阿德福韦酯联合拉米夫定或恩替卡韦治疗慢性乙型肝炎和肝硬化出现肾损害后的处理

目的探讨阿德福韦酯(ADV)联合拉米夫定(LAM)或恩替卡韦(ETV)治疗慢性乙型肝炎(CHB)和乙型肝炎肝硬化(LC)出现肾性低磷血症等不良反应后的治疗方案。方法对2012年1月至2017年6月在山东省淄博市中心医院感染科就诊的采用ADV联合LAM或ETV治疗的CHB和LC患者进行定期检查,对出现肾损害的患者调整抗病毒治疗方案并随访,分析抗病毒药物调整前后血磷、肾小球滤过率估计值(eGFR)、乙型肝炎病毒DNA(HBV-DNA)等的变化。结果发现肾损害患者22例,包括接受ADV和LAM治疗(LAM耐药后加ADV,简称add-on方案)的CHB和LC患者(Child-Pugh A级)21例、接受ADV和ETV治疗的CHB患者1例,肾损害主要表现为低磷血症(100%),8例(36.4%) eGFR下降;21例采用add-on方案的患者HBV-DNA低于检测下限,1例应用ETV联合ADV治疗的患者,乙型肝炎病毒DNA高于检测下限,耐药检测提示ETV耐药。对应用add-on方案的21例患者中的7例换用ETV1. 0mg/d(每天1. 0mg)治疗、3例换用ETVO. 5mg/d治疗;8例停LAM换用替比夫定(LdT),继用ADV治疗;3例停LAM、ADV,换用LdT联合替诺福韦酯(TDF)治疗;应用ETV联合ADV治疗的1例患者,停用ETV和ADV,换用LdT 0. 3g/d和TDF 0. 15g/d治疗。调整方案后20例(90.9%)患者1-4个月内血磷水平恢复正常;eGFR下降的8例中有6例在6个月内恢复正常;ETV 1.0mg/d组和LdT联合ADV组药物调整前后血磷、eGFR对比差异均有显著性(P<0.05);21例(95.5%)患者治疗方案调整后HBV-DNA仍低于检测下限,对ETV耐药的1例(4. 5%) 1个月后HBV-DNA检测不到。结论长期应用ADV联合LAM或ETV治疗的小部分CHB和LC患者可出现低磷血症等不良反应,发生后及时调整抗病毒药物,换用LdT联合抗病毒治疗方案或对采用add-on方案者单独应用恩替卡韦治疗可改善病情,且维持抗病毒的疗效。     

拉米夫定、恩替卡韦治疗慢加急性肝衰竭近期疗效比较

目的:评价拉米夫定(LAM)、恩替卡韦(ETV)治疗HBV相关慢加急性肝衰竭(acute-on-chronic liver failure,ACLF)的近期疗效.方法:回顾性分析64例HBV相关的ACLF患者经LAM或ETV治疗后病毒学应答、免疫学应答情况及主要肝功能指标、MELD评分的变化.结果:24例接受LAM治疗,40例接受ETV治疗.治疗后ETV组的早期血清HBV DNA水平下降速度及阴转率优于LAM组[4周时血清HBV DNA水平下降幅度(2.80±0.92)log10拷贝/mL vs(2.01±0.70)log10拷贝/mL,t=2.428,P=0.023;HBV DNA阴转率61.3%(19/31)vs 27.8%(5/18),x2=5.118,P=0.024],但免疫学应答、主要肝功能指标及MELD评分改善程度差异无显著性(均P＞0.05).结论:ETV治疗ACLF较LAM能更快更强抑制HBV复制,但在免疫学应答、改善肝功能及短期预后方面未显示出优势.     

