AASLD2014:恩替卡韦在治疗早期ALT上升是罕见的，不需要治疗适

StephenW

1872
Early hepatic flares during ETV treatment are rare and do not require treatment adaptation in chronic hepatitis B without cirrhosis
Pauline Arends1, Heng Chi1, Ivana Carey2, Ashley S. Brown3, Massimo Fasano4, David J. Mutimer5, Katja Deterding6, Ye H. Oo5, Joerg Petersen7, Florian van Bommel8, Robert J. de Knegt1, Jurrien G. Reijnders1, Thomas Berg8, Tania M. Welzel9, Stefan Zeuzem9, Teresa Santantonio4, Heiner Wedemeyer6, Maria Buti10, Pierre Pradat11, Fabien Zoulim11, Bettina E. Hansen1,12, Harry L. Janssen13,1;
1Gastroenterology and hepatology, Erasmus MC, Rotterdam, Netherlands; 2Hepatology and Gastroenterology, Kings College, London, United Kingdom; 3Hepatology and Gastro-enterology, Imperial College, London, United Kingdom; 4Clinic of Infectious diseases, University of Foggia, Foggia, Italy; 5NIHR Bio-medical Research Unit and Centre for Liver Research, Queen Elizabeth Hospital, Birmingham, United Kingdom; 6Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany; 7IFI Institute, Asklepios Klinik St. Georg, Hamburg, Germany; 8Hepatology, University Clinic Leipzig, Leipzig, Germany; 9Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universtitat, Frankfurt am Main, Germany; 10Hepatology, Hospital Vall de Hebron, Barcelona, Spain; 11Hepatology, Hopital de la Croix-Rousse Hospices Cicils de Lyon, Lyon, France; 12Public Health, Erasmus MC, Rotterdam, Netherlands; 13Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada

Background Flares during NA therapy are usually associated with antiviral resistance or cessation of therapy. Since ETV resistance is rare and therapy is rarely stopped, we investigated the frequency and outcome of flares during ETV therapy in CHB. Methods All HBV monoinfected patients treated with ETV from 11 large European centers (VIRGIL Study Group) were studied. Flares were defined as an ALT level >3× compared to baseline with an absolute ALT level > 3×ULN. Results 733 patients were treated for a median of 168 (IQR 84-213) weeks with ETV monotherapy. Nineteen patients (3%) developed a flare after a median of 26 (10-83) weeks. None of the patients developed genotypic resistance and in only one case non-compliance was documented. Flares were relatively mild with a median ALT peak of 7.3×ULN (IQR 4.5-10-1). Among patients with flares, one developed HBeAg seroconversion, and one lost HBeAg. Baseline HBeAg status (HR 2.91, 95%CI 1.17-7.23, p=0.02), HBV DNA (HR 1.31, 95%CI 1.06-1.63, p=0.01), platelet count (HR 1.0, 95%CI 0.98-1.00, p=0.04) and albumin (HR 0.91, 95%CI 0.84-0.99, p=0.03) were associated with development of a flare. Nine patients (47%) had a flare during decline of HBV DNA, three patients (16%) with a stable HBV DNA and seven (37%) with an increase of HBV DNA. Flares during a decline of HBV DNA occurred after a median of 10 weeks (IQR 4-21), which was significantly earlier compared to flares during a stable or increase in HBV DNA (76 weeks, IQR 29-149) (p<0.001). Conclusion Flares during ETV are rare. Flares in patients occurring before week 26 of therapy were almost exclusively present during continued decline of HBV DNA. In these patients ETV can be continued under strict monitoring as the majority have a good biochemical- and virologic outcome.

Disclosures:

Ivana Carey - Grant/Research Support: Gilead, BMS, Roche; Speaking and Teaching: BMS

Ashley S. Brown - Advisory Committees or Review Panels: MSD, Roche, Bris-tol-Myers-Squibb, Gilead, Janssen, Abbvie, Achillion; Speaking and Teaching: MSD, Roche, Bristol-Myers Squibb, Gilead, Janssen, Abbvie

Joerg Petersen - Advisory Committees or Review Panels: Bristol-Myers Squibb, Gilead, Novartis, Merck, Bristol-Myers Squibb, Gilead, Novartis, Merck; Grant/ Research Support: Roche, GlaxoSmithKline, Roche, GlaxoSmithKline; Speaking and Teaching: Abbott, Tibotec, Merck, Abbott, Tibotec, Merck

Florian van Bommel - Advisory Committees or Review Panels: Gilead Sciences Inc., Roche Pharmaceutics; Grant/Research Support: Biopredictive; Speaking and Teaching: Bristol-Myers Squibb, Janssen, Roche Pharmaceutics, Gilead Sciences Inc.

