血清HBeAg滴度及其早期下降幅度预测替比夫定治疗HBeAg阳性慢性乙型肝炎的疗效

目的观察替比夫定(LdT)治疗HBeAg阳性慢性乙型肝炎(CHB)3年的疗效,筛选早期预测疗效的指标。方法 58例HBeAg阳性CHB患者接受LdT治疗3年。结果在治疗12月时,血清ALT复常率和HBV DNA阴转率分别为94.8%和84.5%,而在治疗3月时分别为68.9%和65.5%;随着治疗时间延长,HBeAg阴转率、HBeAg/HBeAb血清转换率及耐药率均明显升高,至36月时分别达50.0%、43.1%和29.3%,而在治疗3月时分别为20.7%、17.2%和0.0%,6月时分别为25.9%、22.4%和1.7%;患者基线HBeAg滴度及疗程3月时HBeAg滴度下降幅度与治疗36月时HBeAg阴转率、HBeAg/HBeAb血清转换率及耐药率明显相关;基线HBeAg≥300S/CO时预测LdT治疗3年后出现耐药的敏感性为74.5%,特异性为78.0%。结论 LdT能有效恢复肝功能,抑制HBV复制和提高HBeAg血清转换,但长时间使用后则耐药率较高;HBeAg基线水平及其下降幅度可早期预测LdT治疗HBeAg阳性CHB患者HBeAg血清转换率及耐药发生率。     

ETV或ADV初治CHB患者的2年疗效观察

目的随机、对照、开放比较恩替卡韦(ETV)或阿德福韦酯(ADV)初治慢性乙型肝炎(CHB)患者2年的疗效。方法选取2007年8月-2007年12月在沈阳市第六人民医院住院的CHB患者60例,按1∶1的比例随机分成2组,分别接受ETV 0.5 mg/d或ADV 10 mg/d口服,疗程至少104周。评价患者96周HBV DNA下降幅度、HBV DNA阴转率、ALT复常率、HBeAg血清转换率、病毒学突破率及应答不佳率。结果 96周时,ETV组HBV DNA水平较基线平均降幅为(6.05±1.99)lg拷贝/ml,高于ADV组的(4.03±3.24)lg拷贝/ml(t=2.192,P=0.005)。ETV组HBV DNA阴转率高于ADV组(80%vs 40%,χ2=10.000,P=0.002)。ALT复常率、HBeAg阳性患者HBeAg血清转换率两组比较差异无统计学意义。ETV组无病毒学突破,应答不佳率为23.3%。ADV组病毒学突破率为13.3%,应答不佳率为73.3%(χ2=-2.053、15.017,P=0.04、<0.001)。结论 ETV相对于ADV可早期快速抑制病毒。不论是ETV还是ADV,24周评估原发性无应答及48周评估部分病毒学应答是优化治疗中应关注的截点。     

六味五灵片联合替比夫定治疗HBeAg阳性慢性乙型肝炎疗效观察

目的：观察六味五灵片联合替比夫定（LdT）治疗 HBeAg 阳性慢性乙型肝炎（CHB）的疗效。方法将127例 HBeAg阳性 CHB 患者随机分为治疗组69例和对照组58例。治疗组口服六味五灵片和 LdT,对照组口服甘草酸二胺胶囊和 LdT,疗程均为24周。结果在治疗24周后,治疗组患者血清 ALT、AST 和 TBIL 分别为28.9±16.8 U/L、23.8±15.9 U/L 和29.8±12.7μmol/L,显著低于对照组（43.1±18.0） U/L、（46.1±17.4） U/L 和（35.5±16.8）μmol/L,P＜0.05）;治疗组 HBV DNA 阴转率为89.9%,显著高于对照组（74.1%,P＜0.05）,差异有统计学意义。结论六味五灵片联合 LdT 能够明显改善 HBeAg 阳性 CHB 患者的肝功能,促使 HBV DNA 和 HBeAg 转阴。     

