法应用阿德福韦酯治疗19例,恩替卡韦治疗18例慢性乙型肝炎患者,观察48周。结果治疗48周时,ADV组HBV DNA转阴率为79%,而ETV组为100%（P〈0.05）;恩替卡韦治疗患者ALT复常率也显著高于阿德福韦酯治疗组;两组HBeAg阴转和需要停药的不良事件发生情况无显著相差。结论阿德福韦酯和恩替卡韦均有较好的治疗作用,但本研究观察时间尚短。     

恩替卡韦和阿德福韦酯治疗乙型肝炎肝硬化合并肝源性糖尿病患者的效果比较

目的观察乙型肝炎肝硬化合并肝源性糖尿病患者分别应用恩替卡韦及阿德福韦酯抗病毒治疗的临床疗效。方法选取在青岛市传染病医院就诊的乙型肝炎肝硬化并肝源性糖尿病患者80例,根据患者所选抗病毒药物的不同,分为A、B两组,每组各40例。A组患者口服恩替卡韦0.5 mg,1次/d,B组患者口服阿德福韦酯10 mg,1次/d,抗病毒治疗48周。两组患者同时给予糖尿病饮食、胰岛素控制血糖及保肝、降酶等治疗。观察两组患者治疗前后生化学指标、病毒学应答情况、糖尿病控制情况及肝硬度等有无改善。计量资料两组间比较采用t检验。计数资料两组间比较采用χ2检验。结果恩替卡韦组患者病毒学应答率为85%(34/40),阿德福韦酯组患者病毒学应答率为65%(26/40),两组病毒学应答率差异有统计学意义(χ2=4.27,P0.05)。恩替卡韦组患者临床生化特征改善较阿德福韦酯组更好,两组比较差异有统计学意义(P值均0.05)。患者治疗48周后恩替卡韦组血糖及糖化血红蛋白分别为(7.53±1.13)mmol/L和(7.23±0.64)%,阿德福韦酯组血糖及糖化血红蛋白分别为(8.34±1.12)mmol/L和(7.79±0.84)%,两组比较差异均有统计学意义(t值分别为3.220、3.354,P值均0.05)。治疗后恩替卡韦组肝脏硬度值为(16.86±5.67)k Pa,阿德福韦酯组为(19.47±5.32)k Pa,两者比较差异有统计学意义(t=2.123,P0.05)。结论恩替卡韦组患者通过更好的改善肝功能、促进肝细胞修复,使肝糖原代谢改善,对患者血糖调节有帮助,最终血糖控制优于阿德福韦酯组。     

Efficacy of adefovir dipivoxil in the treatment of lamivudine-resistant hepatitis B virus genotype C infection.

BACKGROUND AND AIMS: Adefovir dipivoxil (ADV) is a nucleotide analogue that is known to be effective for lamivudine-resistant hepatitis B virus (HBV) mutants as well as wild-type HBV. The aim of this study is to assess the efficacy of ADV against lamivudine-resistant genotype C HBV mutants. METHODS: Thirty-five patients with breakthrough hepatitis due to lamivudine-resistant HBV received ADV 10 mg daily with discontinuation of lamivudine. Quantitative HBV DNA, HBeAg, liver function test including alanine aminotransferase (ALT) was checked every 4-12 weeks to evaluate the efficacy of ADV. RESULTS: ADV was administered for a median of 48 weeks (range: 24-120 weeks). The rate of serum HBV DNA loss was 68.6%, 80.0%, 84.0%, and 88.2% at weeks 12, 24, 36, and 48, respectively. The rate of serum HBeAg seroconversion was 8.3% and 14.3% at weeks 24 and 48, respectively. The rate of serum ALT normalization at week 48 was 70.6%. Within 32 weeks after stopping ADV therapy, serum HBV DNA levels increased to a median of 378.9 pg/ml in 88.9% of patients, who were treated for a median of 40 weeks. Moreover, in some patients, the ALT level increased to more than five times the upper limit of normal. CONCLUSIONS: Administration of ADV is an effective option for the treatment of patients with lamivudine-resistant genotype C HBV infection.     

