替诺福韦与恩替卡韦对高病毒载量HBeAg阳性慢性乙型肝炎患者的疗效比较

目的观察高病毒载量HBe Ag阳性慢性乙型肝炎(CHB)患者应用替诺福韦(TDF)和恩替卡韦(ETV)治疗48周的临床疗效和安全性。方法选取该院收治的高病毒载量HBe Ag阳性慢性乙型肝炎(CHB)患者80例,随机分成两组,每组40例。TDF组应用TDF,300 mg顿服,1次/d;ETV组应用ETV 0.5 mg顿服,1次/d。观察治疗4、12、24、48周时HBV-DNA转阴率、HBe Ag转阴率、ALT水平等。结果 TDF组治疗4、12、24和48周时HBV-DNA转阴率分别是62.5%、77.5%、95.0%、100%,ETV组分别是25.0%、55.0%、72.5%、95.0%,两组差异有统计学意义(P0.05)。两组治疗4、12周时HBe Ag转阴率差异无统计学意义(P0.05)。TDF组治疗24、48周时HBe Ag转阴率(65.0%、77.5%)高于ETV组(37.5%、50.0%),P0.05。两组在ALT复常率差异无统计学意义(P0.05)。结论 TDF治疗高病毒载量HBe Ag阳性CHB疗效较ETV好,值得临床推广应用。     

替诺福韦和恩替卡韦对老年慢性乙肝病人的抗病毒疗效及对肾功能的影响

目的比较替诺福韦(TDF)与恩替卡韦(ETV)单药治疗老年慢性乙型肝炎(CHB)病人的抗病毒疗效及治疗过程中对肾功能的影响。方法回顾性分析2014～2018年在我院诊治的50例CHB病人的临床资料,其中22例服用TDF,28例服用ETV。收集病人在治疗过程中的病毒学应答、血清肌酐(serum creatitine,SCr)、估算肾小球滤过率(estimated glomerular filtration rate,e GFR)、血清中的视黄醇结合蛋白(retinol-binding protein,RBP)和β2-微球蛋白(β2-microglobulin,β2-MG)等指标的变化情况。比较2组病人的抗病毒疗效及药物对肾功能的影响。结果 2组均出现较好的病毒学应答,且24个月内未见病毒学突破。治疗过程中2组各时点HBV DNA阴转率比较,差异均无统计学意义(P0. 05)。治疗过程中,2组各时点的SCr、e GFR水平差异均无统计学意义(P0. 05);治疗18、24个月时,TDF组的β2-MG水平明显高于ETV组,差异有统计学意义(P0. 05);治疗24个月时,TDF组的RBP水平明显高于ETV组,差异有统计学意义(P0. 05)。结论对于老年CHB病人,ETV和TDF均有较好的抗病毒疗效,但在使用TDF过程中需要定期评估肾功能,对肾功能的评估除SCr、e GFR外,还需要重视RBP和β2-MG。     

对“替诺福韦酯更能降低慢性乙型肝炎患者肝癌发生风险”一文的思考

正慢性乙型肝炎(CHB)抗病毒治疗的总体目标是延缓和减少肝功能失代偿、肝硬化、肝癌及其并发症的发生。当前国内外CHB防治指南均一致推荐恩替卡韦(ETV)和替诺福韦酯(TDF)为一线抗病毒药物,该推荐意见基于已发表的大量临床研究(虽然多数为非头对头研究)。证据显示,ETV和TDF的抗病毒疗效无明显差别,均能大幅度降低慢性乙型肝炎患者肝癌发生风险,且安全性良好。     

