studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 577A
737
Clinical and histologic correlates of the hepatic venous
pressure gradient (HVPG) in patients with compensated
cirrhosis due to nonalcoholic steatohepatitis (NASH)
Arun J. Sanyal 1 , Zachary D. Goodman 2 , Manal F. Abdelmalek 3 ,
Stephen A. Harrison 4 , Don C. Rockey 5 , Anna Mae Diehl 3 , Stephen
H. Caldwell 6 , Mitchell L. Shiffman 7 , Robert P. Myers 8 , Raul E.
Aguilar Schall 8 , Mani Subramanian 8 , John G. McHutchison 8 , Vlad
Ratziu 9 , Nezam H. Afdhal 10 , Jaime Bosch 11 ; 1 Virginia Commonwealth
University, Richmond, VA; 2 Inova Fairfax Hospital, Falls
Church, VA; 3 Duke Clinical Research Institute, Durham, NC; 4 Fort
Sam Houston, San Antonio Military Medical Center, San Antonio,
TX; 5 Medical University of South Carolina, Charleston, SC; 6 University
of Virginia, Charlottesville, VA; 7 Liver Institute of Virginia,
Richmond, VA; 8 Gilead Sciences, Inc., Foster City, CA; 9 Hôpital
Pitié-Salpêtrière, Paris, France; 10 Beth Israel Deaconess Medical
Center and Harvard Medical School, Boston, MA; 11 University of
Barcelona, Barcelona, Spain
Background: Clinical complications in patients with cirrhosis
are predominantly linked to the severity of portal hypertension.
Our objective was to examine clinical and histologic correlates
of the HVPG in patients with compensated cirrhosis due to
NASH. Methods: The study included adults with compensated
cirrhosis (Ishak 5 or 6) due to NASH who were enrolled in a
phase 2b trial of simtuzumab, a monoclonal antibody against
lysyl oxidase-like-2 (LOXL2). Liver biopsies were graded centrally
according to the NAFLD Activity Score (NAS) and hepatic
collagen was quantified via computer-assisted morphometry.
HVPG was measured according to a standardized protocol
and reviewed centrally. Serum LOXL2 (sLOXL2) was measured
using an immunoassay (VIDAS® LOXL2; bioMérieux, Marcy
L’Etoile, France). The associations between HVPG and age,
sex, body mass index (BMI), diabetes, use of non-selective beta
blockers (NSBBs), esophageal varices, laboratory variables,
fibrosis stage, hepatic collagen, and NAS and its elements
were determined. Stepwise-forward, logistic regression models
evaluated independent predictors of clinically significant
portal hypertension (CSPH, defined as an HVPG ≥10 mmHg).
Results: 230 of 258 randomized patients (89.1%) with HVPG
and complete histologic data were included. The median age
was 56 years (IQR 51-61), 63% were female, 67% had stage
6 fibrosis, 40% had a NAS ≥5, and the median hepatic collagen
content was 12.5% (n=218 with complete data; IQR
8.1-19.4%). The median HVPG was 12 mmHg (IQR 9-16.5)
and 69% had CSPH. The HVPG was weakly correlated with
hepatic collagen content (Spearman ρ=0.19; P=0.004) and
moderately correlated with sLOXL2 (ρ=0.50; P