恩替卡韦与阿德福韦酯治疗慢性乙型肝炎的早期病毒学反应观察

目的:观察恩替卡韦(ETV)与阿德福韦酯(ADV)治疗慢性乙型肝炎的早期血清生化指标与病毒学反应。方法:试验组口服恩替卡韦,每日0·5mg;对照组口服阿德福韦酯,每日10mg。定期检测肝功能和血清HBV DNA定量,以服药前数据作为基线值,服药后第4、12、24周分别作为快速病毒学反应(RVR)、初始病毒学反应(IVR)、早期病毒学反应(EVR)。结果:两组服药前HBV DNA基线水平无显著差异(P>0·05)。ETV组RVR、IVR、EVR期的HBV DNA降幅(logcp/ml)分别为2·60±0·85、3·22±1·24、3·06±1·29,显著高于同期ADV组的1·69±0·82、2·03±1·10、2·00±1·25(P<0·05);ETV组早期病毒学应答率和HBV DNA下降至检测水平以下者比例分别达到82%、51%,高于ADV对照组的69%、36%;ETV原发无应答比例(18%)低于ADV组(31%)。两组ALT完全复常的比例均为64%。ETV组有2例治疗后1月ALT显著升高,而在治疗3月后ALT完全恢复正常,血清HBV DNA下降至检测水平以下。结论:ETV组抗HBV作用相对较强,但与ADV的生化学应答相近。少数恩替卡韦治疗者出现短暂ALT显著升高,似乎其病毒学早期反应更好。     

恩替卡韦和阿德福韦治疗乙型肝炎5年疗效比较

目的观察恩替卡韦（ETV）、阿德福韦（ADV）治疗慢性乙型肝炎（CHB）5年的临床疗效,并探讨乙型肝炎病毒及生化水平等对核苷类抗病毒药物物的影响。方法选择CHB患者100例并随机分为两组,恩替卡韦组53例,阿德福韦组47例,分别给予ETV和ADV治疗。ETV组和ADV组治疗前后分别检测两组患者HBV DNA、HBV血清学标志物及生化指标。结果两组患者一般资料比较差异均无统计学意义（P〉0.05）。治疗后,ETV组和ADV组各检测时点HBV DNA低于检测限率比较差异均有统计学意义（P〈0.05）;两组患者各时点的丙氨酸氨基转移酶复常率及HBeAg、HbeAb血清转化率比较差异均无统计学意义。两药的耐药性和不良反应比较差异均无统计学意义（P〉0.05）。结论恩替卡韦较阿德福韦抑制病毒速度快;HBeAg（＋/-）组患者均出现明显的病毒抑制;两者5年内的耐药性相似,且HBeAg和HBeAb血清转换率均呈逐年上升趋势。     

乙型肝炎病毒逆转录酶基因突变的临床意义

目的 分析服用核苷酸类似物的乙肝患者逆转录酶(RT)基因突变模式及其与生化指标的相关性,探讨该基因突变的临床意义。方法 采用半巢式PCR对634例来自武汉地区的乙肝病毒感染者血浆HBV进行扩增后,Sanger测序法进行基因序列分析; 将RT基因突变组与野生组和各表型突变组中患者的谷氨酸氨基转移酶(ALT)、乙肝病毒e抗原(HBeAg)和HBV DNA阳性率作比较。结果 在测序成功的622例患者中,144例(23.15%)发生RT基因突变。他们在11个位点(rtM204,rtL180,rtA181,rtN236,rtV173,rtL80,rtM250,rtS202,rtV207,rtV214和rtV84)出现碱基突变。在突变组中,患者的ALT,HBeAg和HBV DNA阳性率显著高于非突变组(P<0.05)。表型分析显示:拉米夫定(LAM)耐药最常检测到,占52.78%,其次为阿德福伟(ADV)耐药占27.78%和恩替卡韦(ETV)耐药占6.94%,多重耐药LAM+ADV于18例患者中检出12.5%。多重耐药组患者ALT,HBeAg和HBV DNA阳性率高于其他耐药组(P<0.05); ADV耐药组患者ALT,HBeAg和HBV DNA阳性率高于LAM,ETV耐药组。结论 HBV RT区域的突变形式与血清学指标ALT,HBeAg和HBV DNA阳性状态有显著关联,该基因的突变形式可用作患者临床表现的指示指标。     

替诺福韦和恩替卡韦治疗HBeAg阳性初治慢性乙型肝炎的疗效分析

目的探讨替诺福韦治疗HBeAg阳性初治慢性乙型肝炎的疗效及对血清HBV DNA及ALT的影响。方法将94例于我院就诊的HBeAg阳性初治慢性乙型肝炎患者,依照随机数字法分为T组和E组各47例。所有患者均行饮食指导、保肝等基础治疗,T组在其基础上给予TDF(替诺福韦)口服,E组给予ETV(恩替卡韦)口服。对比2组用药前后不同阶段血清HBV DNA及ALT水平、HBV DNA转阴和HBe抗原转阴情况、ALT(丙氨酸转氨酶)复常率和用药安全性情况。结果 T组用药后不同阶段血清HBV DNA及ALT水平均低于E组(P0.05);用药1年后T组HBV DNA与HBe抗原转阴率均高于E组(P0.05),但2组间ALT复常率比较,无显著差异(P0.05);2组用药期间不良事件发生率比较,无明显差异(P0.05)。结论替诺福韦治疗HBeAg阳性初治慢性乙型肝炎疗效显著,能有效降低血清HBV DNA及ALT水平,促进HBe抗原和乙肝病毒DNA的转阴,且用药安全性较高。     

