AASLD2014:肝脏硬度和肝纤维化活动 2年恩替卡韦的影响2年恩替

StephenW

1922
2-years impact of entecavir (ETV) on liver fibrosis and activity as assessed by FibroTest – ActiTest and Liver Stiffness Measurement (LSM) in chronic hepatitis B (CHB) patients
Fabien Zoulim1, Xavier Causse2, Vincent Leroy3, Denis Ouzan4, Nathalie Ganne-Carrie5, Valerie Bourcier5, Victor de Ledinghen6, Philippe Mathurin7, Marika Rudler8, Joseph Moussalli8, Dominique Thabut8, Luminita Bonyhay8, Vlad Ratziu8, Fabienne Drane9, Yen Ngo9, Mona Munteanu9, Thierry Poynard8;
1Hepatology, Hospices Civils, Lyon, France; 2Hepatology, CHR ORLEANS, ORLEANS, France; 3Hepatology, CHU Grenoble, Grenoble, France; 4Hepatology, Institut Arnault Tzanck, St Laurent du Var, France; 5Hepatology, Jean Verdier Hospital, BONDY, France; 6Hepatology, CHU Bordeaux, Bordeaux, France; 7Hepatology, CHRU Lille, LILLE, France; 8Hepatology, APHP UPMC Liver Center Pitié Salpêtrière Hospital, PARIS, France; 9Hepatology Research Unit, BioPredictive, PARIS, France
Background. Fibrosis-regression(FR) rate in treated CHB-patients patients was similary estimated using Fibrotest and LSM (Fibros-can), although with possible overestimation of FR by LSM related to necroinflammatory activity(NIA).(AntivirTher2009,2010)


Aims. To prospectively evaluate : 1)The histological impact of strong inhibitor of HBV-replication, entecavir-motherapy [0.5mg/day], using Fibrotest-Actitest and LSM.2) The impact of presumed steatosis(Steatotest) on the treatment response.


Methods. NUC-naïve CHB preincluded [19-centers,France] fol-lowed-up (FU) from baseline to M6,M12 and M24-months. Viral-response(VR) defined as undetectable-HBVDNA.

Results. N=177 pre-included, 15-retracted, 3-died, 5 non-applicable Fibrotest (4 flare-up ALT>600IU/L), 24 lost-of-follow-up (FU); N=137 with M6-FU included [age 45(20-83)yrs; 71%males; 84% anti-HBe(+); 43%caucasian/29%asian/28%african]. Applicable-LSM vs Fibrotest 95%vs97.2%(p<0.0001). Fibro- test presumed advanced fibrosis(AF,F2F3F4-METAVIR) in 36%(60/167) and cirrhosis 12%(N=20/167); presumed NIA (Actitest) in 74%(123/166) and baseline steatosis>1% (Steatotest) 37%(57/156). N=43 had liver biospy [size 24(5-40)] AF 56%(24/43). VR prevalences were 67% M6(N=120), 83% M12(N=105) and 86%M24(N=50). Presumed NIA [Actitest] regressed from M0 0.38(0.02) to M6 0.21(0.01), M12 0.19(0.01) and M24 0.14(0.02), all p<0.0001vsM0. 76% patients with baseline-NIA regressed at M6. Presumed AF [Fibrotest] regressed from M0 0.69(0.02) vs M6 0.59(0.03) vs M12 0.57(0.03), M24 0.60(0.04), all p<0.01vsM0. M12-FR patients had lower prevalece of baseline steatosis>5% (Steatotest) than those without: 40%vs8%,p=0.003. FR using LSM from baseline to M6 (NS) and to M12 [N=23; 8.6(4.2) vs6.2(0.4)kPa,P=0.001)]. Regardless VR, M12 AF-prevalences decreased [39%vs30%,p=NS]; M12-VR had lower remaining NIA versus non-VR (17%vs56%,p=0.01).


Conclusion. Twelve months entecavir, reduced significantly AF and NIA presumed by Fibrotest-Actitest and LSM, regardless of the viral response. Patients without M12-FR had more baseline steatosis presumed by Steatotest.

