Serum interleukin 1 receptor antagonist as an independent marker of 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±9.0years, BMI 44.9±5.9kg/m(2)) were used for histological and gene expression assessment. In a cross-sectional population-based cohort of 6447 men (58±7years, BMI 27.0±3.9kg/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=7×10(-197)) and serum IL-1RA concentration (r(2)=0.074, p=1×10(-110)). IL-1RA concentrations associated significantly with ALT levels even after adjusting for BMI, alcohol consumption and insulin sensitivity (p=2×10(-21)). CONCLUSIONS: IL-1RA serum levels associate with liver inflammation and serum ALT independently of obesity, alcohol consumption and insulin resistance, suggesting a potential use of IL-1RA as a non-invasive inflammatory marker for NASH.[1]References
- Serum interleukin 1 receptor antagonist as an independent marker of non-alcoholic steatohepatitis in humans. Pihlajamäki, J., Kuulasmaa, T., Kaminska, D., Simonen, M., Kärjä, V., Grönlund, S., Käkelä, P., Pääkkönen, M., Kainulainen, S., Punnonen, K., Kuusisto, J., Gylling, H., Laakso, M. J. Hepatol. (2011) [Pubmed]
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