联合方案治疗拉米夫定耐药HBeAg阳性慢性乙型肝炎患者的临床观察

[目的]观察拉米夫定（LAM）联合阿德福韦酯（ADV）与恩替卡韦（ETV）联合ADV治疗LAM耐药HBeAg阳性慢性乙型肝炎（CHB）的临床疗效.[方法]选择LAM耐药的HBeAg阳性CHB患者50例,随机分为LAM联合ADV组（A组）,ETV联合ADV组（B组）,每组各25例,观察两组在治疗前及治疗12、24、48周时HBV DNA载量、谷丙转氨酶（ALT）水平、HBV血清标志物变化.[结果]两组在治疗12、24、48周HBV DNA均较治疗前下降（P＜0.05）;治疗48周时A组与B组的HBV DNA阴转率和ALT复常率率分别为76.0％与88.0％、80.0％与92.0％,两组间差异无统计学意义（P＞0.05）;治疗24周HBV DNA阴转率B组高于A组（分别为84.0％,52.0％）,差异有统计学意义（P＜0.05）;治疗24周ALT复常率B组高于A组（分别为80.0％,52.0％）,差异有统计学意义（P＜0.05）;治疗过程中两组HBeAg阴转率比较差异无统计学意义（P＞0.05）;未出现严重不良反应及病毒学突破.[结论]LAM联合ADV与ETV联合ADV治疗LAM耐药HBeAg阳性CHB患者均能获得良好的临床疗效且安全性良好;ETV联合ADV能快速抑制HBV DNA及降低ALT,早期HBV DNA阴转率及ALT复常率高于LAM联合ADV.     

恩替卡韦对拉米夫定耐药慢性乙型肝炎患者的治疗效果

目的:观察恩替卡韦(博路定)对拉米夫定耐药的慢性乙型肝炎(CHB)患者的疗效及对乙型肝炎病毒脱氧核糖核酸(HBV DNA)的影响.方法:36例对拉米夫定耐药的CHB患者用博路定治疗,疗程均为6个月,每2个月检测肝功能、乙型肝炎病毒血清学标志物、HBVDNA.其中10例患者进行治疗前、后肝穿刺活检.结果:在治疗后6个月,患者的肝功能、乙型肝炎病毒血清学标志物、HBV DNA差异有显著性(P<0.05),大部分患者肝组织病理有所改善.结论:博路定能提高对拉米夫定耐药CHB患者的疗效.     

干扰素联合恩替卡韦治疗慢性乙型肝炎的近期疗效观察

目的探讨干扰素(IFN)联合恩替卡韦(ETV)治疗慢性乙型肝炎(CHB)的疗效。方法选取2016年1月至2018年1月接受治疗的138例CHB患者为受试对象,按照入院顺序随机分为研究组、IFN组及ETV组,每组46例。IFN组予以单独使用IFN进行治疗,ETV组予以单独使用ETV,研究组联合使用IFN及ETV。比较三组患者治疗12、24及48周时的病毒学完全应答率,比较三组患者治疗24周后的治疗结局[血清丙氨酸氨基转移酶(ALT)复常率、HBV-DNA不可检测率、乙肝e抗原(HBeAg)阴转率、HBeAg转换率],统计三组患者不良反应发生情况。结果治疗12周、24周及48周时,研究组患者病毒学完全应答率均明显高于IFN组及ETV组患者(P0.05)。治疗24周后,研究组患者ALT复常率、HBV-DNA不可检测率、HBeAg阴转率及HBeAg转换率均明显高于IFN组及ETV组(P均0.05)。三组患者不良反应总发生率比较差异未见统计学意义(P0.05)。结论联合应用IFN及ETV对CHB患者疗效较好,是治疗CHB的安全有效方案。     

