studies

906A AASLD ABSTRACTS HEPATOLOGY, October, 2015
in SPF mouse liver slices. These results indicate that PAMPs are
profibrotic in the absence of microbiota, whereas in SPF mice
the microbiota might confer hepatoprotection, which attenuates
the onset of fibrosis by PAMPs in SPF PCLS. Moreover, LPS
may rely on the TGF-β signaling pathway to elicit a fibrotic
response, while flagellin might depend on other pathways.
Disclosures:
The following authors have nothing to disclose: Suriguga Suriguga, Floris Fransen,
Dorenda Oosterhuis, Geny M. Groothuis, Paul D. Vos, Henricus A. Mutsaers,
Peter Olinga
1428
Correlations between hepatic morphometric collagen
content, histologic fibrosis staging, and serum markers
in patients with advanced fibrosis due to nonalcoholic
steatohepatitis (NASH)
Zachary D. Goodman 1 , Lakshmi Alaparthi 1 , Fanny Monge 1 , Keyur
Patel 2 , Rohit Loomba 3 , Stephen H. Caldwell 4 , Eric Lawitz 5 , Stephen
A. Harrison 6 , Mitchell L. Shiffman 7 , Manal F. Abdelmalek 2 ,
Robert P. Myers 8 , Raul E. Aguilar Schall 8 , Mani Subramanian 8 ,
John G. McHutchison 8 , Vlad Ratziu 9 , Arun J. Sanyal 10 , Nezam
H. Afdhal 11 ; 1 Inova Fairfax Hospital, Falls Church, VA; 2 Duke
Clinical Research Institute, Durham, NC; 3 University of California
at San Diego, San Diego, CA; 4 University of Virginia, Charlottesville,
VA; 5 Texas Liver Institute, University of Texas Health Science
Center, San Antonio, TX; 6 San Antonio Military Medical Center,
Fort Sam Houston, TX; 7 Liver Institute of Virginia, Richmond, VA;
8 Gilead Sciences, Inc., Foster City, CA; 9 Hopital Pitie-Salpretriere,
Paris, France; 10 Virginia Commonwealth University, Richmond,
VA; 11 Beth Israel Deaconess Medical Center and Harvard Medical
School, Boston, MA
Background: Our aim was to determine the relationships
between hepatic collagen assessed by morphometry with serum
fibrosis markers, Ishak fibrosis staging, and other histologic
features of NASH in patients with advanced fibrosis. Methods:
The study included adults with NASH and bridging fibrosis
(Ishak stage 3 or 4) or cirrhosis (stage 5 or 6) enrolled in two
phase 2b trials 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 in sirius red-stained biopsies was quantified via computer-assisted
morphometry. Serum LOXL2 (sLOXL2) was measured
using an immunoassay (VIDAS® LOXL2; bioMérieux,
Marcy L’Etoile, France). The associations between hepatic collagen
and Ishak fibrosis stage, noninvasive fibrosis markers
(sLOXL2, FibroTest, ELF, APRI, FIB-4, and NAFLD Fibrosis Score
[NFS]), and the NAS and its components were determined.
Results: 429 of 477 randomized patients (89.9%) with biopsies
acceptable for computerized morphometry were included.
The median age was 56 years (IQR 50-60), 62% were female,
52% had cirrhosis, and the median hepatic collagen content
was 8.4% (IQR 5.2-14.7%). Hepatic collagen was moderately
correlated with fibrosis stage (Spearman ρ=0.59; P