AASLD2014:乙肝核心相关抗原水平关联到响应的ETV和PEG-IFN治疗HBe

StephenW

1868Hepatitis B Core Related Antigen Levels Are Associated With Response To ETV and PEG-IFN Treatment In HBeAg-Positive Chronic Hepatitis B PatientsWillem Pieter Brouwer1, Milan J. Sonneveld1, Qing Xie2, Qing Zhang3, Fehmi Tabak4, Adrian Streinu-cercel5, Jiyao Wang6, Gertine van Oord1, Thomas Vanwolleghem1, Suzan D. Pas7, Robert J. de Knegt1, Andre Boonstra1, Bettina E. Hansen1,8, Harry L. Janssen9,1;1Gastroenterology & Hepatology, Erasmus Medical Center Rotterdam, Rotterdam, Netherlands; 2Infectious Diseases, Ruijin Hospital, Jiaotong University, Shanghai, China; 3Gastroenterology and Hepatology, Shanghai Public Health Center, Fu Dan University, Shanghai, China; 4Cerrahpasa Medical Faculty, Istanbul, Turkey; 5National Institute of Infectious Disease, Bucharest, Romania; 6Gastroenterology and Hepatology, Zhong Shan Hospital, Fu Dan University, Shanghai, China; 7Viroscience, Erasmus Medical Center Rotterdam, Rotterdam, Netherlands; 8Department of Public Health, Erasmus MC University Medical Center, Rotterdam, Netherlands; 9Toronto Center for Liver Disease, Toronto Western and General Hospital, University Health Network, Toronto, ON, CanadaBackground. Hepatitis B core related antigen (HBcrAg) is a new marker which is a combined measure of the core proteins HBeAg, HBcAg and p22cr, and correlates with intrahe-patic covalently closed circular DNA. Serum HBcrAg levels may therefore be associated with response to antiviral therapy. Methods. We studied HBeAg-positive patients treated within an international randomized trial (ARES), in which all patients were treated with ETV (0.5mg/day) from w0-24, and randomized to either PEG-IFN add-on from w24-48 (n=85), or to ETV-monotherapy continuation (n=90). Response was defined as HBeAg-loss with HBV DNA<200IU/ml. Only responders at w48 stopped ETV at w72. All patients were followed until w96. Serum HBcrAg was measured using the Lumipulse® G HBcrAg (Fujirebio Europe). Results. At w96, response was achieved in 31% vs. 20% of patients assigned PEG-IFN add-on vs. monotherapy respectively. Lower HBcrAg levels at w0 were associated with response to ETV (OR 0.5, 95%CI:0.3-0.8, p<0.001), but not to PEG-IFN add-on (OR 0.9, 95%CI:0.5-1.6, p=0.678). At w96 more HBcrAg decline was observed among responders (−2.6 vs -2.0 log U/mL for monotherapy and −3.5 vs −2.0 log U/mL for add-on, both p<0.001), with more decline for responders to add-on vs. monotherapy (p=0.010; figure). Lower HBcrAg levels at w48 were associated with HBsAg levels <1000IU/mL at w96 (OR 0.5, 95%CI:0.3-0.8, p=0.002). By Bland-Altman analysis, agreement between HBeAg and HBcrAg measurements at w0 was close (mean difference -3.1×10-6 Log U/mL, 95%CI:-0.9 - 0.9), with comparable on-treatment results obtained for w12-96. Conclusion. On-treatment HBcrAg decline is associated with response to both ETV monotherapy and ETV+PEG-IFN add-on therapy, with most prominent declines observed during PEG-IFN. HBcrAg and HBeAg measurements seemed to follow similar on-treatment dynamics.