恩替卡韦治疗乙型肝炎肝硬化病毒耐药的临床观察

目的观察恩替卡韦治疗乙型肝炎肝硬化48周后的疗效及病毒耐药位点变异情况。方法收集近2年门诊或住院患者,其中恩替卡韦治疗乙型肝炎肝硬化患者19例,采用恩替卡韦0.5 mg/d治疗,同时阿德福韦治疗组(10mg/d)23例、替比夫定治疗组(600 mg/d)15例、拉米夫定治疗组(100 mg/d)14例,于治疗48周后观测其肝功能、Child-Pugh分级以及血清HBV DNA自基线下降的水平。结果治疗48周后各治疗组患者肝功能、Child-Pugh分级以及血清HBV DNA自基线下降的水平与治疗前比较均有显著性差异,而且恩替卡韦未出现耐药方面的相关表现。结论恩替卡韦能改善活动性乙型肝炎肝硬化肝功能,疗效与其他核苷类似物比较无显著性差异,但耐药方面表现较其他药物为优。     

Randomized trial of entecavir plus adefovir in patients with lamivudine-resistant chronic hepatitis B who show suboptimal response to lamivudine plus adefovir

A substantial proportion of patients with lamivudine-resistant hepatitis B virus (HBV) show suboptimal virologic response during rescue combination treatment with lamivudine plus adefovir. In this randomized active-control trial, 90 patients with serum HBV DNA levels of >2,000 IU/ml after at least 24 weeks of treatment with lamivudine-plus-adefovir therapy for lamivudine-resistant HBV were randomized to combination treatment with entecavir plus adefovir (ETV+ADV, n = 45) or continuation of lamivudine plus adefovir (LAM+ADV, n = 45) for 52 weeks. At baseline, patients' mean serum HBV DNA level was 4.60 log(10) IU/ml (standard deviation [SD], 1.03). All 90 patients completed 52 weeks of treatment. At week 52, the proportion of patients with serum HBV DNA levels of <60 IU/ml, the primary endpoint, was significantly higher in the ETV+ADV group than in the LAM+ADV group (n = 13, 29%, versus n = 2, 4%, respectively; P = 0.004). The mean reduction in serum HBV DNA levels from baseline was significantly greater in the ETV+ADV group than in the LAM+ADV group (-2.2 log(10) IU/ml versus -0.6 log(10) IU/ml, respectively; P < 0.001). At week 52, additional mutations causing resistance to adefovir or entecavir were analyzed in all patients with detectable HBV DNA by restriction fragment mass polymorphism assays and detected in none of the ETV+ADV group but in 15% of patients in the LAM+ADV group (P = 0.018). Safety and adverse event profiles were similar in the two groups. In conclusion, entecavir-plus-adefovir combination therapy provides superior virologic response and favorable resistance profiles, compared with the continuing lamivudine-plus-adefovir combination, in patients with lamivudine-resistant HBV who fail to respond to lamivudine-plus-adefovir combination therapy.     

深圳地区乙型肝炎病毒基因型分布与核苷类药物治疗后相应突变位点筛查的研究

目的了解深圳地区乙肝病毒基因型分布特点以及拉米夫定（LMV）和阿德福韦（ADV）两种药物治疗后相关指标变化情况。方法276例HBeAg阳性患者采用实时荧光定量PCR法检测HBV DNA的含姑,免疫化学发光法检测HBeAg的相对含量．DNA反向斑点杂交芯片技术检测HBV DNA基因型与LMV常见耐药位点、ADV常见耐药位点,全自动生化测定谷丙转氦酶。随机选取未发牛以上突变位点慢性病例各96例,分别以LMV和ADV两种药物进行治疗,于治疗前和治疗3、12个月检测HBV DNA、HBeAg及ALT的含量,并在治疗12个月时筛查2组耐药突变位点。结果276例HBeAg阳性标本有270例可以进行分型,其中B型138例（50．0％）、C型96例（34．8％）、D型10例（3．6％）、B＋C混合型26例（9．4％）、末分碰6例（2．2％）。在治疗3个月时LMV组HBV DNA与HBeAg含量下降速度和阴转率以及ALT下降明显高于ADV组（P〈0．05）;但在治疗第12个月时LMV组HBV DNA含节下降速度和阴转率反而低于ADV组。LMV组有20例发生耐药他点,而ADV组无一例发生位点突变。结论深圳地区乙肝分型主要以B、C两型为主．B型略占优势,B＋C混合型也占有一定比例,核苷类药物LAM及ADV单药治疗慢性乙肝患者均有较好的疗效,但两种药物比较,短期效果LAM优于ADV,随着用药时间延长,耐药突变基因的逐渐出现,ADV长期治疗效果反而要优于LAM。     