Disclosures:
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
Xavier Causse - Board Membership: Gilead, Janssen-Cilag; Grant/Research Support: Roche; Speaking and Teaching: Gilead, BMS, Janssen-Cilag
Vincent Leroy - Board Membership: roche, merck, gilead, bms, roche, merck, gilead, bms, roche, merck, gilead, bms, roche, merck, gilead, bms; Consulting: jansen, jansen, jansen, jansen; Grant/Research Support: roche, gilead, bms, roche, gilead, bms, roche, gilead, bms, roche, gilead, bms; Speaking and Teaching: bms, merck, gilead, roche, bms, merck, gilead, roche, bms, merck, gilead, roche, bms, merck, gilead, roche
Nathalie Ganne-Carrie - Advisory Committees or Review Panels: Roche, Bayer; Speaking and Teaching: BMS, Gilead
Victor de Ledinghen - Advisory Committees or Review Panels: Merck, Janssen, Gilead, BMS, Abbvie; Grant/Research Support: Gilead, Janssen; Speaking and
Teaching: AbbVie, BMS
Philippe Mathurin - Board Membership: Schering-Plough, Janssen-Cilag, BMS, Gilead, Abvie; Consulting: Roche, Bayer, Boehringer
Marika Rudler - Speaking and Teaching: Gilead
Joseph Moussalli - Consulting: merck, roche, gilead
Vlad Ratziu - Advisory Committees or Review Panels: GalMed, Abbott, Genfit, Enterome, Gilead; Consulting: Astellas, Axcan, Pfizer, Sanofi-Synthelabo, Genen-tech, Nycomed
Fabienne Drane - Employment: BIOPREDICTIVE
Yen Ngo - Employment: BioPredictive Mona Munteanu - Employment: Biopredictive
Thierry Poynard - Advisory Committees or Review Panels: Merck; Speaking and Teaching: BMS; Stock Shareholder: Biopredictive
The following people have nothing to disclose: Denis Ouzan, Valerie Bourcier, Dominique Thabut, Luminita Bonyhay

StephenW

1922
ActiTest和肝脏硬度测量（LSM）的慢性乙型肝炎（CHB）患者 - 作为评估FibroTest的肝纤维化和活动2年恩替卡韦的影响（ETV）
小煜Zoulim1，泽维尔Causse2，文森特Leroy3，丹尼斯Ouzan4，娜塔莉Ganne-Carrie5，瓦莱丽Bourcier5，维克多德Ledinghen6，菲利普Mathurin7，玛丽卡Rudler8，约瑟夫Moussalli8，多米尼克Thabut8，Luminita Bonyhay8，弗拉德Ratziu8，法比耶纳Drane9，颜Ngo9，蒙娜丽莎Munteanu9蒂埃里Poynard8;
1Hepatology，收容所Civils，法国里昂; 2Hepatology，CHR新奥尔良，新奥尔良，法国的; 3Hepatology，朱格勒诺布尔，法国格勒诺布尔; 4Hepatology，研究所阿尔诺Tzanck，圣洛朗杜瓦尔，法国; 5Hepatology，让迭尔医院，BONDY，法国; 6Hepatology，朱波尔多，波尔多，法国; 7Hepatology，CHRU里尔，里尔，法国; 8Hepatology，APHP UPMC肝病中心Pitié妇女救济院医院，法国巴黎; 9Hepatology研究单位，BioPredictive，巴黎，法国

