Mo1996 Inflammatory Cytokines Are Associated With Hepatic Steatosis and Fibrosis Measured by Computer-Assisted Morphometry (CAM) in Patients With Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH)

Abstract

BACKGROUND: Systemic inflammation has been shown to play an important role in the development and progression of NASH and related fibrosis. AIM: To compare inflammationassociated cytokines with the degree of liver fibrosis and steatosis as measured by computerassisted morphometry (CAM). METHODS: Liver biopsies, clinical data and fasting serum samples had been collected after informed consent. Biopsies were semiquantitatively graded for histopathologic features, and digital images of Sirius red stained sections was used to determine the fraction of collagen and steatosis on a continuous scale by CAM. Serum from the time of liver biopsy was examined with a Bio-Plex Pro Human Cytokine 17-plex assay (Bio-Rad) run on a Bio-Plex 200 (Bio-Rad). RESULTS: 66 NAFLD subjects are included [22 (33.3%) male, 51 (76.6%) Caucasian, 23 (34.8%) diabetes mellitus, 28 (42.4%) with histologic NASH, and 5 (7.6%) with histologic cirrhosis]. The amount of collagen as measured by CAM correlated moderately with the semiquantitative stage of portal fibrosis (r = 0.49, p < 0.0001). The percentage of fat as measured by CAM highly correlated with semiquantitative grade of steatosis (r=0.74, p < 0.0001). Percentage of collagen as measured bymorphometry correlated with IL-1β and IL-7 (r = 0.37, p < 0.01; r = 0.39, p=0.001, respectively). On the other hand, TNF-α was positively associated with both percentage of fat (CAM) and grade of steatosis (r = 0.32, p < 0.01; r = 0.35, p < 0.01, respectively). CONCLUSIONS: These results show that CAM can provide a new dimension to standard histology with the capability of uncovering unsuspected associations with circulating biochemical markers, and may lead to a better understanding of pathogenetic mechanisms in liver disease