富马酸替诺福韦二吡呋酯和恩替卡韦初治慢性HBV感染者的效果比较

目的比较富马酸替诺福韦二吡呋酯(TDF)、恩替卡韦(ETV组)治疗初治慢性HBV感染者的抗病毒疗效。方法收集2014年7月-2015年7月周口市中心医院和南京中医药大学附属八一医院接受TDF或ETV抗病毒治疗且定期随诊的420例初治慢性HBV感染或肝硬化患者,其中接受TDF治疗者184例(TDF组),接受ETV治疗者236例(ETV组)。监测患者的基线值以及治疗后4、8、12、24、48周的实验室指标:肝肾功能指标、血钙、血磷、肌酸激酶、HBV DNA水平、肝炎标志物(HBs Ag、HBeAg、抗-HBe等),以及药物的不良反应。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验或Fisher确切概率法。结果治疗48周时,TDF组与ETV组的HBeAg阳性患者、HBeAg阳性且HBV DNA>6 lg IU/ml患者的HBeAg阴转率比较差异均无统计学意义(P值均>0.05);TDF组与ETV组的HBeAg阴性患者、HBeAg阳性患者、HBeAg阳性且HBV DNA>6 lg IU/ml患者的ALT复常率比较差异均无统计学意义(P值均>0.05)。给予抗病毒治疗后,2组患者HBV DNA水平逐渐下降。治疗48周时,TDF组与ETV组的HBeAg阳性患者中的HBV DNA水平低于检测值下限率分别为75.5%、60.8%,差异有统计学意义(χ2=5.857,P=0.016);TDF组与ETV组HBeAg阳性且HBV DNA>6 lg IU/ml患者中HBV DNA水平低于检测值下限率分别为75.7%、60.5%,差异有统计学意义(χ2=5.722,P=0.017)。96周时,不管是整体还是在亚组(HBeAg阳性、HBeAg阳性且HBV DNA>6 lg IU/ml)间比较,TDF组HBV DNA低于检测值下限率均高于ETV组(93.5%vs 86.9%,χ2=4.921,P=0.027;89.1%vs 76.2%,χ2=6.781,P=0.009;88.3%vs 73.7%,χ2=7.456,P=0.006)。结论在HBeAg阳性慢性HBV感染者中,TDF抑制HBV DNA的能力明显优于ETV,尤其对HBV DNA>6 lg IU/ml的患者。     

替诺福韦相比恩替卡韦可显著改善HBV相关肝细胞癌患者肝切除术后复发

正【据Hepatology 2020年4月报道】题:替诺福韦与恩替卡韦对HBV相关肝细胞癌肝切除术后复发的影响(作者Choi J等)替诺福韦(TDF)和恩替卡韦(ETV)均为目前慢性乙型肝炎(CHB)临床指南中的一线治疗药物,有较高的抗病毒疗效和较低的耐药性。韩国蔚山大学医学院峨山医学中心研究团队的既往研究表明,使用TDF治疗的CHB患者相比于ETV治疗能显著降低肝细胞癌(HCC)的发生风险。该团队进行了一项回顾性队列分析,探讨了TDF与ETV治疗对HBV相关HCC根治性肝切除术后肿瘤复发及总生存率的影响。     

扶正化瘀片联合恩替卡韦治疗慢性乙型肝炎肝纤维化的效果观察

目的观察扶正化瘀片(FZHY)联合恩替卡韦(ETV)治疗慢性乙型肝炎(CHB)肝纤维化的疗效与安全性。方法选取2011年4月—2013年1月在上海交通大学附属瑞金医院和上海中医药大学附属曙光医院2个中心,肝纤维化Ishak分期≥F3的CHB肝纤维化患者52例,分为FZHY联合ETV组(联合组,n=26)和安慰剂联合ETV组(对照组,n=26),分别治疗48周。治疗前后行两次肝穿刺活检,以两组的肝脏病理纤维化Ishak分期逆转率和肝组织学活动指数(HAI)炎症分级改善率等判断疗效,以心电图等为安全性指标。确定3个分析数据集(全分析集、符合方案集、安全数据集),计量资料两组间比较采用t检验或Wilcoxon检验;计数资料组间比较采用CMHχ^2法、χ^2检验或Fisher精确概率法。结果46例患者完成了治疗前后两次肝穿刺,其中联合组22例,对照组24例。治疗48周时,两组Ishak分期下降≥1级患者比例差异有统计学意义(81.8%vs 54.2%,χ^2=5.297,P=0.021)。联合组和对照组HAI分级改善率分别为59.1%、25.0%,差异有统计学意义(χ^2=6.822,P=0.009)。两组不良事件发生率、严重不良事件发生率,不良反应发生率、生命体征安全性分析、实验室安全性指标等比较,差异均无统计学意义(P值均>0.05)。结论在改善肝纤维化和肝脏炎症方面,FZHY联合ETV相较于单用ETV有显著优势,抗病毒联合抗纤维化治疗能够给CHB患者带来更好的肝组织学改善。FZHY联合ETV治疗CHB肝纤维化患者有良好的安全性。     