背景。肝纤维化回归（FR）率在慢性乙肝治疗的住院病人患者是类似地FibroTest的使用和LSM（Fibros-CAN）估计，尽管FR通过LSM与坏死性炎症（NIA）的可能的高估。（AntivirTher2009,2010）的目标。前瞻性评估：1）HBV复制，恩替卡韦motherapy[0.5毫克/天]，FibroTest的使用，Actitest和LSM.2）推测脂肪变性（Steatotest）对治疗反应的影响的强抑制剂的组织学的影响。方法。 NUC初治慢性乙肝preincluded[19-中心，法国] FOL-lowed式（FU）从基线到M6，M12和M24-个月。病毒应答（VR）定义为检测不到，HBVDNA。结果。 N =177预先在内，15缩回，3-死亡，5不适用FibroTest的（4-火炬式ALT>600IU/ L）24失的，后续（FU）; N =137，使用M6-FU包括[年龄45（20-83）岁; 71％的男性; 84％的抗HBe（+）; 43％的白种人/29％亚洲/28％的非洲。适用-VS LSM FibroTest的95％vs97.2％（P <0.0001）。成纤维检验假设肝纤维化（AF，F2F3F4-METAVIR）的36％（60/167），肝硬化12％（N= 20/167页）;假定NIA（Actitest）的74％（166分之123）和基线脂肪肝>1％（Steatotest），37％（57/156）。 N =43有肝biospy[尺寸24（5-40）] AF56％（24/43）。 VR患病率分别为67％M6（N=120），83％的M12（N=105）和86％的M24（N =50）。假定NIA[Actitest]从M00.38（0.02）回归到M60.21（0.01），M120.19（0.01）和M240.14（0.02），P均<0.0001vsM0。 76％的患者基线NIA在倒退M6。假定AF[FibroTest的]从M00.69（0.02）回归VS M60.59（0.03）与M120.57（0.03），M240.60（0.04），P均<0.01vsM0。 M12-FR患者基线脂肪>5％（Steatotest）比没有更低prevalece：40％VS8％，p值= 0.003。 FR采用LSM从基线到M6（NS）及M12[N=23; 8.6（4.2）vs6.2（0.4）千帕，P = 0.001）。无论VR，M12 AF-患病率下降[39％VS30％，P= NS] M12-VR具有较低剩余NIA与非VR（17％vs56％，p值= 0.01）。结论。十二个月恩替卡韦，降低显著AF和NIA通过FibroTest的-Actitest和LSM推测，无论病毒反应。患者无M12-FR有更多的脂肪基线由Steatotest推测。

披露：

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：布里斯托尔Myers Squibb公司，吉利德

泽维尔喀斯 - 董事会成员：Gilead公司，杨森 -  Cilag公司;格兰特/研究支持：罗氏公司;说起与教学：Gilead公司，BMS，杨森 -  Cilag公司

文森特·勒鲁瓦 - 董事会成员：罗氏，默克，吉利德，拜耳，罗氏，默克，吉利德，拜耳，罗氏，默克，吉利德，拜耳，罗氏，默克，吉利德，BMS;咨询：扬森，扬森，扬森，扬森;格兰特/研究支持：罗氏公司，Gilead公司，BMS，罗氏公司，Gilead公司，BMS，罗氏公司，Gilead公司，BMS，罗氏，吉利德，BMS;说起与教学：BMS，默克，吉利德，罗氏，拜耳，默克，吉利德，罗氏，拜耳，默克，吉利德，罗氏，拜耳，默克，吉利德，罗氏

娜塔莉Ganne - 凯莉 - 咨询委员会或审查小组：罗氏，拜耳;说起与教学：BMS，吉利德

维克多·德Ledinghen - 咨询委员会或审查小组：默克，杨森，基列，BMS，Abbvie;格兰特/研究支持：Gilead公司，扬森;说起和

教学：AbbVie，BMS

菲利普·马图林 - 董事会成员：先灵葆雅，扬森 -  Cilag公司，BMS，基列，Abvie;咨询：罗氏，拜耳，勃林格

玛丽卡Rudler - 口语与教学：吉利德

约瑟夫·穆萨利 - 咨询：默克，罗氏，吉利德

弗拉德Ratziu - 咨询委员会或审查小组：GalMed，雅培，Genfit，Enterome，基列;咨询：安斯泰来，AXCAN，辉瑞，赛诺菲 - 合成，Genen高科技，奈科明

法比耶纳Drane - 就业：BIOPREDICTIVE

颜鹤 - 就业：BioPredictive蒙娜丽莎蒙特亚努 - 就业：Biopredictive

蒂埃里Poynard - 咨询委员会或审查小组：默克公司;说起与教学：BMS;股股东：Biopredictive

下面的人都没有透露：丹尼斯Ouzan，瓦莱丽Bourcier，多米尼克Thabut，Luminita Bonyhay