Correlation between the Hepatic Venous Pressure Gradient and Alpha-Smooth Muscle Actin (SMA) Expression in Patients with Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis

POSTER PRESENTATIONS 29%; p = 0.004). Multivariate analysis identified as independent factors for 30-day mortality at admission the variables sepsis ( p = 0.003; OR = 6.842), MELD > 26 ( p = 0.036; OR = 3.690) and SBP-MDR ( p = 0.010; OR = 4.730). Conclusions: Our data showed a high and alarming prevalence of SBP caused by MDR bacteria (13%), especially when analyzed community acquired SBP (6%). MDR-SBP was associated with a worst short-term prognosis. THU-016 CORRELATION BETWEEN THE HEPATIC VENOUS PRESSURE GRADIENT AND ΑLPHA-SMOOTH MUSCLE ACTIN (SMA) EXPRESSION IN PATIENTS WITH COMPENSATED CIRRHOSIS DUE TO NONALCOHOLIC STEATOHEPATITIS A. Sanyal1, Z. Goodman2, S. Harrison3, D.C. Rockey4, A.M. Diehl5, S. Caldwell6, M.L. Shiffman7, P. Thuluvath8, R.P. Myers9, G. Mani Subramanian9, J.G. McHutchison9, M.F. Abdelmalek5, V. Ratziu10, N. Afdhal11, J. Bosch12. 1Virginia Commonwealth University, Richmond; 2 Inova Fairfax Hospital, Falls Church; 3San Antonio Military Medical Center, Fort Sam Houston; 4Medical University of South Carolina, Charleston; 5Duke Clinical Research Institute, Durham; 6University of Virginia, Charlottesville; 7Liver Institute of Virginia, Richmond; 8Mercy Medical Center, Baltimore; 9Gilead Sciences, Inc., Foster City, United States; 10Hôpital Pitié-Salpêtrier̀ e, Paris, France; 11Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States; 12 University of Barcelona, Barcelona, Spain E-mail: [email protected] Background and Aims: Our objective was to examine the association between hepatic α-SMA expression, a marker of stellate cell and myofibroblast activation, and the hepatic venous pressure gradient (HVPG) in patients with compensated cirrhosis due to nonalcoholic steatohepatitis (NASH). Methods: The study included adults with compensated cirrhosis (Ishak 5 or 6) due to NASH enrolled in a phase 2b trial of simtuzumab, a monoclonal antibody against lysyl oxidase-like-2 (LOXL2). Liver biopsies were evaluated centrally according to the Ishak staging system and NAFLD Activity Score (NAS). Hepatic collagen was quantified via computer-assisted morphometry of picrosirius redstained liver sections. αSMA expression was quantified by immunolabeling of liver sections, also via morphometry. HVPG was measured according to a standardized protocol and reviewed centrally. Serum LOXL2 (sLOXL2) levels were measured by immunoassay (VIDAS® LOXL2; BioMérieux, Marcy L’Etoile, France). Logistic regression models evaluated independent predictors of clinically significant portal hypertension (CSPH, defined as HVPG ≥10 mmHg) including α-SMA expression, fibrosis stage, and sLOXL2. Results: 229 of 258 randomized patients (89%) with HVPG, fibrosis staging, and α-SMA quantitation were included. The median age was 56 years, 62% were female, and 41% (91/222) had NAS ≥5.67% of patients had stage 6 fibrosis, 67% had CSPH (median HVPG, 12 mmHg [IQR 8.5–16.5]), 20% had ≥ grade 2 varices, and 21% were prescribed non-selective beta blockers (NSBBs). By morphometry, the median hepatic collagen content was 12.5% (IQR 8.2–19.5%) and α-SMA was 18.2% (IQR 11.9–25.9%). α-SMA was moderately correlated with HVPG (ρ = 0.33; Figure), Ishak stage (ρ = 0.45), hepatic collagen (ρ = 0.45), and sLOXL2 (ρ = 0.22; all p < 0.005). Patients with CSPH had higher α-SMA expression than patients with HVPG <10 mmHg (20.6% vs. 15.6%; p < 0.0001). In a multivariate model including demographics, Ishak stage, sLOXL2 and NSBB treatment, CSPH was associated with higher fibrosis stage (stage 6 vs. 5: odds ratio [OR]: 2.45; 95% CI 1.19–5.01), BMI (OR 1.07; 1.01–1.13), female sex (OR 2.58; 1.29– 5.16), sLOXL2 (OR 1.02; 1.01-1.02), and α-SMA expression (OR 1.04; 1.00–1.09; p = 0.041).