恩替卡韦治疗慢性乙型肝炎研究进展

慢性乙型肝炎(CHB)是我国常见多发病,目前尚无特效治疗手段,公认有效的抗病毒药物有两类,即干扰素类及核苷(酸)类似物,后者是近10 a来研究的热点.目前,核苷(酸)类似物已有拉米夫定(LVD)、阿德福韦(ADV)、恩替卡韦(ETV)和替比夫定4个品种用于CHB治疗[1],其中ETV是2005年美国食品药品管理局批准治疗CHB的核苷(酸)类似物.现结合文献对ETV治疗CHB的研究进展介绍如下.     

富马酸替诺福韦二吡呋酯治疗慢性乙型肝炎60例

目的:观察富马酸替诺福韦二吡呋酯(TDF)治疗慢性乙型肝炎患者的临床疗效。方法:选取2018年1月至2020年6月在武汉市第七医院接受治疗的慢性乙型肝炎患者120例,随机分为2组,各60例。观察组患者服用TDF 300 mg/d,对照组患者服用恩替卡韦(ETV)0.5 mg/d,疗程均为12个月。比较两组患者治疗前后肝功能、病毒学应答变化情况以及TDF对肾功能的影响。结果:两组患者治疗后HBV DNA水平均较治疗前明显下降(P<0.05);治疗第12个月,TDF组HBV DNA水平低于ETV组(P<0.05),但两者HBV DNA转阴率差异无统计学意义(P>0.05);治疗6个月TDF组患者AST、ALT低于ETV组(P<0.05),治疗12个月尿α1-微球蛋白水平高于ETV组(P<0.05),两组血β2微球蛋白水平无明显改变(P>0.05)。结论:采用TDF治疗慢性乙型肝炎临床疗效显著,但在长期用药过程中有潜在肾损伤风险,应该积极检测肾功能。     

不同抗病毒治疗方案在接受放疗的HBV相关性肝细胞癌中的作用

目的探讨恩替卡韦(ETV)与非恩替卡韦抗病毒治疗对HBV相关性肝细胞癌(HCC)放疗患者HBV定量以及肝功能的影响及可能影响因素,并对总体生存时间进行评估。方法回顾性分析南方医科大学南方医院2011年1月至2016年6月收治的128例HBV相关性HCC患者资料,全部患者均接受肝癌病灶三维适形放疗。根据放疗前抗病毒治疗方案分为ETV组87例和非ETV组41例。放疗结束后每4~8周复查肝功能及HBV DNA定量等,并随访观察两组患者1、2和3年生存率及生存时间。比较两组间乙型肝炎再活动率、肝脏毒性发生率及生存率差异。结果放疗结束后ETV组仅有1例患者(1.15%),而非ETV组有12例患者(29.27%)出现乙型肝炎再活动,差异有统计学意义(P=0.000)。放疗后共51例患者出现肝脏毒性,其中ETV组26例(29.89%),非ETV组25例(60.98%),差异有统计学意义(P=0.008)。ETV组与非ETV组的中位生存时间分别为(19.27±2.53)个月(95%CI:14.305~24.235)和(11.43±5.29)个月(95%CI:1.059~21.801),两组间3年生存率差异无统计学意义(P=0.167)。结论在HBV相关性HCC人群中,放疗前进行ETV抗病毒治疗较非ETV治疗能够更有效预防乙型肝炎再活动以及肝脏毒性的出现,然而不同抗病毒治疗方案对患者的长期生存获益并无差异。     