恩替卡韦治疗HBeAg阴性与HBeAg阳性慢乙肝和肝硬化感染患者疗效观察

目的观察国产恩替卡韦(ETV)对HBeAg阴性与HBeAg阳性慢性乙型肝炎(CHB)和肝硬化感染患者的临床治疗效果。方法 97例慢性HBV感染患者,依据血清HBeAg检测结果分为HBeAg阴性组与HBeAg阳性组;根据病情程度分为CHB组与肝硬化组。给予ETV 0.5mg,1次/天(口服),研究周期共48周。观察指标:基线及治疗4、12、24、48周时血清HBV-DNA水平、ALT和TBIL变化。结果 ETV治疗前,HBeAg阴性组与HBeAg阳性组、慢乙肝组与肝硬化组,基线水平检测指标差异均无统计学意义(P0.05)。ETV治疗4周时HBeAg阴性组与HBeAg阳性组的HBV-DNA完全抑制率分别是28%、8%,差异有统计学意义(P0.05)。12、24、48周时HBeAg阴性组与HBeAg阳性组HBV-DNA完全抑制率分别是68%、85%、91%与56%、76%、84%,差异均无统计学意义(P0.05)。ETV治疗4周时HBeAg阴性组HBV-DNA水平下降对数值(1.91±1.00lgIU/ml)高于HBeAg阳性组(1.07±0.78lgIU/ml),差异有统计学意义(P0.05)。结论国产恩替卡韦对初治HBeAg阴性慢乙肝患者的早期病毒应答率优于HBeAg阳性慢乙肝患者,长期病毒应答率无统计学差异;对慢性乙肝与肝硬化患者抗病毒疗效没有差异。     

替比夫定治疗HBeAgeAg阳性慢性乙型肝炎疗效的预测指标

目的探讨替比夫定治疗HBeAg阳性慢性乙型肝炎（CHB）48周的疗效及其预测指标。方法采用替比夫定（LdT）600 mg/d治疗78例HBeAg阳性CHB患者48周,从性别、年龄、ALT和HBV DNA基线、早期病毒学应答（治疗12周时HBV DNA转阴）为预测因素,分析其对治疗48周疗效的影响。结果性别、年龄与治疗8～48周时HBV DNA转阴无相关性（P〉0.05）;5 ULN≤ALT≤10 ULN组治疗24、36及48周时HBV DNA转阴率高于2 ULN≤ALT≤5 ULN组（P〈0.05,P〈0.01）;HBV DNA 106～105拷贝/ml组治疗48周时ALT复常率和HBV DNA转阴率高于HBV DNA〉107拷贝/ml组（P〈0.05）;早期病毒学应答组治疗48周时HBeAg阴转率ALT复常率和HBV DNA转阴率也高于非应答组（治疗12周时HBV DNA≥500拷贝/ml）（P〈0.05）。结论 ALT、HBV DNA基线、早期病毒学应答可能可以作为预测替比夫定抗HBV疗效的指标     

聚乙二醇干扰素α-2a治疗HBeAg阳性慢性乙型肝炎部分应答患者序贯替比夫定治疗疗效观察*

目的 探讨在聚乙二醇干扰素α-2a治疗的HBeAg阳性慢性乙型肝炎(CHB)部分应答患者序贯替比夫定继续治疗的临床疗效。方法 2016年1月～2017年2月我院感染病科收治的63例HBeAg阳性CHB患者在应用聚乙二醇干扰素α-2a治疗48周后呈部分应答的患者,其中31例在停止干扰素治疗后接受替比夫定序贯治疗48周,另32例则停药观察48周。两组随访24周。结果 在治疗或观察24周、48周和随访24周,序贯治疗组患者血清HBeAg转阴率分别为22.5%、25.8%和35.4%,均显著高于停药观察组的0.0%、3.2%和3.2%(P<0.05),在治疗或观察48周和随访24周,序贯治疗组血清HBV DNA转阴率为90.3%和87.0%,显著高于停药观察组的34.3%和18.7%(P<0.05),ALT复常率为96.7%和90.3%,显著高于停药观察组的75.0%和25.0%(P<0.05);在治疗或观察48周和随访24周,序贯治疗组血清HBV DNA水平为(2.6±0.3)lgIU/mL和(1.9±0.1)lgIU/mL,显著低于停药组的【(4.5±0.7)lgIU/mL和(5.5±0.2)lgIU/mL,P<0.05】,血清ALT水平分别为(56.3±2.4)IU/L和(43.3±3.1)IU/L,显著低于停药组【分别为(60.1±7.2)IU/L和(71.3±2.8)IU/L,P<0.05】,在随访24周,序贯治疗组血清HBsAg水平为(2.0±0.2)lg IU/mL,显著低于停药组【(2.6±0.3)lg IU/mL,P<0.05】;序贯治疗组在48周治疗期间,其中9例(29.0%)患者在服用替比夫定期间出现血清肌酸激酶升高现象,在治疗10～13周后下降至正常水平。结论 对于经聚乙二醇干扰素α-2a治疗结束后呈部分应答的血清HBeAg阳性CHB患者序贯应用替比夫定继续治疗48周,发现能够有效提高患者血清HBV DNA转阴率和ALT复常率,且安全性较高。     

