studies

910A AASLD ABSTRACTS HEPATOLOGY, October, 2015
Disclosures:
The following authors have nothing to disclose: Theerut Luangmonkong, Suriguga
Suriguga, Emilia Bigaeva, Dorenda Oosterhuis, Koert P. de Jong, Detlef Schuppan,
Henricus A. Mutsaers, Peter Olinga
1435
Serum lysyl oxidase-like-2 (sLOXL2) levels correlate with
fibrosis stage in patients with nonalcoholic steatohepatitis
(NASH)
Stephen A. Harrison 1 , Zachary D. Goodman 2 , Vlad Ratziu 3 , Rohit
Loomba 4 , Anna Mae Diehl 5 , Eric Lawitz 6 , Holger Hinrichsen 7 ,
Kiran Bambha 8 , Manal F. Abdelmalek 5 , Robert P. Myers 9 , Raul
E. Aguilar Schall 9 , Mani Subramanian 9 , John G. McHutchison 9 ,
Nezam H. Afdhal 10 , Andrew J. Muir 5 ; 1 San Antonio Military
Medical Center, Fort Sam Houston, TX; 2 Inova Fairfax Hospital,
Falls Church, VA; 3 Hôpital Pitié-Salpêtrière, Paris, France; 4 University
of California at San Diego, San Diego, CA; 5 Duke Clinical
Research Institute, Durham, NC; 6 Texas Liver Institute, University
of Texas Health Science Center, San Antonio, TX; 7 Gastroenterologisch-Hepatologisches
Zentrum, Kiel, Germany; 8 University of
Colorado Denver, Aurora, CO; 9 Gilead Sciences, Inc., Foster City,
CA; 10 Beth Israel Deaconess Medical Center and Harvard Medical
School, Boston, MA
Background: LOXL2 plays a central role in liver fibrosis by
catalyzing collagen cross-linkage. Our aim was to examine
the association between sLOXL2 and disease severity in
patients with advanced fibrosis due to NASH. 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). sLOXL2 was measured using an immunoassay
(VIDAS® LOXL2; bioMérieux, Marcy L’Etoile, France)
in NASH patients and 50 healthy controls. Liver biopsies were
graded centrally according to the NAFLD Activity Score (NAS)
and fibrosis was staged according to the Ishak classification.
The associations between sLOXL2 and fibrosis stage, NAS,
demographics, body mass index (BMI), diabetes, liver biochemistry,
MELD, and fibrosis markers (FibroTest, ELF, APRI,
FIB-4, NAFLD Fibrosis Score [NFS]) were determined. Results:
474 of 477 randomized patients (99.4%) with available
sLOXL2 and stage 3-6 fibrosis were included. The median age
was 56 years (IQR 50-60), 63% were female, 68% had diabetes,
the median BMI was 33.6 kg/m 2 (IQR 29.8-38.2), and the
median serum ALT was 39 U/L (IQR 28-62). Median sLOXL2
was higher in patients with NASH than controls (107 pg/mL
[IQR 82-147] vs. 81 pg/mL [IQR 71-108]; P