多潘立酮联合阿米替林治疗功能性消化不良的meta分析

目的对多潘立酮联合阿米替林治疗功能性消化不良的疗效及安全性进行评价。方法计算机检索1991年01月01日至2014年06月01日中国学术期刊全文数据库(CNKI)、维普中文科技期刊数据库(VIP)、万方数据库(WANFANGDATA)、中国生物医学文献数据库(CBMdisc)、Pubmed数据库、Google Book Search等有关多潘立酮联合阿米替林治疗功能性消化不良的随机对照试验(RCT)文献,补充手工检索文献。应用Rev Man5.2软件对入选试验进行Meta分析。结果共8项随机对照试验符合入选标准,共743例功能性消化不良患者,其中接受多潘立酮联合阿米替林治疗共372例患者(试验组),371例患者单用多潘立酮治疗(对照组)。Meta分析结果显示试验组总体有效率(92.5%)明显高于对照组(74.9%,RR:1.23,95%CI:1.16~1.32,P0.000 01),上腹痛腹胀、恶心呕吐、烧心反酸等症状显效率(64.8%)也明显高于对照组(42.0%,RR:1.54,95%CI:1.34~1.77,P0.000 01)。两组不良反应发生率无统计学差异(RR:1.40,95%CI:0.71~2.78,P=0.33)。结论多潘立酮联合阿米替林治疗功能性消化不良疗效优于单用多潘立酮,安全性好,可以成为临床治疗功能性消化不良的一种较佳治疗方案。     

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。     

替诺福韦酯单独与联合恩替卡韦挽救治疗恩替卡韦治疗拉米夫定经治慢性乙型肝炎失败患者疗效比较

目的比较替诺福韦酯单药与联合恩替卡韦对恩替卡韦治疗慢性乙型肝炎拉米夫定经治患者仍应答不佳或发生病毒学突破的挽救方案的临床疗效及安全性。方法将80例恩替卡韦序贯治疗仍效果欠佳的拉米夫定经治慢性乙型肝炎患者随机分为单药组40例和联合组40例。单药组给予替诺福韦酯(300 mg/d)替换治疗;联合组使用替诺福韦酯(300 mg/d)和恩替卡韦(0.5 mg/d)治疗。所有患者均治疗48周,检测基线,治疗12、24和48周时病毒学、生化学、血清学指标。比较两组患者上述治疗时间点的完全病毒学应答率、ALT复常率、病毒学突破率和HBeAg血清学转换率及观察药物不良反应。结果单药组患者治疗48周后完全病毒学应答率、ALT复常率、病毒学突破率、HBeAg血清学转换率分别为85.0%(34/40)、76.2%(16/21)、0、13.1%(3/23),联合组分别为87.5%(35/40)、77.3%(17/22)、0、16.0%(41/25),两组比较差异无统计学意义(均P0.05)。两组患者耐受性均良好,无一例出现严重不良反应而导致停药。结论对于恩替卡序贯治疗后仍应答不佳或发生病毒学突破的拉米夫定经治慢性乙型肝炎患者,替诺福韦酯单药替换恩替卡韦的挽救治疗仍能有效抑制HBV DNA复制,是一种行之有效的优化治疗方案。     

恩替卡韦片联合胸腺肽α1治疗HBeAg阳性乙型肝炎疗效分析

目的 探讨恩替卡韦片联合胸腺肽α1治疗HBeAg阳性慢性乙型肝炎的疗效。方法 140例慢性乙型肝炎患者随机分为2组,治疗组(72例)口服恩替卡韦片,0.5mg/次,1次/d,同时给予胸腺肽α1皮下注射,1.6mg/次,2次/周;对照组(68例)单用恩替卡韦片口服,0.5mg/次,1次/d,2组均连用48周。结果 治疗组HBeAg转阴率为58.33%,HBeAg/抗HBe转换率为38.89%,明显高于对照组(23.53%、11.76%),差异有统计学意义(P均<0.01)。2组HBV DNA转阴率及ALT复常率差异无统计学意义(P均>0.05)。结论 恩替卡韦片联合胸腺肽α1治疗慢性乙型肝炎可提高HBeAg转阴率和HBeAg/抗HBe血清转换率。     

替诺福韦酯与恩替卡韦对慢性乙型肝炎初治疗患者的疗效

目的评估替诺福韦酯与恩替卡韦在治疗慢性乙型肝炎的疗效。 方法纳入2010年6月至2015年6月入住济南军区总医院的慢性乙型肝炎的初治患者100例,采用随机数字表法分为观察组(替诺福韦酯)50例、对照组(恩替卡韦)50例,随访时间12、24个月,比较二者在HBV-DNA转阴率、HBeAg血清学转换率、丙氨酸转氨酶复常率、耐药率、安全性方面是否存在差异。 结果与治疗前比较,观察组与对照组在随访观察12、24个月后各项指标较前明显改善,但二者在HBV-DNA转阴率(32/50 vs.28/50、46/50 vs.42/50)、HBeAg血清学转换率(4/28 vs.6/30、8/28 vs.12/30)、丙氨酸转氨酶复常率(42/50 vs.40/50、49/50 vs.46/50)、耐药率方面未见明显差异;但长期口服恩替卡韦对肾脏影响高于替诺福韦酯组,差异有统计学意义(P<0.05)。 结论替诺福韦酯与恩替卡韦比较,二者在治疗慢性乙型肝炎效果相当,但长期口服药物安全性方面有优势,因此建议长期治疗慢性乙型肝炎临床运用替诺福韦酯作为首选方案。     