六味五灵片联合恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者的疗效观察

目的探讨恩替卡韦（ETV）联合六味五灵片治疗HBeAg阳性慢性乙型肝炎（CHB）患者的疗效。方法 102例HBeAg阳性CHB患者随机分为两组,联合治疗组50例每日服用ETV0.5mg,六味五灵片1.5g,每日3次;对照组52例每日服用ETV0.5mg。分别观察服药第12、24、52周时肝肾功能、血清HBeAg及HBV DNA水平。结果治疗52周结束时联合治疗组和对照组ALT复常率分别为88%和69.23%（P〈0.01）;HBeAg/HBeAb血清学转换率分别为34%和25%（P〈0.05）。结论联合治疗组在ALT复常及HBeAg/HBeAb血清学转换方面均优于对照组,六味五灵片联合恩替卡韦可以起到很好的协同抗病毒的作用。     

替比夫定治疗HBeAg阳性慢性乙型肝炎疗效观察

目的观察替比夫定治疗HBeAg阳性慢性乙型肝炎患者HBeAg血清转换与HBV DNA应答快慢的相关性。方法在48例经替比夫定治疗48周的慢性乙型肝炎患者,常规观察应答反应。结果本组替比夫定治疗患者在治疗48周结束时,48例患者中有30例(62.5%)HBV DNA转阴,18例HBV DNA持续阳性。在30例HBV DNA转阴患者中,发生HBeAg血清转换16例(53.3%)。其中在12周内发生HBV DNA转阴的15例中,发生HBeAg血清学转换12例(80%);在24周以后发生HBV DNA持续转阴的15例患者中,仅有1例(6.7%)发生HBeAg血清学转换;发生HBeAg血清学转换的患者,谷丙转氨酶均恢复正常。结论 24周内HBV DNA快速下降到不可测水平是预测替比夫定治疗HBeAg阳性慢性乙型肝炎发生HBeAg血清转换的重要预测因子。     

恩替卡韦治疗合并非酒精性脂肪肝的慢性乙型肝炎临床疗效观察

[目的]探讨非酒精性脂肪肝(NAFLD)对恩替卡韦(ETV)治疗慢性乙型肝炎(CHB)临床疗效的影响。[方法]纳入乙型肝炎病毒e抗原(HBeAg)阳性CHB患者273例,按是否合并NAFLD分为2组,其中合并NAFLD的CHB患者123例为观察组,单纯CHB患者150例为对照组。2组患者均予ETV抗病毒治疗至少72周,并行定期临床随访。[结果]在ETV治疗12周和24周时观察组患者的HBV-DNA清除率、HBeAg血清阴转率及谷丙转氨酶(ALT)复常率均显著低于对照组(P0.05);在36周和48周时观察组患者的ALT复常率仍显著低于对照组(P0.05),但2组间HBV-DNA清除率和HBeAg血清阴转率差异无统计学意义;在60周和72周时2组间的HBV-DNA清除率、HBeAg血清阴转率及ALT复常率差异均无统计学意义。Kaplan-Meier曲线示,观察组患者的HBV-DNA清除、HBeAg血清阴转及ALT复常均明显晚于对照组(P0.05)。[结论]NAFLD既可影响ETV治疗CHB的病毒学、血清学及生物化学应答,又是ETV抗病毒获得病毒学和血清学应答基础上生物化学应答欠佳的重要原因,而延长ETV治疗疗程则有助于改善合并NAFLD的CHB患者的生物化学应答。     