Robert J. de Knegt - Advisory Committees or Review Panels: MSD, Roche, Norgine, Janssen Cilag; Grant/Research Support: Gilead, MSD, Roche, Janssen Cilag, BMS; Speaking and Teaching: Gilead, MSD, Roche, Janssen Cilag

Jurrien G. Reijnders - Consulting: Gilead ; Speaking and Teaching: Bristol Myers-Squibb

Thomas Berg - Advisory Committees or Review Panels: Gilead, BMS, Roche, Tibotec, Vertex, Jannsen, Novartis, Abbott, Merck; Consulting: Gilead, BMS, Roche, Tibotec; Vertex, Janssen; Grant/Research Support: Gilead, BMS, Roche, Tibotec; Vertex, Jannssen, Merck/MSD, Boehringer Ingelheim, Novartis; Speaking and Teaching: Gilead, BMS, Roche, Tibotec; Vertex, Janssen, Merck/MSD, Novartis, Merck, Bayer

Tania M. Welzel - Advisory Committees or Review Panels: Novartis, Janssen, Gilead, Abbvie, Boehringer-Ingelheim+

Stefan Zeuzem - Consulting: Abbvie, Boehringer Ingelheim GmbH, Bristol-Myers Squibb Co., Gilead, Novartis Pharmaceuticals, Merck & Co., Idenix, Janssen, Roche Pharma AG, Vertex Pharmaceuticals

Heiner Wedemeyer - Advisory Committees or Review Panels: Transgene, MSD,

Roche, Gilead, Abbott, BMS, Falk, Abbvie, Novartis, GSK; Grant/Research

Support: MSD, Novartis, Gilead, Roche, Abbott; Speaking and Teaching: BMS,

MSD, Novartis, ITF, Abbvie, Gilead

Maria Buti - Advisory Committees or Review Panels: Gilead, Janssen, Vertex, MSD; Grant/Research Support: Gilead, Janssen; Speaking and Teaching: Gilead, Janssen, Vertex, Novartis

Fabien Zoulim - Advisory Committees or Review Panels: Janssen, Gilead, Novira, Abbvie, Tykmera, Transgene; Consulting: Roche; Grant/Research Support: Novartis, Gilead, Scynexis, Roche, Novira; Speaking and Teaching: Bristol Myers Squibb, Gilead

Harry L. Janssen - Consulting: Abbott, Bristol Myers Squibb, Debio, Gilead Sciences, Merck, Medtronic, Novartis, Roche, Santaris; Grant/Research Support: Anadys, Bristol Myers Squibb, Gilead Sciences, Innogenetics, Kirin, Merck, Medtronic, Novartis, Roche, Santaris

The following people have nothing to disclose: Pauline Arends, Heng Chi, Massimo Fasano, David J. Mutimer, Katja Deterding, Ye H. Oo, Teresa Santantonio, Pierre Pradat, Bettina E. Hansen

StephenW

1872
恩替卡韦在治疗早期肝耀斑是罕见的，不需要治疗适应于无肝硬化的慢性乙肝
宝莲Arends1，恒Chi1，王菀之Carey2，阿什利南Brown3，马西莫Fasano4，戴维·J·Mutimer5，卡佳Deterding6，叶阁下OO5，约尔格Petersen7，弗洛里安面包车Bommel8，罗伯特·德Knegt1，Jurrien湾Reijnders1，托马斯Berg8 ，塔尼亚米Welzel9，斯特凡Zeuzem9，邓丽君Santantonio4，海纳Wedemeyer6，玛丽亚Buti10，皮埃尔Pradat11，法比安斯基Zoulim11，贝蒂娜大肠杆菌Hansen1,12，哈利属Janssen13,1;
1Gastroenterology和肝病，伊拉斯谟的MC，荷兰鹿特丹; 2Hepatology和消化内科，国王学院，伦敦，英国; 3Hepatology和胃enterology，帝国理工学院，伦敦，英国;传染病4Clinic，福贾，福贾，意大利的大学; 5NIHR生物医学研究单位及中心肝病研究，伊利沙伯医院，伯明翰，英国; 6Gastroenterology，肝脏和内分泌科，医学院汉诺威，汉诺威，德国; 7IFI研究所，阿斯科勒比俄斯KLINIK圣乔治，汉堡，德国; 8Hepatology，大学医院莱比锡，莱比锡，德国; 9Medizinische KLINIK1，KLINIKUM DER约翰·沃尔夫冈·歌德Universtitat，美因河畔法兰克福，德国; 10Hepatology，医院瓦尔代希伯伦，巴塞罗那，西班牙; 11Hepatology，总医院德拉十字鲁塞收容所Cicils里昂，里昂，法国; 12Public健康，伊拉斯谟的MC，荷兰鹿特丹; 13Toronto中心肝病大学健康网络，多伦多，加拿大

