AASLD2014:BeAg阳性HBV高病毒载量: ETV V ADF + LAM

StephenW

1898
A prospective, open-label cohort study comparing the efficacy, safety and drug resistance of entecavir mono-therapy versus de novo combination of lamivudine and adefovir dipivoxil in naïve HBeAg-positive chronic hepatitis B patients with high HBV viral load (The Climber Study): a preliminary analysis

Wei Guo, Di Wu, Peng Wang, Jing-Feng Chen, Yan-hong Xu, Weiming Yan, Ke Ma, Meifang Han, Jianxin Song, Junying Qi, Jiaquan Huang, Yuancheng Huang, Xiping Zhao, Dong Xu, Qin Ning;
Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Background: A substantial proportion of HBeAg-positive chronic hepatitis B (CHB) patients in China has high viral load (HBV DNA levels >108 copies/ml). These patients are particularly likely to display partial treatment responses with less potent nucleos(t)ide analogues with low barrier to resistance. The aim of this study was to compare the efficacy, safety and emergence of resistance mutation to entecavir (ETV) monother-apy versus de novo combination of lamivudine (LAM) and ade-fovir dipivoxil (ADV) in naTve HBeAg-positive CHB patients with high HBV viral load.
Methods: According to the Climber Study protocol, 200-240 NA-naïve HBeAg-positive chronic hepatitis B patients with high HBV viral load (HBV DNA >108copies/ ml by COBAS AmpliPrep/COBAS TaqMan HBV v2.0) were designed to entry this study. Patients were assigned into 2 groups: monotherapy group (ETV 0.5 mg/d) or combination therapy group (LAM 100 mg/d + ADV 10 mg/d) for 96 weeks. At present, 120 patients have been recruited in a single center. Preliminary data of 64 patients (ETV monotherapy N = 28, LAM + ADV combination therapy N = 36) who have completed 48 weeks treatment were analyzed.

Results: Baseline characteristics of patients in both groups were comparable: age (27±7.33 years vs. 34.87±8.52 years, P = 0.617), gender ratio (male/female, 18/10 vs. 30/6 P = 0.081), mean baseline HBV DNA (9.05±0.36 log10 copies/ml vs. 8.94±0.46 log10 copies/ml P = 0.219), mean baseline ALT (147.55±57.46 U/L vs. 139.86±65.25 U/L P = 0.929). After 48 weeks of treatment, the rates of HBV DNA <300 copies/ ml were 50.00% (14/28) in monotherapy group and 27.78% (10/36) in combination therapy group (P = 0.069) while the rates of HBV DNA<100 copies/ml were 39.29% (11/28) in monotherapy group and 13.89% (5/36) in combination therapy group (P = 0.020). No virological breakthrough occurred in the monotherapy group, while 3 patients in the combination therapy group had virological breakthrough with confirmed LAM-resistant variants (1 case rtL180M + rtM204I, 2 cases rtM204I). ALT normalization rates in monotherapy and combination therapy groups were 82.14% (23/28) and 72.22% (26/36), respectively (P = 0.353). The rates of HBeAg loss were 42.86% (12/28) in monotherapy group and 16.67% (6/36) in combination therapy group (P = 0.021). There were no serious adverse events in both groups.

Conclusions: ETV monotherapy compared with de novo combination therapy of LAM and ADV for 48 weeks showed greater HBV DNA suppression in naïve HBeAg-positive chronic hepatitis B patients with high HBV viral load. Both treatment strategies were well tolerated.