阿德福韦酯治疗慢性乙型肝炎合并非酒精性脂肪性肝病的疗效观察

近年来,慢性乙型肝炎(CHB)合并非酒精性脂肪性肝病(NAFLD)的患者在临床上越来越常见。有报道显示27%~76%的CHB患者合并NAFLD[1]。NAFLD常促进原有基础肝病的进展,影响原有肝病治疗的疗效,如HBV感染者合并NAFLD,NAFLD可促进其肝硬化和肝细胞癌的发生[2];慢性丙型肝炎(CHC)患者合并NAFLD,NAFLD可降低非基因3型     

阿德福韦酯联合双环醇片治疗慢性乙型肝炎的疗效和安全性分析

目的研究阿德福韦酯联合双环醇片治疗慢性乙型肝炎的疗效和安全性。方法选择125例曾应用拉米夫定治疗的慢性乙型肝炎患者,随机分2组接受治疗。试验组63例,每日口服阿德福韦酯10mg,同时每日服用双环醇片75mg;对照组62例,仅给予每日口服阿德福韦酯10mg。2组均连续用药48周。观察治疗前后血清氨基转移酶水平及病毒学指标方面的改变。结果2组血清氨基转移酶均明显下降,试验组更为显著(P<0.05或<0.01)。试验组HBV DNA阴转率(58.7%)显著高于对照组(40.3%),P<0.05;HBeAg阴转率(31.8%)显著高于对照组(16.1%),P<0.05;HBeAg血清转换率(19.1%)虽高于对照组(11.3%),但差异无统计学意义。2组均未发生与研究药物相关的不良反应。结论阿德福韦酯与双环醇片联合应用治疗慢性乙型肝炎在肝功能及病毒学方面取得较好疗效且安全。     

阿德福韦酯联合安络化纤丸对乙型肝炎早中期肝硬化治疗效果评价

[目的]评价阿德福韦酯(ADV)联合安络化纤丸治疗乙型肝炎早中期肝硬化的疗效.[方法]145例乙型肝炎早中期肝硬化患者分为对照组(32例)、ADV组(53例)及联合用药组(60例).对照组采用常规护肝及对症治疗;ADV组在对照组基础上加口服ADV 10 mg,1次/d;联合用药组在ADV组基础上加口服安络化纤丸3g,疗程均为1年.比较3组治疗后肝功能、血清肝纤维化指标、乙型肝炎病毒(HBV)-DNA水平、Child-Pugh分值及门静脉压力指标变化.[结果]3组患者治疗后肝功能均不同程度的改善,联合用药组和ADV组肝功能改善优于对照组;联合用药组与ADV组血清白蛋白、球蛋白比较差异有统计学意义(P＜0.01);联合用药组和ADV组肝纤维化指标、HBV-DNA水平和Child-Pugh分值较对照组明显下降,联合用药组肝纤维化指标下降优于ADV组,联合用药组Child-Pugh 分值(5.02±0.76)明显低于ADV组(5.49±1.13),P＜0.01;治疗后联合用药组门静脉内径、脾静脉内径及脾脏厚度较对照组和ADV组明显下降,ADV组脾脏厚度缩小(P＜0.05).[结论]ADV联合安络化纤丸在改善乙型肝炎早中期肝硬化患者肝功能,降低其Child-Pugh评分、肝纤维化指标、门静脉压力指标及HBVDNA水平均有较好的效果.     

拉米夫定联合阿德福韦酯治疗HBeAg阳性慢性乙型肝炎患者48周临床观察

我国现有慢性乙型肝炎（CHB）患者约2000万例,其中HBeAg阳性CHB患者近60%,常常表现为ALT持续或间歇升高,HBV复制活跃,肝组织重度炎症坏死,与HBeAg阴性患者相比,有较高的肝硬化比率[1]及较快速的病情进展[2]。而持续的高病毒载量又与肝细胞癌（HCC）直接相关[3],那么最大限度地长期抑制HBV,减轻肝细胞炎症坏死及纤维化,延缓和减少肝脏失代偿、肝硬化、HCC及其并发症的发生,从而改善生存质量和延长生存时间[4]成为CHB治疗的总体目标。核苷和核苷     

阿德福韦酯治疗HBeAg阳性慢性乙型肝炎临床研究

目的评价阿德福韦酯（ADV）治疗HBeAg阳性慢性乙型肝炎患者48周的疗效和安全性。方法试验按两个阶段进行。第一阶段患者随机进入安慰剂组（A组,20例）或ADV组（B组,34例）双盲治疗12周;第二阶段患者均接受开放的ADV治疗36周。结果治疗12周时,A组和B组HBVDNA总有效率分别为33．3％、76．5％;12周后,随着疗程延长,HBVDNA转阴率、HBeAg转阴率、HBeAg血清转换率、ALT复常率均增加。结论ADV（10mg,1／d,48周）能安全有效地治疗HBeAg阳性慢性乙型肝炎。     

