|
Author:
|
J.M. Estep1, Z. Goodman1,2, A. Zirzow3, A. Afendy2, H. Elariny2, A. Baranova1,3, Z.M. Younossi1,4,5*
|
|
Affiliation:
|
1Betty and Guy Beatty Center for Integrated Research, Inova Health System, 2Center for Liver Disease, Inova Fairfax Hospital, Falls Church, 3Center for the Study of Genomics in Liver Diseases, George Mason University, Fairfax, 4Center for Liver Diseases, 5Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA. *zobair.younossi@inova.org
|
Background and aim: FASLG and IL20 may contribute to the pathogenesis of non-alcoholic steatohepatitis (NASH) by promoting hepatocyte apoptosis. Omental adipose tissue (OAT) is a biologically active organ producing adipo-cytokines with potentially important roles in the pathogenesis of NASH. Previously, we have demonstrated an increased expression of IL20 and FASLG in the OAT of NASH patients. The aim of this study was to establish the presence/absence of receptors for IL20 and FASLG in the liver tissue of NAFLD patients.
Methods: OAT samples were collected from biopsy proven NAFLD patients. Based on liver biopsy readings by a single hepatopatholgist, patients were divided into NASH (n=12) and non-NASH NAFLD (n=12) cohorts controlled for clinico-demographic characteristics. IL20 and FASLG expression was assessed by qPCR. Liver tissue obtained at the same time as OAT collection was stained by standard IHC methods for FAS or IL20R-alpha. Slides were assessed by hepatopathologist by assigning a rating of 0-4 to indicate the percentage of hepatocytes, bile duct cells, or kupfer cells stained in their nucleus, cytoplasm, or membranes (0=stain undetected,1=< 5%,2=5-33%,3=34-66%,4>66%) Comparisons were made by Mann-Whitney test and Spearman rank correlations.
Results: Expression of IL20 (FD=2.8,P=0.05) and FASLG (FD=2.5, P=0.03) was higher in OAT of NASH patients. In stained liver biopsies, IL20 levels (FD=5.7, P< 0.01) and FASLG (FD=57, P< 0.01) were both increased in NASH patients. IL20R-alpha stained the hepatocyte nucleus, cytoplasm, and nuclei of bile duct cells (ave.rating>3); occasionally staining the cytoplasm of Kupfer and endothelial cells (ave.rating< 1). Staining showed FAS in the nucleus and cytoplasm of both hepatocytes (ave.rating>1 and >2, respectively) and bile duct cells (ave.rating>1,>2, respectively). Nuclear FAS expression strongly correlated with ballooning degeneration (r=0.71,p= 0.02), presence of histologic NASH (r=0.59,P=0.07), serum triglycerides (r=0.7,p= 0.02), and FASLG expression in OAT (r=0.51,P=0.09 ).
Conclusions: IL20 and FASLG are differentially expressed in OAT of patients with NASH. Receptors for these cytokines are expressed in the liver tissue of these patients. Correlation of FAS expression in the liver with that of FASLG from OAT, as well as clinico-laboratory data, implied a direct role for OAT in promoting hepatic apoptosis involved in NASH.
|