Disclosures:

Qin Ning - Advisory Committees or Review Panels: ROCHE, NOVARTIS, BMS,

MSD, GSK; Consulting: ROCHE, NOVARTIS, BMS, MSD, GSK; Grant/Research Support: ROCHE, NOVARTIS, BMS; Speaking and Teaching: ROCHE, NOVAR-TIS, BMS, MSD, GSK

The following people have nothing to disclose: Wei Guo, Di Wu, Peng Wang, Jing-Feng Chen, Yan-hong Xu, Weiming Yan, Ke Ma, Meifang Han, Jianxin Song, Junying Qi, Jiaquan Huang, Yuancheng Huang, Xiping Zhao, Dong Xu

StephenW

1898年
恩替卡韦比较单一疗法的疗效，安全性和耐药性的前瞻性，开放标签队列研究与从头拉米夫定和阿德福韦酯的天真HBeAg阳性慢性乙型肝炎患者HBV高病毒载量（登山者研究）的组合：初步分析

魏过，狄乌彭王京峰陈妍红旭，闫维明，柯妈，张美芳汉，宋建新，俊英齐，黄家泉，元成黄，赵西平，董序，秦宁;
署传染病，同济医院，同济医学院，华中科技大学，武汉，中国研究所

背景：HBeAg阳性慢性乙型肝炎（CHB）患者在中国有相当比例具有高病毒载量（HBV DNA水平>108拷贝/ ml）。这些患者特别有可能显示具有较少的强效核苷（酸）类似物具有低势垒，以抵抗局部治疗的反应。本研究的目的是耐药变异的疗效，安全性和出苗比较恩替卡韦（ETV）monother-疗与从头拉米夫定naTve HBeAg阳性CHB患者的组合（LAM）和ADE-fovir酯（ADV）高的HBV病毒载量。
方法：根据登山研究协议，200-240 NA初治HBeAg阳性慢性乙型肝炎患者HBV高病毒载量（HBV DNA>108copies/ ml的通过COBAS AmpliPrep/ COBAS TaqMan探针HBV V2.0）被设计为入门本研究。患者被分为2组：单药组（ETV0.5毫克/ d）或联合治疗组（LAM100毫克/天+ ADV10毫克/天），96周。目前，120例患者被招募在一个单一的中心。 64例患者中谁已完成治疗48周的初步数据（ETV monother-APY N =28，LAM+ ADV联合治疗N =36）进行了分析。

结果：两组患者基线特征具有可比性：年龄（27±7.33年与34.87±8.52年，P=0.617），性别比例（男/女，18/10与30/6 P =0.081），平均基线HBV DNA（9.05±0.36 log10拷贝/毫升与8.94±0.46 log10拷贝/毫升，P =0.219），平均基线ALT（147.55±57.46 U / L比139.86±65.25 U / LP=0.929）。治疗48周后，HBV DNA的比率<300拷贝/ ml为50.00％（14/28）的单药治疗组27.78％（10/36），联合治疗组（P=0.069），而HBV DNA的比率<100拷贝/ ml为39.29％（11/28）的单药治疗组13.89％（5/36），联合治疗组（P=0.020）。无病毒学突破发生在单药治疗组，而3例患者联合治疗组有病毒学突破与证实LAM耐药变异（1例rtL180M+ rtM204I，2例为rtM204I）。 ALT复常率单药治疗和联合治疗组分别为82.14％（23/28）和72.22％（26/36），分别为（P=0.353）。 HBeAg阴转率分别为42.86％（12/28）的单药治疗组16.67％（6/36），联合治疗组（P=0.021）。有两组无严重不良事件。

结论：恩替卡韦单药治疗LAM和ADV从头联合治疗48周相比，表现出更大的HBV DNA抑制天真HBeAg阳性慢性乙型肝炎患者HBV高病毒载量。这两种治疗方案的耐受性良好。

披露：

秦倪嗯 - 咨询委员会或审查小组：罗氏，诺华，拜耳，

MSD，GSK;咨询：罗氏，诺华，拜耳，MSD，GSK;格兰特/研究支持：罗氏，诺华，拜耳;说起与教学：罗氏，傲华尔-TIS，BMS，MSD，葛兰素史克

下面的人都没有透露：魏郭，狄吴，彭王京峰陈妍红旭，闫维明，柯玛，张美芳汉，宋建新，俊英齐，黄家泉，元成黄，赵西平，董绪