AASLD2014:恩替卡韦的安全性和有效性的慢性乙型肝炎患者在美

StephenW

1871Entecavir Safety and Effectiveness in a National Cohort of Chronic Hepatitis B Patients in the United States - the ENUMERATE studyJoseph Ahn1, Hannah Lee2, Joseph K. Lim3, Calvin Q. Pan4, Mindie H. Nguyen5, W. Ray Kim5, Huy N. Trinh6, Tram T. Tran7, Danny Chu8, Albert Min9, Son T. Do10, Jocelyn Woog11, Ajitha Mannalithara5, Anna S. Lok12;1OHSU, Portland, OR; 2Tufts Medical Center, Boston, MA; 3Yale University, New Haven, CT; 4NYU Langone, New York City, NY; 5Stanford University, Stanford, CA; 6San Jose Gastroenterology, San Jose, CA; 7Cedars-Sinai, Los Angeles, CA; 8Albert Einstein College of Medicine, New York City, NY; 9Mount Sinai Beth Israel, New York City, NY; 10Digestive Health Associates of Texas, Plano, TX; 11Asian Health Foundation, Rochester, MN; 12University of Michigan, Ann Arbor, MIBackground- Entecavir (ETV) has been shown to be safe and efficacious in randomized controlled trials in highly selected patients infected with hepatitis B virus (HBV). There are limited data about the safety and effectiveness of ETV in “real-life” patients in the US. Aim- To determine the safety and effectiveness of ETV in “real-life” patients with HBV infection in the US. Methods- The ENUMERATE study was conducted in a national network of 26 academic and private liver centers in the US, in partnership with the AHF. Treatment-naTve HBV patients ≥ 18 years old who received ETV for ≥ 12 months between 2005 and 2013 were included. Exclusion criteria included co-infection with HIV, hepatitis C or D, a history of hepatocellular carcinoma (HCC) or solid organ transplantation. Outcome measures included cumulative rates of ALT normalization, unde-tectable HBV DNA level, HBeAg and HBsAg loss/seroconversion, estimated glomerular filtration rate (GFR) based on the MDRD formula, and adverse events (AE) leading to ETV dose reduction or discontinuation. Results- Of 841 patients, 745 [63% male, 83% Asian; median age 47 (18-83) years] met the inclusion criteria. At baseline, 195 (26%) were HBeAg+ and 69 (9.3%) had cirrhosis. Abnormal ALT (ALT ≥ 30 U/L for men, ≥ 19 U/L for women) was observed in 89% of patients, with a median of 58 (6-3286) U/L. Baseline median HBV DNA was 5.7 log 10 (1.9-10.2) IU/ml. Median duration of ETV treatment was 4 (1-8.3) years. Among all patients tested for ALT, 42.1% (308/731) had normal ALT at year 1, 46.8% (251/536) at year 3, and 53.3% (169/317) at year 5. At year 1, 63% (308/489) had undetectable HBV DNA, 76.3% (222/291) at year 3, and 82.4% (126/153) at year 5. At 5 years, cumulative probability of HBeAg loss and HBeAg seroconversion was 38.5% and 29.7%, respectively and of HBsAg l oss was 4.4%. Median GFR was 92.6 (IQR 79, 107.2) ml/min at baseline and 91.9 (IQR 79.9, 106.4) mL/min at 5 years. ETV