替比夫定治疗HBeAg阳性慢性乙型肝炎的疗效及相关预测因子的Logistic回归分析

目的观察替比夫定（LdT）治疗HBeAg阳性慢性乙型肝炎（CHB）患者3年的疗效,应用Logistic回归探讨HBeAg血清学转换的预测因子。方法收集58例采用LdT治疗的HBeAg阳性CHB患者,分析其性别、年龄、基线ALT水平、基线HBV DNA载量、基线HBeAg和HBsAg滴度与治疗3年时ALT复常率、HBV DNA阴转率、HBeAg阴转率和HBeAg血清转换率的相关性;采用Logistic回归分析HBeAg血清转换的相关因素。结果治疗3年时ALT复常率为84.48%,HBV DNA阴转率为70.69%,HBeAg阴转率为50.00%,HBeAg血清转换率为43.10%。与ALT≤2倍正常值上限（2×ULN）相比,基线ALT〉5×ULN的患者HBeAg转换率显著增高（P〈0.05）;与HBeAg≤100（S/CO）组相比,基线HBeAg〉200 S/CO的患者HBeAg的阴转率和血清转换率均显著下降（P〈0.05）;与HBV DNA≤6 log拷贝/ml组相比,HBV DNA〉7 log拷贝/ml的患者HBV DNA转阴率、HBeAg转阴率和HBeAg转换率下降显著（P〈0.05）;患者性别、年龄及基线HBsAg滴度对以上疗效指标无影响（P〉0.05）。多因素Logistic回归分析发现仅基线HBeAg滴度低的患者更易出现HBeAg血清学转换。结论 LdT能有效恢复肝功能,抑制HBV复制和提高HBeAg血清转换;基线HBeAg滴度可预测LdT治疗HBeAg阳性CHB患者的HBeAg血清转换率。     

替比夫定与阿德福韦酯治疗HBeAg阳性慢性乙型肝炎的疗效观察

目的比较替比夫定与阿德福韦酯治疗HBeAg阳性慢性乙型肝炎的疗效和安全性。方法 175例HBeAg阳性慢性乙型肝炎患者被随机分为替比夫定组（85例）和阿德福韦酯组（90例）,比较两组在治疗后48周时的疗效。结果治疗后12周、24周、36周和48周时,替比夫定治疗患者HBV DNA水平低于阿德福韦酯组（P〈0.01）,HBV DNA转阴率和ALT复常率均高于阿德福韦酯组（P〈0.05或P〈0.01）;治疗后12周、24周和36周HBeAg转阴或血清学转换率和完全应答率也高于阿德福韦酯组（P〈0.05或P〈0.01）;治疗48周,替比夫定组有2例,阿德福韦酯组有1例出现病毒学反弹;两组均有良好的安全性。结论替比夫定较阿德福韦酯有更强的抑制HBV作用,其治疗可提高HBeAg转阴或血清学转换率和完全应答率。     

核苷（酸）类似物初始治疗慢性乙型肝炎患者疗效和安全性的网络Meta分析

目的 比较核苷（酸）类似物单药初始治疗慢性乙型肝炎患者的疗效和安全性。方法 计算机检索阿德福韦酯（ADV）、恩替卡韦（ETV）、拉米夫定（LAM）、替比夫定（LdT）和富马酸替诺福韦酯（TDF）初始治疗慢性乙型肝炎患者的随机对照试验。应用Stata13进行网络Meta分析。采用固定效应模型和效应指标相对危险度（RR)及其95%可信区间（CI）进行分析。结果 纳入14篇RCTs,总计5720例患者,其中ETV 治疗1396例,LdT 治疗982例,LAM 治疗2015例,TDF 治疗783例,ADV 治疗544例。经1年治疗,在HBV DNA低于检测下限方面, TDF为88.5%,ETV为79.9%,LdT为55.4%,LAM为19.9%,ADV为6.2%;在ALT复常方面, ETV为95.9%,TDF为56.6%,LdT为44.6%,ADV为34.1%,LAM为18.8%;在HBeAg消失方面, LdT为80.2%,TDF为76.2%,ETV为42.5%,LAM为27.4%,ADV为23.7%;在HBeAg血清学转换方面,LdT为79.9%,TDF为66.5%,ETV为39.1%,LAM为35.5%,ADV为29.0%。结论 TDF在HBV DNA低于检测下限方面疗效最好,ETV在ALT复常方面疗效最好,LdT在HBeAg消失/HBeAg血清学转换方面疗效最好。     