Comparison of entecavir and adefovir for the treatment of chronic hepatitis B

The results of several new clinical trials that compared the effectiveness of entecavir (ETV) treatment with that of adefovir (ADV) treatment in patients with chronic hepatitis B (CHB) were published in recent years. However, the numbers of patients included in these clinical trials were too small to draw a clear conclusion as to whether ETV is more effective than ADV. Therefore, a new meta-analysis was needed to compare ETV with ADV for the treatment of CHB. A search of the Cochrane Central Register of Controlled Trials (CCTR), MEDLINE, the Science Citation Index, Embase, the China National Knowledge Infrastructure (CNKI), and the Wanfang Database for relevant studies published between 1966 and 2010 was performed. Trials comparing the use of ETV and ADV for the treatment of CHB were assessed. Of the 2,358 studies screened, 13 randomized controlled clinical trials comprising 1,230 patients (ETV therapy, 621; ADV therapy, 609) were analyzed. The serum hepatitis B virus (HBV) DNA clearance rate obtained in patients treated with ETV was significantly higher than that in patients treated with ADV at the 24th and 48th weeks of treatment (24 weeks: 59.6% vs. 31.8%, relative risk [RR], 1.82, 95% CI: 1.49–2.23; 48 weeks: 78.3% vs. 50.4%, RR, 1.61, 95% CI: 1.32–1.96). The serum HBeAg clearance rate, the HBeAg seroconversion rate, and the ALT normalization rate obtained for patients treated with ETV were also higher than the corresponding values for patients treated with ADV at the 48th week of treatment. The safety profiles were similar between patients treated with ETV and those treated with ADV. The evidence reviewed in this meta-analysis suggests that patients with hepatitis B have a greater likelihood of achieving a viral response and a biomedical response when treated with ETV than when treated with ADV.     

慢性乙型肝炎患者持续应用恩替卡韦治疗3年的疗效

目的 研究恩替卡韦(ETV)治疗慢性乙型肝炎初治患者3年的病毒学、血清学和生物化学的应答情况,以评价其疗效.方法 本研究分两个阶段:第一阶段为ETV和拉米夫定(LAM)的双盲随机对照试验,各有258例和261例入选,分别用ETV 0.5 mg/d或LAM 100 mg/d口服,共96周.第二阶段:经96周治疗,患者如未达到综合应答(bDNA<0.7 mEq/ml,HBeAg阴转持续24周以上.ALT<1.25 X正常值上限)者,或出现病毒学突破或停药后复发者,继续服用ETV1.0 mg/d 48周.共有160例患者完成了连续3年的ETV治疗.持续变量的比较采用了基于线性回归模型的t检验.结果第一阶段结束时(96周),ETV和LAM治疗组患者的HBV DNA阴转率(HBV DNA<300拷贝/ml),ALT复常率和HBeAg血清转换率分别为:79%对比46%(P<0.01),96%对比92%(P=0.06)和21%对比23%.第二阶段:160例持续ETV治疗3年,第144周时,HBV DNA阴性(<300拷贝/ml)的比例为89%,ALT复常率86%,3年的累计HBeAg血清转换率为27%.耐药性:3例在96周时出现了基因型耐药,另有2例在第96～144周时出现了基因型耐药.ETV的耐受性良好,不良反应与LAM相似,但ETV组较少出现ALT反弹.结论 3年的临床试验表明ETV是强效的抗HBV药物,其抑制HBV复制和低耐药性明显优于LAM.     