Disclosures:
Milan J. Sonneveld - Advisory Committees or Review Panels: Roche; Speaking and Teaching: Roche, BMS
Suzan D. Pas - Grant/Research Support: the Virgo consortium, funded by the Dutch government (FES0908), the Netherlands Genomics Initiative (NGI) project number 050-060-452, the European Community Seventh Framework Programme (FP7/2007-2013) under project EMPERIE (grant agreement no. 223498]
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
Andre Boonstra - Grant/Research Support: BMS, Janssen Pharmaceutics, Merck, Roche
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: Willem Pieter Brouwer, Qing Xie, Qing Zhang, Fehmi Tabak, Adrian Streinu-cercel, Jiyao Wang, Gertine van Oord, Thomas Vanwolleghem, Bettina E. Hansen

StephenW

1868
乙肝核心相关抗原水平关联到响应的ETV和PEG-IFN治疗HBeAg阳性慢性乙型肝炎患者
威廉·彼得·Brouwer1，米兰J. Sonneveld1，清Xie2，清Zhang3，Fehmi Tabak4，阿德里安Streinu-cercel5，唐继尧Wang6，Gertine面包车Oord1，托马斯Vanwolleghem1，苏珊D. PAS7，罗伯特·德Knegt1，安德烈Boonstra1，贝蒂娜E。 Hansen1,8，哈利属Janssen9,1;
1Gastroenterology及肝脏，Erasmus医学中心鹿特丹，荷兰鹿特丹; 2Infectious疾病，瑞金医院，上海交通大学，中国; 3Gastroenterology和肝病，上海公共卫生中心，复旦大学，上海，中国; 4Cerrahpasa医学院，土耳其伊斯坦布尔;传染病，布加勒斯特，罗马尼亚5National研究所; 6Gastroenterology和肝病中山医院，复旦大学，上海，中国; 7Viroscience，Erasmus医学中心鹿特丹，荷兰鹿特丹; 8Department公共卫生，伊拉斯谟的MC大学医学中心，鹿特丹，荷兰; 9Toronto中心肝病，多伦多西部和综合医院，大学健康网络，多伦多，加拿大

背景。乙型肝炎核心相关抗原（HBcrAg）是一个新的标志这是核心蛋白的HBeAg，HBcAg的p22cr的组合措施，并且与intrahe-patic共价闭合环状DNA。血清HBcrAg水平因此可以与响应于抗病毒疗法相关联。方法。我们研究HBeAg阳性患者的国际随机试验（ARES），在其中所有患者均从w0-24治疗ETV（0.5毫克/天）内的处理，并随机分配至PEG-IFN附加从w24-48（ N =85），或恩替卡韦，继续单药治疗组（n =90）。反应定义为HBeAg的损失与HBV DNA<200IU/毫升。在W48仅反应停ETV在W72。所有患者均随访至W96。使用Lumipulse®ģHBcrAg（Fujirebio公司欧洲）血清HBcrAg测定。结果。在W96，反应在31％达到了与患者的20％PEG-IFN加上与单一疗法分别被分配。下HBcrAg水平W0分别与应对教育电视（或0.5，95％CI：0.3〜0.8，P<0.001），而不是PEG-IFN附加（或0.9，95％CI：0.5-1.6，P =0.678）。在W96更HBcrAg跌幅一度反应中观察到（-2.6与-2.0登录U / ml的单药治疗和-3.5-2.0与记录单位/毫升的加载项，均P <0.001），与更多的跌势响应者ADD-在与单药治疗（P = 0.010;图）。下HBcrAg水平W48均与HBsAg水平<1000IU/毫升，在W96（或0.5，95％CI：0.3〜0.8，P = 0.002）。由奥特曼分析，在W0 HBeAg和HBcrAg测量之间的协议接近（平均差-3.1×10-6日志单位/毫升，95％CI：-0.9 - 0.9），具有可比性的处理结果w12-获得96。结论。在处理HBcrAg下降与响应这两个ETV单药治疗和恩替卡韦+ PEG-IFN相关的附加治疗，大多数在PEG-IFN观察到显着的下降。 HBcrAg和HBeAg的测量似乎遵循类似的处理力度。
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披露：

米兰J. Sonneveld - 咨询委员会或审查小组：罗氏公司;口语和教学：罗氏，拜耳

苏珊D. PAS - 格兰特/研究支持：处女座的财团，由荷兰政府（FES0908）资助，荷兰基因组计划（NGI）项目编号050-060-452，欧盟第七框架计划（FP7/2007-2013 ）根据项目EMPERIE（赠款协议没有。223498]

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

安德烈Boonstra - 格兰特/研究支持：拜耳，西安杨森制药，默克，罗氏

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：威廉·彼得·布劳威尔，清泄，张青，Fehmi塔巴克，阿德里安Streinu-cercel，基尧王，Gertine面包车Oord公司，托马斯Vanwolleghem，贝蒂娜汉森