Serum interleukin 1 receptor antagonist as an independent marker off non-alcoholic steatohepatitis in humans

Background & Aims: Mechanisms leading to non-alcoholic steatohepatitis (NASH) have remained unclear, and non-invasive diagnosis of NASH is challenging. In this study, we investigated the benefits of measuring serum interleukin 1 receptor antagonist (IL-1RA) levels. Methods: Liver biopsies from 119 morbidly obese individuals (47.5 +/- 9.0 years, BMI 44.9 +/- 5.9 kg/m(2)) were used for histological and gene expression assessment. In a cross-sectional population-based cohort of 6447 men (58 +/- 7 years, BMI 27.0 +/- 3.9 kg/m(2)) the association of serum IL1-RA with serum alanine aminotransferase (ALT) levels was investigated. Results: Serum levels of IL-1RA, and liver mRNA expression of IL1RN are associated with NASH and the degree of lobular inflammation in liver (p<0.05). The decrease in serum IL-1RA level and expression of IL1RN after obesity surgery correlated with the improvement of lobular inflammation (p<0.05). We developed a novel NAFLD Liver Inflammation Score, including serum Il-1RA concentration, which performed better to diagnose NASH than did previously published scores. Results from the population study confirmed the potential of measuring serum IL-1RA level. The strongest determinants of the ALT concentration at the population level were Matsuda insulin sensitivity index (r(2) = 0.130, p = 7 x 10(-197)) and serum IL-1RA concentration (r(2) = 0.074, p = 1 x 10(-110)). IL-1RA concentrations associated significantly with ALT levels even after adjusting for BMI, alcohol consumption and insulin sensitivity (p = 2 x 10(-21)). Conclusions: IL-1RA serum levels associate with liver inflammation and serum ALT independently of obesity, alcohol consump tion and insulin resistance, suggesting a potential use of IL-1RA as a non-invasive inflammatory marker for NASH. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.