Serum interleukin 1 receptor antagonist as an independent marker of non-alcoholic steatohepatitis in humans.
OBJECTIVE
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 × 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.
Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland. jussi.pihlajamaki@uef.fi
Jussi
J
Pihlajamäki
Tiina
T
Kuulasmaa
Dorota
D
Kaminska
Marko
M
Simonen
Vesa
V
Kärjä
Sari
S
Grönlund
Pirjo
P
Käkelä
Matti
M
Pääkkönen
Sakari
S
Kainulainen
Kari
K
Punnonen
Johanna
J
Kuusisto
Helena
H
Gylling
Markku
M
Laakso
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D005234:Fatty Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood* / Q000235:genetics; D008049:Lipase / Q000235:genetics; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D009767:Obesity, Morbid / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
D000410:Alanine Transaminase; D015415:Biomarkers; D053590:Interleukin 1 Receptor Antagonist Protein; D008049:Lipase; D008565:Membrane Proteins; C507763:IL1RN protein, human; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent