EASL 2013 十二个​​月恩替肝纤维化的变化

StephenW

Abstract 765
     
TWELVE-MONTHS ENTECAVIR LONGITUDINAL CHANGES IN LIVER FIBROSIS, ACTIVITY AS PER FIBROTEST-FIBROMAX AND LIVER STIFFNESS MEASUREMENTS IN CHRONIC HEPATITIS B. STEATOSIS IMPACT ON FIBROSIS REGRESSION   

F. Zoulim1, X. Causse2, V. Leroy3, D. Ouzan4, N. Ganne5, V. Bourcier5, V. de Ledinghen6, P. Mathurin7, J. Moussalli8, M. Rudler8, L. Bonyhay8, D. Thabut8, R. Pais8, J. Massard8, V. Di Martino9, F. Dranne10, C. Renou11, J.-P. Bronowicki12, Y. Ngo10, M. Munteanu10*, T. Poynard8, ENTEFIB Group
1Hospices Civils de Lyon, Lyon, 2CHR Orleans La Source, Orléans, 3CHU de Grenoble, Grenoble, 4Institut Arnaud Tzanck, France, 5Hôpital Jean Verdier, Bondy, 6Hôpital Haut-Lévêque, Bordeaux, 7CHU Lille, Lille, 8UPMC APHP Liver Center, GH Pitié Salpêtrière, Paris, 9CHU Jean Minjoz, Besançon, 10BioPredictive, Paris, 11Hepatology, CH- Hyeres Hospital, Hyeres, 12CHU Nancy, Nancy, France. *[email protected]

Background: Fibrosis-regression rate in treated chronic hepatitis B (CHB) patients was similar using Fibrotest (Biopredictive) or liver biopsy, while for liver stiffness measurements (LSM) by Fibroscan(Echosens) there was a possible overestimation related to necroinflammatory activity (NIA)(AVT 2010).
Aim: To prospectively evaluate the histological impact of a strong inhibitor of HBV-replication, entecavir motherapy at 0.5mg per day, using non-invasive methods, i.e. FibroMax (including Fibrotest, Actitest, Steatotest for estimating fibrosis, activity and steatosis) and LSM.
Methods: 133-CHB monoinfected, NUC-naive patients were pre-included in 19 centers in France. Data was recorded at baseline(M0), six, and 12-months(M6,M12): viral load, Fibromax [panel of scores (0-1)] and LSM(0-75kPa). Applicability(App) was defined as after exclusion of unreliable LSM and failures. Viral response (VR) was defined as undetectable HBVDNA. Statistics included repeated measures AVOVA (Bonferroni Multiple-Comparison Tests).
Results: 116patients were included [5 lost of follow-up, 9 missing, 3 non-App Fibrotest (acute flare-up ALT>600IU/L)]. Characteristics were: age 44(19-82)yrs; 72%males; 70% anti-HBe(+); 46% Caucasian; 2.6% alcohol>20g/day; median viral load=4.6 logIU/ml; App-LSM 81%(55/68). 31%(N=36) had advanced fibrosis (AF, F2F3F4-METAVIR) and 11%(N=12) cirrhosis as per Fibrotest; 46%(N=53) significant NIA (A1A2A3-METAVIR) as per Actitest; 26%(N=21) had M0 steatosis>1% as per Steatotest. 88 patients achieved M6, 61 M12 with 64% M6-VR and 84% M12-VR. Significant NIA as per ActiTest regressed from M0 0.58(0.03) to M6 0.27(0.03,P< 0.0001) and M12 0.27(0.03,P< 0.0001 vsM0). The same was true for AF as per FibroTest: M0 0.67(0.02) vs M6 0.56(0.02,P=0.0001) and M12 0.54(0.02,P=0.002 vsM0). Among AF-patients without M6 fibrosis-regression, 43% had baseline steatosis>5% as per Steatotest compared to 0% (p=0.04) in AF-patients that regressed fibrosis. As per AF App-LSM no regression was observed vs M0 at M6[8.5(1)vs10.1(1)kPa, P=0.28] but at M12 [6.3(0.4)kPa,P=0.009 vs M0)]. M6 regressions of significant NIA and AF as per Actitest and Fibrotest were observed regardless the VR (vs non-VR) 32% vs 48%(p=0.30) and 38% vs 50% (p=0.74), respectively.
Conclusion: After six and twelve months of entecavir treatment, advanced fibrosis and activity as presumed by Fibrotest-Actitest were significantly reduced, regardless of the viral response. Fibrosis-regression as per liver stiffness measurement was observed only after twelve-month treatment. Patients without fibrosis-regression after 6-months treatment had more baseline steatosis.