Long-term efficacy of entecavir therapy in chronic hepatitis B patients with antiviral resistance to lamivudine and adefovir

No studies have reported the long-term effects of entecavir switching in patients with multidrug resistance who developed resistance after lamivudine/adefovir sequential therapy. We evaluated the efficacy of 96 weeks of entecavir therapy in patients with resistance to lamivudine/adefovir sequential therapy. In total, 33 patients with chronic hepatitis B virus (HBV) infection with evidence of active viral replication (HBV DNA levels ≥ 10(5) copies/mL) or a history of treatment failure to lamivudine/adefovir sequential therapy between April 2007 and July 2009 were treated with entecavir (1.0 mg daily) for at least 48 weeks. The rates of alanine transaminase (ALT) normalization and HBV DNA negativity were 66.7% (14/21) and 24.2% (8/33) at 48 weeks, respectively. The initial HBV DNA level was the only factor that was inversely associated with serum HBV DNA negativity after 48 weeks of entecavir therapy (P < 0.023). At 96 weeks, the rates of ALT normalization and HBV DNA negativity were 77.8% (7/9) and 16.7% (3/18), respectively. Viral breakthrough occurred in 21.2% (7/33) and 78.9% (15/19) of patients at 48 and 96 weeks, respectively. Patients who achieved a HBV DNA level of <4 log(10) copies/mL at 48 weeks maintained a similar HBV DNA level and a normal ALT level until 96 weeks. Entecavir monotherapy for 96 weeks was not efficacious for patients with lamivudine/adefovir-resistant HBV. The initial HBV DNA level was the only predictive factor for antiviral efficacy. However, patients who achieved a HBV DNA level of <4 log(10) copies/mL with a normal ALT level at 48 weeks should maintain, rather than stop, entecavir therapy.     

膦甲酸钠联合阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎的临床研究

目的 观察膦甲酸钠联合阿德福韦酯治疗拉米夫定耐药的慢性乙型肝炎患者的疗效和安全性.方法 选择拉米夫定耐药的慢性乙型肝炎患者70例,随机分为联合组(膦甲酸钠和阿德福韦酯组)36例,对照组(阿德福韦酯组)34例,完成4周和12周治疗时,分别检测血清HBV DNA水平和肝功能变化.结果 在治疗4周和12周时,联合组肝功能恢复及病毒应答率,均显著高于对照组.两组均未发生与研究药物相关的严重不良反应.两组不良事件发生率无统计学差异.结论 膦甲酸钠联合阿德福韦酯治疗拉米夫定耐药的慢性乙型肝炎,可在生物化学及病毒学方面取得较好疗效,且安全性好.     

Long-term outcomes of add-on adefovir dipivoxil therapy to ongoing lamivudine in patients with lamivudine-resistant chronic hepatitis B

Aim: Add-on adefovir dipivoxil (ADV) therapy has been a standard rescue treatment for patients with lamivudine (LAM)-resistant chronic hepatitis B, but the overall benefits of long-term add-on ADV therapy are still limited. The aim of this study was to evaluate the long-term efficiency of add-on ADV treatment and to explore predictive factors associated with it. Methods: A total of 158 patients with LAM-resistant chronic hepatitis B were included in this retrospective, multicenter, nationwide study in Japan. After confirming LAM resistance, ADV was added to LAM treatment. Three types of events were considered as outcomes: virological response, hepatitis B e antigen (HBeAg) clearance and alanine aminotransferase (ALT) normalization. Virological response was defined as serum hepatitis B virus (HBV) DNA levels of less than 3 log copies/mL. Baseline factors contributing to these outcomes were examined by univariate and multivariate analyses. Results: The median total duration of ADV treatment was 41 months (range, 6–84). The rate of virological response was 90.8% at 4 years of treatment; HBeAg clearance and ALT normalization were achieved by 34.0% and 82.7%, respectively, at the end of follow up. Each outcome had different predictive factors: baseline HBV DNA and albumin level were predictive factors for virological response, history of interferon therapy and ALT level for HBeAg clearance, and sex and baseline albumin level for ALT normalization. Conclusion: Long-term add-on ADV treatment was highly effective in LAM-resistant chronic hepatitis B patients in terms of virological and biochemical responses. Lower HBV replication and lower albumin level at baseline led to better outcomes.