恩替卡韦治疗慢性乙型肝炎过程中应答不佳相关因素分析

目的探讨年龄、性别、体质量指数(BMI)、治疗前HBV DNA载量、ALT、AST、APTT、PT、HBsAg定量、HBeAg定量、P区基因变异、治疗过程中ALT、AST、HBV DNA下降幅度等因素在恩替卡韦治疗慢性乙型肝炎(CHB)过程中与应答不佳的关系。方法选择128例CHB患者,HBeAg阳性患者84例,HBeAg阴性患者44例。均初次使用恩替卡韦进行抗病毒治疗。治疗前检测上述基线因素及P区变异,治疗过程中ALT、AST、HBV DNA下降幅度等指标。在治疗后4、12、24周分别检测HBV DNA、ALT、AST、HBsAg定量、HBeAg定量。根据治疗24周时HBV DNA载量,分为完全应答组(HBV DNA最低检测值下限)和应答不佳组(HBV DNA下降2 lg,但仍﹥最低检测值下限)。统计分析上述指标与治疗应答的关系。结果年龄、性别、APTT、PT、ALT、AST与治疗应答无明显相关性(P0.05)。BMI、治疗前HBV DNA载量、HBsAg定量与治疗应答呈负相关,BMI高、高HBV DNA载量、HBsAg高水平患者多应答不佳(P0.05)。HBeAg阳性为应答不佳的危险因素(OR=5.431;r=0.358)。HBeAg阳性患者,治疗24周时,应答不佳组HBV DNA下降幅度大(P0.05),rtM204V/I变异率10%时易出现应答不佳(P0.05),rtL180M变异与应答无明显相关性(P0.05)。HBeAg阴性患者,治疗12周时,完全应答组HBV DNA下降幅度大(P0.05),rtM204V/I变异,rtL180M变异均与应答无明显相关性(P0.05)。结论 BMI高、治疗前高HBV DNA载量、HBsAg定量高水平、HBeAg阳性、rtM204V/I变异率10%的HBeAg阳性慢性乙型肝炎患者应用恩替卡韦抗病毒治疗时易出现应答不佳。     

Effect of nucleoside analog‐interferon sequential therapy on patients with acute exacerbation of chronic hepatitis B

Aim: Nucleoside analog (NA)‐interferon (IFN) sequential therapy may enable the long‐term control of chronic hepatitis B (CHB) and the withdrawal of the nucleoside analog. We evaluated the efficacy of NA‐IFN sequential therapy for acute exacerbation of CHB. Methods: A total of 12 patients with acute exacerbation of CHB, nine of whom were positive for hepatitis B e antigen (HBeAg), were enrolled in this study. All the patients were treated with lamivudine 100 mg/day alone for 20 weeks, then with both IFN‐α 6 megaunits three times per week and lamivudine for 4 weeks, and lastly, with IFN‐α alone for 20 weeks. Patients whose serum alanine aminotransferase (ALT) level was normalized, whose serum hepatitis B virus (HBV) DNA level decreased to less than 5 log copies/mL, and HBeAg level was absent 24 weeks after the end of treatment were defined as having sustained virological response (SVR). The other patients were defined as having no response (NR). Results: Four out of nine (44.4%) HBeAg‐positive and all three HBeAg‐negative patients achieved SVR. The levels of serum alanine aminotransferase (ALT), HBV DNA and HBV core‐related antigen were similar between SVR and NR patients at baseline. Three of four patients (75.0%) whose serum HBeAg became negative at the end of treatment achieved SVR, while one of five (20.0%) whose serum HBeAg remained positive achieved SVR. Conclusion: NA‐IFN sequential therapy for patients with acute exacerbation of CHB enables the withdrawal of treatment and is particularly effective for patients whose serum HBeAg has become undetectable by the end of the IFN treatment.     

Efficacy and safety of long term entecavir in chronic hepatitis B treatment naïve patients in clinical practice