恩替卡韦治疗拉米夫定失效的慢性乙型肝炎患者3年临床研究

目的评价恩替卡韦对重庆地区拉米夫定治疗失效的CHB患者3年的疗效和安全性。方法选取拉米夫定治疗失效的CHB患者32例,其中恩替卡韦组28例(剂量1.0 mg/d),安慰剂组4例。完成12周的双盲冶疗后,所有患者均接受开放的恩替卡韦1.0mg/d,持续治疗至168周。定期检测血清HBV DNA水平、HBeAg、抗-HBe和肝功能的变化情况。结果在接受恩替卡韦治疗后,患者血清HBV DNA水平对数值的均数在2周内由9.14log10拷贝/ml迅速下降至6.72log10拷贝/ml,其后持续平稳下降,4、8、12、24、48周分别下降至6.28 log10、5.46 log10、5.10 log10、4.49 log10、4.41 log10拷贝/ml,至96周时下降至3.91 log10拷贝/ml,其后下降速度减慢,至144周和168周时分别为4.05 log10、4.21 log10拷贝/ml。HBV DNA>10~5拷贝/ml的百分比治疗前为100%,随着服药时间的延长逐渐下降,在12周时下降至46.43%,其后仍逐渐下降,到96周时仅为17.86%。与其相反,HBV DNA<10~3拷贝/ml的百分比在治疗前为0,从第8周开始逐渐上升(7.14%),12周时为10.71%,尤其在96周明显上升至46.43%,到168周时为57.14%。168周末HBeAg阴转率为10.07%。服用恩替卡韦后ALT下降较迅速,12周后均数达正常水平,且3年内持续低于40 U/L。3年治疗期间,患者不良事件发生率为21%,有1例发生严重不良事件。结论恩替卡韦治疗拉米夫定失效的CHB患者,可明显抑制HBV DNA复制,HBV DNA水平降低迅速且持久;能促进ALT复常;使用安全,耐受性良好。     

Similar efficacy and safety of tenofovir in Asians and non-Asians with chronic hepatitis B

AIM:To compare the efficacy and safety of tenofovir disoproxil fumarate(TDF)in Asian and non-Asian chronic hepatitis B(CHB)patients.METHODS:The efficacy and safety of the initial 48wk of treatment with TDF was compared in a posthoc analysis of combined data from 217 Asians and299 non-Asians included in Studies 102 and 103and a post-approval,open-label trial(Study 123).Patient groups were compared according to baseline hepatitis B e antigen(HBe Ag)status and viral load.The main outcome measures included the proportion of patients who achieved a hepatitis B virus(HBV)DNA level400 copies/m L at Week 48 of treatment.Secondary measures included:HBV DNA and alanine aminotransaminase(ALT)levels over time;proportion of patients with normal ALT levels;proportion of patients with HBe Ag loss/seroconversion and proportion of patients with hepatitis B surface antigen loss/seroconversion;changes in liver histology.Safety and tolerability were evaluated by the occurrence of adverse events(AEs),serious AEs,laboratory abnormalities,discontinuation of the study drug due to AEs,or death.The primary efficacy and safety analysis set included all patients who were randomly assigned to treatment and received at least one dose of study drug.RESULTS:At week 48,similar proportions of Asians and non-Asians reached HBV DNA400 copies/m L(96%of Asian and 97%of non-Asian patients with HBe Ag-negative CHB and 83%of Asian and 79%of non-Asian patients with HBe Ag-positive CHB had HBV DNA)and normal ALT(78%of Asian and 81%of nonAsian patients with HBe Ag-negative CHB and 71%of Asian and 74%of non-Asian patients with HBe Agpositive CHB had normal ALT).On-treatment HBV DNA decline rates were similar between Asians and nonAsians regardless of baseline HBe Ag status and viralload.HBV DNA decline during the first four weeks was2.9 log10 copies/m L in HBe Ag-negative Asians and nonAsians,and in HBe Ag-positive non-Asians,and 3.1log10 copies/m L in HBe Ag-positive Asians.HBe Ag loss and seroconversion was achieved in 14%of Asians vs 26%and 24%,respectively,in non-Asians.Liver histology improved in 77.2%of Asians and 71.5%of non-Asians.No resistance to TDF developed.No renal safety signals were observed.CONCLUSION:TDF demonstrated similar viral suppression,normalization of ALT,improvements in liver fibrosis,and no detectable resistance in Asian and non-Asian patients regardless of baseline HBe Ag status.     

