Abstract
Objectives
We evaluated circulating levels of biomarkers of atherosclerosis (soluble intercellular
adhesion molecule: sICAM-1, plasminogen activator inhibitor: PAI-1 and soluble CD40
ligand: sCD40L) in patients with NAFLD proven through biopsy and control subjects,
and correlated them with the histological disease severity. We further explored liver
protein expression of ICAM-1, CD40 and PAI-1 in patients with different histological
forms of NAFLD and control liver biopsies.
Patients and methods
We included 215 individuals: 113 patients with NAFLD (simple steatosis n = 45 and NASH n = 68) and 102 control subjects. Circulating levels of the biomarkers were measured by
ELISA. Liver expression of ICAM-1, CD40 and PAI-1 was assessed by immunohistochemistry
using monoclonal antihuman antibodies.
Results
Patients with NAFLD, in comparison with control subjects, showed significantly higher
circulating levels of sICAM-1 (605.3 ± 34.6 ng/ml vs. 356.5 ± 24.6 ng/ml, p = 5.9 × 10−6), PAI-1 (22.8 ± 1.7 ng/ml vs. 19.0 ± 2.1 ng/ml, p = 0.0149) and sCD40L (1347.5 ± 513.7 pg/ml vs. 804.5 ± 396.1 pg/ml, p = 0.0229), results expressed as mean ± SE. sICAM-1 was a strong predictor of histological severity of NAFLD, after adjusting
for potential confounders. In addition, patients with NAFLD showed significantly higher
liver staining scores for ICAM-1 and PAI-1 than control liver biopsies. ICAM-1 immunoreactivity
in lobular inflammatory infiltrate showed high scores in NASH patients; a significant
correlation was found between both the degree of liver steatosis and the severity
of necroinflammatory activity and liver ICAM-1 expression.
Conclusions
Our study shows that NAFLD is associated with elevated circulating levels and abnormal
liver expression of molecular mediators of atherosclerosis. Additionally, ICAM-1 may
be involved in liver damage and inflammation.
Abbreviations:
NAFLD (nonalcoholic fatty liver disease), NASH (nonalcoholic steatohepatitis), PAI-1 (plasminogen activator inhibitor-1), sICAM-1 (soluble intercellular adhesion molecule-1), sCD40L (soluble CD40 ligand), ELISA (enzyme-linked immuno-sorbent assay)Keywords
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Article Info
Publication History
Published online: November 06, 2009
Accepted:
October 5,
2009
Received in revised form:
September 1,
2009
Received:
July 31,
2009
Identification
Copyright
© 2009 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