Background and aims. Entecavir (ETV) is effective and safe in patients with chronic hepatitis B in the short term, but its long term efficacy and safety has not been established.Material and methods. We evaluated HBV DNA clearance, HBeAg/antiHBe and HBsAg/antiHBs seroconversion rates in HBeAg-positive and negative NUC naïve HBV patients treated with ETV for more than 6 months, and predictors of response.Results. A hundred and sixty nine consecutive patients were treated with ETV for a median of 181 weeks. 61% were HBeAg positive, 23% were cirrhotics, and mean HBV-DNA levels were 6,88 ± 1,74 log₁₀ lU/mL. Overall, 156 (92%) patients became HBV DNA undetectable, 92 (88%) HBeAg positive and 64 (98%) HBeAg negative patients. Seventy four (71%) patients cleared HBeAg after a median of 48 weeks of treatment, 23 (14%) patients cleared HBsAg (19 HBeAg positive and 4 HBeAg negative, p 0.025) after a median of 96 weeks of treatment, and 22 (13%) patients developed protective titers of anti-HBs. At the end of the study, 35 (20%) patients had discontinued therapy: 33 HBeAg positive and 2 HBeAg negative; 9 of them (26%) developed virological relapse after a median of 48 weeks of stopping treatment. None of the patients had primary non response and one patient developed breakthrough. Two patients developed HCC, three underwent liver transplantation and 3 deaths were attributable to liver-related events. No serious adverse events were reported.Conclusion. Long term ETV treatment showed high virological response rates, and a favorable safety profile for NUC-naive HBeAg-positive and negative patients treated in clinical practice.     

Telbivudine protects renal function in patients with chronic hepatitis B infection in conjunction with adefovir‐based combination therapy

Previous studies have demonstrated that the treatment of chronic hepatitis B (CHB) infection with adefovir (ADV) can impair renal function. In contrast, treatment with telbivudine (LdT) improves renal function in CHB patients. The aim of this study was to evaluate the renoprotective effect of LdT in CHB patients receiving ADV‐based combination therapy. The effects of treatment with ADV + LdT on renal function were compared to those resulting from treatment with ADV + entecavir (ETV), ADV + lamivudine (LAM), ADV alone and ETV alone. The consecutive cohort analysis included 831 CHB patients who received ADV + LdT, ADV + LAM, ADV + ETV, ADV alone or ETV alone for 96 weeks. Alterations in estimated glomerular filtration rate (eGFR) were compared between the five groups using a linear mixed‐effects model. HBV DNA levels were also compared between the five groups during the 96‐week period. Among the five treatment groups, significant improvements in eGFR were observed in the ADV + LdT and ADV + LAM groups over time (P < 0.001 for each group compared with baseline eGFR). In patients with a baseline eGFR between 50 and 90 mL/min, the change in eGFR was the most significant in the ADV + LdT group (+0.641 mL/min; P < 0.001). Age, gender, baseline eGFR and treatment option were significant predictive factors for eGFR changes. In conclusion, our results suggest that the combination therapy of LdT and ADV is significantly associated with renoprotective effects in CHB patients when compared with other ADV‐based combination or single therapies.     

Potential Effects of Telbivudine Versus Entecavir on Renal Function in Patients With Chronic Hepatitis B Virus Receiving Glucocorticoids Therapy

Data remains limited about the optimal nucleos(t)ide analogue therapy for patients infected with hepatitis B virus (HBV) while treated with glucocorticoids because of kidney diseases. We aim to evaluate the safety and efficacy of long‐term antiviral therapy with telbivudine (LdT) and entecavir (ETV) in this specific population. In this prospective randomized controlled study, a total of 60 patients with both kidney diseases and chronic hepatitis B were randomly divided into LdT group and ETV group. We analyzed changes in estimated glomerular filtration rate (eGFR), variation in HBV DNA, seroconversion of hepatitis B e antigen (HbeAg) and hepatitis B surface antigen (HBsAg). During the 18 month follow‐up period, serum HBV DNA load was decreased significantly at 3, 6, 12, 18 months, compared to the pre‐treatment value in both LdT and ETV cohorts. No patients achieved HBeAg loss‐seroconversion or HBsAg loss‐seroconversion with ETV therapy whilst one patient experienced HBeAg and HBsAg loss‐seroconversion with LdT therapy. No significant changes in eGFR were seen in patients with ETV therapy compared to baseline. However, eGFR increased 7.43, 18.97 mL/min/1.73m², respectively at 12 and 18 months in LdT group and the changes were significant compared to baseline. Further analysis also demonstrated that eGFR significantly improved 11.8, 23.25 mL/min/1.73m² at 12 and 18 months in LdT group for patients with impaired renal function. LdT is superior to ETV in patients with chronic hepatitis B and kidney diseases because of the renal protection it confers by increasing eGFR.     

Prediction of response to entecavir therapy in patients with HBeAg-positive chronic hepatitis B based on on-treatment HBsAg, HBeAg and HBV DNA levels

Summary. Quantitative hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) assays are emerging as effective tools of on‐treatment predictors of response to antiviral agents, in addition to monitoring serum HBV DNA levels. However, the dynamic relationship between quantitative HBsAg, as well as HBeAg and HBV DNA, and the predictability of subsequent clinical outcomes during entecavir (ETV) therapy remain unclear. Eighty‐two patients with HBeAg‐positive chronic hepatitis B (CHB) received ETV therapy for ≥3 years. Virologic response (VR) after 3 years of ETV therapy was achieved in 73 (89.0%) patients. Among baseline and on‐treatment factors, on‐treatment HBV DNA levels performed better with respect to the prediction of response than HBsAg and HBeAg levels. Especially, the performance of absolute values of HBV DNA with respect to response was superior to HBV DNA decline from the baseline. The best predictive value was an absolute HBV DNA level of 2.3 log₁₀ IU/mL at month 6 (areas under the curve [AUROC], 0.977; 95% CI, 0.940–1.000; P < 0.001). HBeAg seroconversion after 3 years of therapy was achieved in 26 (31.7%) patients. On‐treatment HBeAg levels performed better with respect to the prediction of seroconversion than HBsAg and HBV DNA levels. The best cut‐off value for the HBeAg level at month 12 for the prediction of seroconversion was 0.62 log₁₀ PEIU/mL. Although the HBsAg level at baseline is often used to predict the antiviral potency of entecavir, on‐treatment HBV DNA and HBeAg levels are more helpful for prediction of subsequent clinical outcomes in HBeAg‐positive CHB patients with entecavir treatment.     

Relapse rates in chronic hepatitis B naïve patients after discontinuation of antiviral therapy with entecavir

Registration studies show entecavir (ETV) to be effective and safe in NUC‐naïve patients with chronic hepatitis B, but relapse rates after treatment discontinuation have not been well established. Relapse rates and predictors of relapse were evaluated in naïve HBeAg‐positive and HBeAg‐negative patients treated with ETV. Treatment duration was defined according to international guidelines. Virological relapse was defined as reappearance in serum of hepatitis B virus (HBV) DNA to >2000 IU/mL after discontinuation of treatment. A hundred and sixty‐nine consecutive patients were treated for a median 181 weeks. 61% were HBeAg positive, 23% had cirrhosis, and mean HBV DNA level was 6.88 ± 1.74 log₁₀ IU/mL. Ninety‐two per cent became HBV DNA negative; 71% of HBeAg+ve patients became HBeAg negative and 68% anti‐HBe positive; 14% became HBsAg negative and 13% anti‐HBs positive. At the end of the study, 36 patients discontinued treatment: one due to breakthrough associated with resistant variants and 35 (20%) due to sustained virological response; 33 of these patients developed HBeAg seroconversion and 18 HBsAg seroconversion. Median off‐treatment time was 69 weeks. Nine patients (26%), all HBeAg positive at baseline, developed virological relapse after a median 48 weeks off‐treatment, 3 of them showed HBeAg reversion and 4 lost anti‐HBe. No patient with HBsAg seroconversion relapsed. HBeAg clearance after week 48 of treatment was associated with an increase risk of relapse. After ETV discontinuation, HBsAg seroconversion was maintained in 100% of the patients, HBeAg seroconversion maintained in 90%, and virological relapse rate was 24%.     

联合拉米夫定继续治疗阿德福韦酯初治HBeAg阳性慢性乙型肝炎不应答患者3年疗效观察

目的观察阿德福韦酯初始治疗HBeAg阳性慢性乙型肝炎不应答患者加用拉米夫定治疗3年的临床疗效。方法 62例HBeAg阳性慢性乙型肝炎患者初始口服国产阿德福韦酯治疗,由于未出现病毒学应答,分别在治疗12周(A组18例)、24周(B组20例)和48周(C组24例)加用拉米夫定继续治疗,观察3年的疗效。结果在治疗3年末,A组、B组和C组患者HBV DNA转阴率分别为83.3%、60.0%和95.8%,A组和C组疗效明显高于B组(P<0.05);ALT复常率分别为94.4%、100.0%和100.0%,差异无显著性(P>0.05);HBeAg转阴率分别为66.7%、20.0%和41.7%,A组明显高于C组和B组;HBeAg血清学转换率分别为33.3%、5.0%和8.3%,A组明显高于B组和C组(P<0.05)。结论阿德福韦酯初治未出现病毒学应答的患者可随时加用拉米夫定联合治疗。