Efficacy and Safety of Telbivudine Compared to Entecavir Among HBeAg+ Chronic Hepatitis B Patients: a Meta-Analysis Study

Background

Hepatitis B virus (HBV) infection is a serious global health problem that is associated with huge social and economic costs. Early antiviral drugs, such as interferon-α2b, peginterferon-α2a, lamivudine, and adefovir, all have their limitations (such as low responses or safety concerns) in clinical application. Telbivudine and entecavir are two of the latest nucleotide drugs and both have been shown to have potent viral suppression. However, in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB), inconsistent results have been generated for efficacy between telbivudine and entecavir. Therefore, evidence-based medical data are required to compare the efficacies, in terms of virological and biochemical responses, and safety between telbivudine and entecavir.

Objectives

We aimed to compare the early antiviral efficacy and safety of telbivudine and entecavir in the treatment of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB).

Patients and Methods

A search for relevant randomized controlled trials (RCTs) on HBeAg-positive CHB patients treated with telbivudine and entecavir for 24 or 52 weeks, published before December 2011, was performed. Primary efficacy endpoint was the cumulative rate of undetectable HBV DNA, and secondary efficacy endpoints included rates of alanine aminotransferase (ALT) normalization, HBeAg disappearance, HBeAg seroconversion and adverse events. Meta-analysis was performed using the Review Manager v5.1.4 software package. We assessed the pooled risk ratios (RRs) and 95% confidence intervals (CIs) using the fixed-or random-effects model.

Results

Six randomized controlled trials (RCTs) involving 555 patients were included. Telbivudine was associated with significantly higher rates of HBeAg disappearance (RR = 1.46, 95% CI: 1.11 - 1.91) and HBeAg seroconversion (RR = 1.76, 95%CI: 1.25-2.48) than entecavir, but had higher adverse events (RR = 2.11, 95%CI: 1.23 - 3.60), compared with entecavir. There was no difference between telbivudine and entecavir in the rate of cumulative undetectable HBV DNA (RR = 0.99, 95% CI: 0.90 - 1.10) and ALT normalization (RR = 0.93, 95% CI: 0.85 - 1.00).

Conclusions

Telbivudine is associated with significantly higher rates of HBeAg disappearance and HBeAg seroconversion than entecavir, whereas entecavir is superior to telbivudine in safety. Both drugs have similar efficacy on rates of cumulative undetectable HBV DNA and ALT normalization.     

Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease

Data are limited on the safety and effectiveness of oral antivirals other than lamivudine and adefovir dipivoxil for treatment of chronic hepatitis B (CHB) in patients with decompensated liver disease. This Phase 2, double-blind study randomized 112 patients with CHB and decompensated liver disease to receive either tenofovir disoproxil fumarate (TDF; n = 45), emtricitabine (FTC)/TDF (fixed-dose combination; n = 45), or entecavir (ETV; n = 22). The primary endpoint was safety; more specifically, tolerability failure (adverse events resulting in permanent treatment discontinuation) and confirmed serum creatinine increase ≥ 0.5 mg/dL from baseline or confirmed serum phosphorus <2 mg/dL. Patients with insufficient viral suppression (e.g., confirmed HBV DNA ≥ 400 copies/mL at week 8 or 24) could begin open-label FTC/TDF but were considered failures in this interim week 48 analysis for efficacy endpoints. Tolerability failure was infrequent across arms: 6.7% TDF, 4.4% FTC/TDF, and 9.1% ETV (P = 0.622) as were confirmed renal parameters meeting threshold 8.9%, 6.7%, and 4.5% (P = 1.000), respectively. Six patients died (none considered related to study drug) and six received liver transplants (none had HBV recurrence). The adverse event and laboratory profiles were consistent with advanced liver disease and complications, with no unexpected safety signals. At week 48, HBV DNA was <400 copies/mL (69 IU/mL) in 70.5% (TDF), 87.8% (FTC/TDF), and 72.7% (ETV) of patients. Proportions with normal alanine aminotransferase were: 57% (TDF), 76% (FTC/TDF), and 55% (ETV). Hepatitis B e antigen (HBeAg) loss/seroconversion occurred in 21%/21% (TDF), 27%/13% (FTC/TDF), and 0%/0% (ETV). Child-Turcotte-Pugh and Modification for End-stage Liver Disease scores improved in all groups. CONCLUSION: All treatments were well tolerated in patients with decompensated liver disease due to CHB with improvement in virologic, biochemical, and clinical parameters.