Selection of hepatitis B virus polymerase mutations in HIV-coinfected patients treated with tenofovir

BACKGROUND: Tenofovir (TDF) is an adenosine nucleotide analogue that has been approved for the treatment of HIV-1 infection. It also shows activity against hepatitis B virus (HBV) in patients with or without lamivudine (LAM)-associated mutations. Development of clinical or virological HBV breakthrough during TDF therapy has not been reported so far. The aim of this study was to analyse the HBV polymerase (pol) from HIV/HBV-coinfected patients with detectable serum levels of HBV DNA during treatment with TDF for longer than 6 months. METHODS: The HBV pol was sequenced from 43 patient's serum before and during TDF therapy. Phenotypic analyses were performed using HBV replication-competent plasmids carrying unique mutations selected under TDF therapy. RESULTS: Mean exposure to LAM was 35.3 +/- 27.5 months and to TDF 11.2 +/- 6.7 months. Genotypic analyses from 21 of the patients revealed LAM-associated mutations, and a further two patients developed a novel mutation, rtA194T, along with LAM-resistance-associated mutations. Phenotypic analyses revealed that constructs harbouring rtA194T combined with rtL180M and rtM204V displayed an over 10-fold increase in the IC50 for TDF compared with the wild type. CONCLUSION: The selection of HBV mutations in HBV/HIV-coinfected patients failing TDF therapy is an unlikely event within the first 12 months of treatment. However, HBV from two of the 43 patients treated with TDF for more than 12 months was found to contain one novel mutation located distal to the catalytic site of the HBV pol. In vitro, rtA194T conferred a reduced susceptibility to TDF in the presence of LAM-associated mutations.     

Efficacy of Entecavir-Tenofovir Combination Therapy for Chronic Hepatitis B Patients with Multidrug-Resistant Strains

The emergence of multidrug-resistant (MDR) strains of hepatitis B virus (HBV) is a major concern. This study aimed to investigate the efficacy and safety of combination therapy with entecavir (ETV) plus tenofovir disoproxil fumarate (TDF) against MDR HBV. To adjust for differences in baseline characteristics, inverse probability weighting (IPW) using propensity scores for the entire cohort and weighted Cox proportional hazards models were applied. Ninety-three consecutive patients who were treated with ETV-TDF combination therapy for >6 months were included; at baseline, 45 were infected with HBV strains with genotypic resistance to lamivudine (LAM) and ETV (the LAM/ETV-R group), 28 with strains resistant to LAM and adefovir (ADV) (the LAM/ADV-R group), and 20 with strains resistant to LAM, ETV, and ADV (the LAM/ETV/ADV-R group). The median duration of rescue therapy was 13.0 (range, 6.7 to 31.7) months. Seventy-four of 93 patients (79.6%) achieved complete virologic suppression, after a median of 4.5 (95% confidence interval, 3.0 to 6.0) months. The cumulative probability of complete virologic suppression at month 6 was 63.6% (55.7%, 75.0%, and 65.0% in the LAM/ETV-R, LAM/ADV-R, and LAM/ETV/ADV-R groups, respectively). During the treatment period, these probabilities were not significantly different across the resistance profiles before and after IPW (P = 0.072 and P = 0.510, respectively). In multivariate analysis, a lower baseline HBV DNA level, but not resistance profiles, was an independent predictor of complete virologic suppression. Renal dysfunction was not observed during the treatment period. In conclusion, rescue therapy with ETV-TDF combination is efficient and safe in patients infected with MDR HBV strains regardless of the antiviral drug resistance profiles.     

Efficacy of Adefovir-Based Combination Therapy for Patients with Lamivudine- and Entecavir-Resistant Chronic Hepatitis B Virus Infection