Assigned speakers:
Dr. Mona Munteanu, BioPredictive , Paris , France

Assigned in sessions:
26.04.2013, 09:00-18:00, Poster Session, P02-07c, Category 07c: Viral Hepatitis B & D: Clinical (therapy, new compounds, resistance), Poster Area

StephenW

背景：治疗慢性乙型肝炎（CHB）患者纤维化回归率是类似FibroTest的（Biopredictive）或肝活检，而Fibroscan的肝脏硬度测量（LSM）（Echosens）有炎症活动有关的可能的高估（NIA ）2010年（AVT）。
目的：前瞻性评价组织影响HBV复制的强抑制剂，恩替卡韦motherapy的每天0.5毫克，使用非侵入性的方法，即FibroMax（包括FibroTest的Actitest，Steatotest估计纤维化，活动和脂肪变性）和LSM 。
方法：133 CHB monoinfected的，NUC-天真患者被预先包含在19个中心在法国。数据被记录在基线（M0），六，和12个月（M6，M12）：病毒载量，Fibromax [面板的分数（0-1）]和LSM（0-75kPa）。实用性（应用程序）被定义为不可靠的LSM和故障排除后。被定义为HBVDNA检测不到病毒反应（VR）。统计包括重复测量AVOVA（邦费罗尼多对比测试）。
结果：116patients的[5后续损失，9人失踪，3个非应用FibroTest的（急性爆发ALT> 600IU / L）]。特点：44岁（19-82）岁，72％为男性，70％抗-HBe阳性（+），46％白人，2.6％的酒精> 20g/day;病毒载量中位数= 4.6 logIU /毫升APP-LSM 81 ％（55/68）。 31％（N = 36）有先进的纤维化（AF，F2F3F4 METAVIR），11％（N = 12）每FibroTest的肝硬化，46％（N = 53）显着的NIA（A1A2A3 METAVIR）为每Actitest; 26％ （N = 21）M0脂肪肝> 1％为每Steatotest。 88例达到64％M6-VR和84％M12-VR的M6，61 M12。每ActiTest回归显著NIA从M0的0.58（0.03）M6 0.27（0.03，P <0.0001）和M12 0.27（0.03，P <0.0001 vsM0）。同样是真实的AF每FibroTest的：M0 0.67（0.02）与M6 0.56（0.02，P = 0.0001）和M12 0.54（0.02，P = 0.002 vsM0）。其中房颤患者中，43％，没有M6纤维化回归基线脂肪肝> 5％0％（P = 0.04）在AF-回归纤维化的患者相比，每Steatotest。每AF APP-LSM没有回归观察与M0，M6 [8.5（1）vs10.1千帕（1），P = 0.28]，但在M12 [6.3千帕（0.4），P = 0.009与M0）]。无论与非VR（VR）32％与48％（P = 0.30）和38％比50％（P = 0.74），分别观察每Actitest FibroTest的M6回归显著NIA和AF。
结论：恩替卡韦治疗6个月和12个月后，先进如由FibroTest的Actitest的推测纤维化和活动明显减少，不管病毒响应。纤维化回归每肝脏硬度测量，观察后，才12个月的治疗。治疗6个月后，患者无纤维化回归有更多的基线脂肪肝。