AASLD 2013:2年恩替卡对肝纤维化Fibroscan,FibroTest-ACtiTest活动影响

StephenW

TITLE: 2-years impact of entecavir (ETV) on liver fibrosis and activity as assessed by the non-invasive methods of FibroTest-ActiTest (FT-AT) and liver stiffnesse measurements (LSM) by Fibroscan in patients with chronic hepatitis B (CHB)
AUTHORS (FIRST NAME, LAST NAME): 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 Munteanu 9, Thierry Poynard8
Institutional Author(s): ENTEFIB Study Group
INSTITUTIONS (ALL): 1. Hepato-Gastroenterology, Hospices Civiles de Lyon, Lyon, France.
2. Hepato-Gastroenterology, CHR Orleans La Source, Orleans, France.
3. Hepato-Gastroenterology, CHU Grenoble, Grenoble, France.
4. Hepato-Gastroenterology, Institut Arnaud Tzanck, Saint Laurent du Var, France.
5. Hepato-Gastroenterology, CH Jean Verdier, Bondy, France.
6. Hepato-Gastroenterology, CH Haut Leveque, Bordeaux, France.
7. Hepato-Gastroenterology, CHU Lille, Lille, France.
8. Hepato-Gastroenterology, APHP UPMC Liver Center, Paris, France.
9. Hepatology Research Unit, BioPredictive, Paris, France.
ABSTRACT BODY: 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. F 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.

StephenW

治疗慢性乙型肝炎（ CHB ）患者的回归Background.Fibrosis率是相似FibroTest的（ Biopredictive ）或肝活检，而Fibroscan的肝脏硬度测量（LSM） （ Echosens ）与坏死性炎症有可能是高估活动（ NIA ） 2010年（ AVT ） 。 Aim.To组织影响HBV复制的强抑制剂，恩替卡韦motherapy的前瞻性评估，使用非侵入性的方法，即在每天0.5mg的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） 。的结果。 116patients [5失去随访， 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 （ + ） ，46％
白人2.6 ％的酒精> 20g/day的病毒载量中位数= 4.6 logIU /毫升; App - LSM的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，不管病毒反应。 F纤维化回归肝脏硬度测量每12个月的治疗后，才观察到。治疗6个月后，患者无纤维化回归有更多的基线脂肪肝。