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.