dose reduction was required in 2 patients due to renal insufficiency. ETV discontinuation was required in 7 patients due to AEs with two for nonfatal lactic acidosis. Hepatic decompensation occurred in 10 patients (1.3%) and HCC in 26 (3.5%) patients. Seven patients died (3 liver related). Conclusion- In a large “real-life” US cohort of HBV-infected patients, ETV treatment was well tolerated. Rates of ALT normalization, HBV DNA suppression, and HBeAg seroconversion were lower than those previously reported in randomized clinical trials.
Disclosures:
Joseph Ahn - Advisory Committees or Review Panels: gilead; Grant/Research Support: bms
Hannah Lee - Grant/Research Support: BMS
Joseph K. Lim - Consulting: Merck, Vertex, Gilead, Bristol Myers Squibb, Boeh-ringer-Ingelheim; Grant/Research Support: Abbott, Boehringer-Ingelheim, Bristol Myers Squibb, Genentech, Gilead, Janssen/Tibotec, Vertex, Achillion
Calvin Q. Pan - Advisory Committees or Review Panels: BMS, Gilead; Consulting: BMS, Gilead, Merck, Abbvie, Janssen ; Grant/Research Support: BMS, Gilead, Genentech, Merck; Speaking and Teaching: BMS, Gilead, Onyx
Mindie H. Nguyen - Advisory Committees or Review Panels: Bristol-Myers Squibb, Bayer AG, Gilead, Novartis, Onyx; Consulting: Gilead Sciences, Inc.; Grant/Research Support: Gilead Sciences, Inc., Bristol-Myers Squibb, Novartis Pharmaceuticals, Roche Pharma AG, Idenix, Hologic, ISIS
W. Ray Kim - Consulting: Bristol Myers Squibb, Gilead Sciences
Huy N. Trinh - Advisory Committees or Review Panels: BMS, Gilead; Grant/ Research Support: BMS, Gilead; Speaking and Teaching: BMS, Gilead, vertex; Stock Shareholder: Gilead
Tram T. Tran - Advisory Committees or Review Panels: Gilead, Bristol Myers Squibb; Consulting: Gilead, AbbVie, Janssen; Grant/Research Support: Bristol Myers Squibb; Speaking and Teaching: Bristol Myers Squibb, Gilead
Danny Chu - Consulting: Gilead, Gilead, Gilead, Gilead; Speaking and Teaching: Gilead, Gilead, Gilead, Gilead
Albert Min - Consulting: Bristol Myers Squibb, Gilead, Janssen; Grant/Research Support: Bristol Myers Squibb, Gilead; Speaking and Teaching: Bristol Myers Squibb, Gilead
Son T. Do - Advisory Committees or Review Panels: gilead, Asian Health Foundation, gilead, Asian Health Foundation, gilead, Asian Health Foundation, gilead, Asian Health Foundation; Speaking and Teaching: bms, gilead, Asian Health Foundation, bms, gilead, Asian Health Foundation, bms, gilead, Asian Health Foundation, bms, gilead, Asian Health Foundation
Anna S. Lok - Advisory Committees or Review Panels: Gilead, Immune Targeting System, MedImmune, Arrowhead, Bayer, GSK, Janssen, Novartis, ISIS, Tekmira; Grant/Research Support: Abbott, BMS, Gilead, Merck, Roche, Boehringer
The following people have nothing to disclose: Jocelyn Woog, Ajitha Manna-lithara