NA治疗过程中的背景耀斑通常与病毒性或停止治疗有关。由于恩替卡韦耐药是罕见的，治疗是很少停下来，我们恩替卡韦治疗慢性乙型肝炎过程中调查耀斑的频率和结果。方法所有的HBV monoinfected病人11大欧洲中心（维吉尔研究组）治疗恩替卡韦进行了研究。耀斑被定义为ALT水平>3×基线相比，具有绝对的ALT水平>3×ULN。结果733例患者接受治疗的168（IQR84-213）周恩替卡韦单药治疗的中位数。 19例（3％）开发的耀斑的26（10-83）周中位数之后。没有患者制定基因型耐药性和唯一一例违规被记录在案。耀斑是相对温和，为7.3×ULN（IQR4.5-10-1）中位数ALT高峰。在患者发作，人们开发了HBeAg血清学转换，以及一个HBeAg消失。基线HBeAg状态（HR =2.91，95％CI为1.17-7.23，P =0.02），HBV-DNA（HR =1.31，95％CI为1.06-1.63，P=0.01），血小板计数（HR =1.0，95％CI为0.98〜1.00， P = 0.04），白蛋白（HR =0.91，95％CI为0.84-0.99，P=0.03）均与耀斑的发展。九名病人（47％）HBV-DNA，3例（16％），具有稳定的HBV DNA和七（37％）与增加血清HBV DNA下降过程中进行了火炬。 10周（IQR4-21），这是显著同期相比于耀斑中位数后发生过程中HBV DNA的稳定或上升过程中HBV DNA水平下降耀斑（76周，IQR29-149）（P <0.001） 。恩替卡韦期间结论耀斑是罕见的。治疗26周前发生的耀斑在患者的HBV DNA持续下跌过程中几乎完全存在。在这些患者ETV可以在严格的监控将继续为广大有很好的biochemical-和病毒学结果。

披露：

伊万娜·凯里 - 格兰特/研究支持：Gilead公司，拜耳，罗氏公司;口语和教学：BMS

阿什利·布恩 - 咨询委员会或审查小组：默沙东，罗氏，的Bris-TOL-迈尔斯施贵宝，吉利德，扬森，Abbvie，艾琪尔顿;口语和教学：默沙东，罗氏，施贵宝，吉利德，扬森，Abbvie

约尔格·彼得森 - 咨询委员会或审查小组：百时美施贵宝，Gilead公司，诺华，默克，施贵宝，Gilead公司，诺华，默克公司;格兰特/研究支持：罗氏，葛兰素史克，罗氏，葛兰素史克公司;口语和教学：雅培，Tibotec公司，默克，雅培，Tibotec公司，默克公司

弗洛里安·范博梅尔 - 咨询委员会或审查小组：吉利德科学公司，罗氏制药;格兰特/研究支援：Biopredictive;口语和教学：施贵宝，杨森，罗氏制药，吉利德科学公司

罗伯特·德Knegt - 咨询委员会或审查小组：默沙东，罗氏，Norgine，扬森Cilag公司;格兰特/研究支持：Gilead公司，默沙东，罗氏，杨森Cilag公司，拜耳;口语和教学：Gilead公司，默沙东，罗氏，杨森Cilag公司

Jurrien G. Reijnders - 咨询：基列;口语和教学：布里斯托尔迈尔斯 - 施贵宝

托马斯·贝格 - 咨询委员会或审查小组：Gilead公司，拜耳，罗氏，Tibotec公司，顶点，Jannsen，诺华，雅培，默克公司;咨询：Gilead公司，拜耳，罗氏，Tibotec公司;顶点，扬森;格兰特/研究支持：Gilead公司，拜耳，罗氏，Tibotec公司;顶点，Jannssen，默克/默沙东，勃林格殷格翰，诺华公司;口语和教学：Gilead公司，拜耳，罗氏，Tibotec公司;顶点，扬森，默克/默沙东，诺华，默克，拜耳

塔尼亚米威尔兹尔 - 咨询委员会或审查小组：诺华，西安杨森，基列，Abbvie，勃林格殷格翰+

斯特凡Zeuzem - 咨询：Abbvie，勃林格殷格翰，百时美施贵宝公司，Gilead公司，诺华制药公司，默克公司，Idenix公司，西安杨森，罗氏制药公司，Vertex制药公司

海纳魏德迈 - 咨询委员会或审查小组：转基因，MSD

罗氏公司，Gilead公司，雅培，拜耳，福尔克，Abbvie，诺华，葛兰素史克;格兰特/研究

技术支持：默沙东，诺华，Gilead公司，罗氏，雅培;口语和教学：BMS，

默沙东，诺华，创新及科技基金，Abbvie，吉利德

玛丽亚·布提 - 咨询委员会或审查小组：Gilead公司，西安杨森，顶点，MSD;格兰特/研究支持：Gilead公司，扬森;口语和教学：Gilead公司，西安杨森，顶点，诺华

法比安Zoulim - 咨询委员会或审查小组：扬森，基列，Novira，Abbvie，Tykmera，转基因;咨询：罗氏;格兰特/研究支持：诺华，基列，Scynexis，罗氏，Novira;口语和教学：施贵宝公司，吉利德

哈里L.詹森 - 咨询：雅培，施贵宝公司，德彪，Gilead Sciences公司，默克公司，美敦力公司，诺华，罗氏，Santaris;格兰特/研究支持：Anadys公司，施贵宝公司，Gilead科学，Innogenetics公司，麒麟，默克公司，美敦力公司，诺华，罗氏，Santaris

下面的人都没有透露：宝莲ARENDS，恒智，马西莫·法萨诺，戴维·J·Mutimer，卡佳Deterding，叶H·吴，邓丽君Santantonio，皮埃尔Pradat，贝蒂娜汉森