Conclusions: In patients with compensated cirrhosis due to NASH, fibrosis stage, sLOXL2, and immunohistochemical α-SMA expression were independent predictors of CSPH. These findings suggest that stellate cell and myofibroblast activation may contribute to CSPH and raise the possibility that effective anti-fibrotic agents may improve CSPH. THU-017 PROGNOSTICATING AFTER VARICEAL BLEED IN CRYPTOGENIC CIRRHOSIS: NON CIRRHOTIC PORTAL HYPERTENSION CAN BE A CONFOUNDER A. Goel1, B. Ramakrishna2, U. Zachariah1, K.G. Sajith1, G. Chandy1, G. Kurian1, C.E. Eapen1. 1Hepatology; 2Pathology, Christian Medical College, Vellore, India E-mail: [email protected] Background and Aims: Stage 4 cirrhosis (variceal bleed ± ascites) predicts 57% 1-year mortality (D’Amico et al., J Hepatol 2006). Idiopathic non-cirrhotic intrahepatic portal hypertension (NCIPH), a portal vein microangiopathy, maybe mis-labelled as cryptogenic “cirrhosis”, if liver biopsy is not done. This study aims to assess survival after variceal bleed in NCIPH patients. Methods: Prospectively collected database of NCIPH patients in our institution was retrospectively analysed for baseline characteristics and time to first decompensation (ascites, encephalopathy, variceal bleed, vascular complications), to portal vein thrombosis and to terminal event (death, liver transplant or terminal condition). Results: From 1996 to 2015, 174 patients (M:112; Age: 32 ± 11.7 years; Child’s score:5, 5–6; median, IQR) with liver biopsy proven NCIPH were recruited for the study. Patients presented 12 (4–48; median, IQR) months after initial symptoms of enlarged spleen (47%), variceal bleed (38%) and ascites (17%). HVPG (n = 121) was 7 (4–10.5, median, IQR) (HVPG ≤5 mm Hg in 42 (35%) patients). 107 patients were followed up for ≥3 months (mean follow up 33 ± 39 months). 28 patients developed portal vein thrombosis at 140 (95% C.I: 115– 165) months. 1 and 5 year portal vein thrombosis free survival was 97% (2%) and 84% (4%). 26 patients developed decompensation (ascites: 18, bleed: 4, encephalopathy: 2, HPS: 1, porto-pulmonary hypertension:1); median time to decompensation : 164 (95%C.I: 90–239) months. 1 and 5 year decompensation free survival was 97% (2%) and 83% (5%), estimate (S.E). Time to decompensation was similar in patients presenting with variceal bleed (86 months, 95%C. I:83–89 months) or without variceal bleed (172 (128-216) months; p-value: 0.3). 1 patient died, 2 underwent liver transplantation and 2 developed terminal condition secondary to hepatocellular carcinoma. Figure shows terminal event free survival in patients with and without variceal bleed ( p-value: 0.4). 1 year and 5 year event free survival in patients with variceal bleed was 95% (3%) and 91% (5%). 1 year and 5 year terminal event free survival in patients with either ascites or variceal bleed at presentation was 97% (2%) and 92% (5%) respectively. NCIPH recurred in 1 patient, 11 years after liver transplantation.

Journal of Hepatology 2016 vol. 64 | S213–S424

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