StephenW

1871
恩替卡韦的安全性和有效性的慢性乙型肝炎患者在美国国家队列 - 中列举的研究
约瑟夫Ahn1，汉娜Lee2，约瑟夫·K。Lim3，卡尔文问：Pan4，Mindie阁下Nguyen5，W雷Kim5，伊北Trinh6，电车吨Tran7，丹尼Chu8，阿尔伯特Min9，儿子吨DO10，乔斯林Woog11， Ajitha Mannalithara5，安娜·S。Lok12;
1OHSU，波特兰，俄勒冈; 2Tufts医学中心，波士顿，MA; 3Yale大学，纽黑文，CT; 4NYU朗格尼，纽约市，纽约州; 5Stanford大学，斯坦福大学，加州; 6San何塞消化内科，圣何塞，加利福尼亚; 7Cedars - 西奈，洛杉矶，加州; 8Albert爱因斯坦医学院，纽约市，纽约州; 9Mount西奈贝斯以色列，纽约市，纽约州;德克萨斯州普莱诺，德克萨斯州10Digestive卫生协会; 11Asian健康基金会，明尼苏达州罗切斯特; 12University密歇根州，密歇根州安阿伯

背景 - 恩替卡韦（ETV）已被证明是安全和有效的在感染乙肝病毒（HBV）高度选择的患者的随机对照试验。有关于教育电视的“现实生活”的病人，在美国的安全性和有效性的数据有限。 Aim-要确定在“现实生活”患者乙肝病毒感染在美国的教育电视的安全性和有效性。方法 - 本研究列举了在美国26学术界和私营肝脏中心的全国性网络进行的，与AHF的合作伙伴关系。治疗naTve乙肝患者≥18岁的谁2005至2013年间接受恩替卡韦用于≥12个月都包括在内。排除标准包括混合感染了艾滋病毒，丙型肝炎或D，肝细胞癌（HCC）或实体器官移植的历史。观察指标包括ALT复常，UNDE-tectable的HBV DNA水平，HBeAg和HBsAg消失/血清学转换的基础上，MDRD公式估算的肾小球滤过率（GFR），以及不良事件（AE），导致ETV减少剂量或停药的累计利率。结果 - 841例，745[63％为男性，83％亚裔;中位年龄47（18-83）岁符合纳入标准。基线，195（26％）为HBeAg+和69（9.3％）有肝硬化。 ALT异常（ALT≥30 U / L，男性，≥19 U / L，女），观察患者的89％，其中58（6-3286）中位数U / L。基线HBV DNA中位数为5.7日志10（1.9-10.2）国际单位/毫升。恩替卡韦治疗时间的中位数为4（1-8.3岁）。在测试的ALT所有患者，42.1％（731分之308）的ALT正常的1年，46.8％（536分之251）在第3年和53.3％（三百一十七分之一百六十九）在今年5于1年，63％ （四百八十九分之三百零八）检测不到HBV DNA，76.3％（291分之222）在第3年和82.4％（一百五十三分之一百二十六）在今年55年时，HBeAg阴转和HBeAg血清学转换的累积概率为38.5％和29.7 ％，分别为乙肝表面抗原升OSS和4.4％。肾小球滤过率中位数为92.6（IQR为79，107.2）ml / min的基线和91.9（IQR为79.9，106.4）mL / min的5年。被要求在2例患者ETV剂量减少因肾功能不全。恩替卡韦停药被要求在7例患者因不良事件有两个非致死性乳酸性酸中毒。肝功能失代偿发生10例（1.3％）和肝癌26例（3.5％）的患者。七例死亡（3肝有关）。结论 - 在一个大的“现实生活”美HBV感染患者的队列中，恩替卡韦治疗的耐受性良好。 ALT复常，HBV-DNA抑制，HBeAg血清学转换的比例显着高于先前的随机临床试验报告为低。

披露：

约瑟夫·安 - 咨询委员会或审查小组：基列;格兰特/研究支援：BMS

汉娜李 - 格兰特/研究支持：BMS

约瑟夫·K.林 - 咨询：默克，顶点，基列，施贵宝公司，Boeh-铃声殷格翰;格兰特/研究支持：雅培，勃林格殷格翰，施贵宝公司，基因泰克，Gilead公司，扬森/ Tibotec公司，顶点，艾琪尔顿

卡尔文问：泛 - 咨询委员会或审查小组：BMS，基列;咨询：BMS，Gilead公司，默克公司，Abbvie，扬森;格兰特/研究支持：BMS，Gilead公司，基因泰克，默沙东;口语和教学：BMS，基列，玛瑙

Mindie H.阮 - 咨询委员会或审查小组：百时美施贵宝，拜耳公司，Gilead公司，诺华公司，玛瑙;咨询：吉利德科学公司;格兰特/研究支持：吉利德科学公司，施贵宝，诺华制药，罗氏制药公司Idenix公司，Hologic公司，ISIS

W·雷金 - 咨询：施贵宝公司，Gilead科学

伊北郑氏 - 咨询委员会或审查小组：BMS，基列;格兰特/研究支持：BMS，基列;口语和教学：BMS，基列，顶点;股股东：吉利德

电车T.陈德良 - 咨询委员会或审查小组：Gilead公司，施贵宝公司;咨询：基列，AbbVie，扬森;格兰特/研究支援：施贵宝公司;口语和教学：施贵宝公司，吉利德

朱丹尼 - 咨询：基列，基列，基列，基列;口语和教学：Gilead公司，Gilead公司，Gilead公司，吉利德

阿尔伯特最小 - 咨询：施贵宝公司，Gilead公司，扬森;格兰特/研究支援：施贵宝公司，Gilead公司;口语和教学：施贵宝公司，吉利德

儿子T.执行 - 咨询委员会或审查小组：Gilead公司，亚洲健康基金会，基列，亚洲健康基金会，基列，亚洲健康基金会，基列，亚洲健康基金会;口语和教学：BMS，基列，亚洲健康基金会，拜耳，基列，亚洲健康基金会，拜耳，基列，亚洲健康基金会，拜耳，基列，亚洲健康基金会

安娜南乐 - 咨询委员会或审查小组：基列，免疫瞄准系统，MedImmune公司，慈姑，拜耳，葛兰素史克，西安杨森，诺华，ISIS，Tekmira;格兰特/研究支持：雅培，拜耳，基列，默克，罗氏，勃林格

下面的人都没有透露：乔斯林Woog，Ajitha甘露，lithara

咬牙硬挺

算是好消息，帮助患者坚持住不倒下，就是立于不败之地了。

xiazhifeng0009

怎么说！ 55年？转换？