Treatment strategies for entecavir (ETV)-resistant chronic hepatitis B (CHB) patients are not yet well established. The aim of this study was to evaluate overall antiviral efficacy and to compare the efficacy of combination therapy with adefovir (ADV) plus nucleoside analogues (lamivudine [LAM], telbivudine [LdT], or ETV) in patients infected with LAM- and ETV-resistant hepatitis B virus (HBV) variants. Virologic, biochemical, and serologic responses during combination therapy with ADV plus nucleoside analogues were assessed. Propensity score analysis was used to select a matched group of patients for the comparison of rescue therapy regimens. A total of 67 consecutive patients were analyzed. Complete virologic suppression was achieved in 27 patients. The overall cumulative incidence of complete virologic suppression at month 24 was 47.4%: 44.3% in the LAM or LdT plus ADV group and 51.4% in the group given ETV and ADV. There was no significant difference between these two groups (P = 0.234). The cumulative incidences of complete virologic suppression were still comparable between the two groups selected and matched using the propensity score model (P = 0.419). Virologic breakthrough was observed in 9 patients, and rtA181V substitution was newly detected in one patient. Hepatitis B e antigen (HBeAg) negativity and lower baseline HBV DNA level were associated with complete virologic suppression in univariate analysis. In multivariate analysis, lower baseline HBV DNA level remained an independent predictor. In conclusion, combination therapy with ADV plus nucleoside analogues fails to show sufficient antiviral efficacy in CHB patients with resistance to both LAM and ETV. Further study is warranted to evaluate the efficacy of a more potent tenofovir-based regimen in such patients.     

Comparison of the antiviral activity of adefovir and tenofovir on hepatitis B virus in HIV-HBV-coinfected patients

BACKGROUND: Characteristics and factors influencing viral decay under tenofovir (TDF) and adefovir (ADV) need to be determined in HIV-HBV-coinfected patients. METHODS: This open-label study compared the HBV dynamics in 85 HIV-HBV-coinfected patients initiating an antiretroviral regimen, either including TDF or associated with ADV. The first 6-month change in viral load was analysed using mixed linear models. The adjusted hazards ratio, comparing the rates of undetectable HBV DNA between treatments, was calculated using a Cox proportional hazard model. RESULTS: The HBV DNA decay, adjusted for baseline HBV viral load was more pronounced in patients treated with TDF than with ADV at 12 months (66% versus 53%, P=0.0001). Patients in the TDF group presented a steeper slope of decline at 1.1 (95% confidence interval [CI] 0.9-1.3), compared with 0.8 (95% CI 0.6-1.0) in the ADV group (P=0.036). The mean time to HBV DNA undetectability was 19.3 months (95% CI 16.7-22.0) with TDF and 25.9 months (95% CI 21.1-30.7) with ADV. When adjusted for hepatitis B virus e antigen, HBV DNA and alanine aminotransferase levels at baseline, the influence of treatment on time to HBV DNA undetectability remained in favour of TDF versus ADV (hazard ratio=2.79, 95% CI 1.05-7.40, P=0.039) CONCLUSIONS: TDF influenced more strongly the early-phase HBV DNA kinetics than ADV. This is associated with a sustained antiviral activity in the TDF group, in which patients reached the threshold of HBV undetectability at a faster rate and in a larger proportion than those taking ADV.     

Virological response and incidence of adefovir resistance in lamivudine-resistant patients treated with adefovir dipivoxil

BACKGROUND AND AIMS: The incidence of adefovir dipivoxil (ADV) resistance in patients with lamivudine (3TC)-resistant mutants who received ADV therapy remains unclear. The aims of this study were to determine the virological response to ADV, the incidence and the risk factors of ADV resistance, and the associated factors of initial virological response (IVR) in lamivudine-resistant patients. PATIENTS AND METHODS: Forty-six consecutive lamivudine-resistant chronic hepatitis B patients treated with ADV for more than 12 months with or without 3TC overlapping were prospectively examined for virological response and adefovir resistance. RESULTS: IVR was documented in 24 (52.2%) of patients. Of the 46 patients, 11 had ADV resistance (5 rtN236T, 5 rtA181T, 1 rtA181T and rtN236T). The cumulative incidence of ADV resistance at month 6, 12, 18 and 24 was 0%, 6.5%, 24.6% and 38.3% respectively. Compared with those without ADV resistance, patients with ADV resistance had a significantly higher rate of liver cirrhosis. Based on Cox regression analysis, the significant risk factor of ADV resistance was younger age (OR=0.92, 95% CI=0.86-0.99, P=0.023) and liver cirrhosis (OR=5.3, 95% CI=1.12-25.09, P=0.036). In addition, patients with ADV resistance were associated with higher HBV DNA levels and lower HBV DNA reduction in first 6 months of ADV treatment than those without ADV resistance. CONCLUSION: Only half of our patients achieved IVR on ADV treatment. The incidence of ADV resistance was high in 3TC-resistant patients treated with ADV.