Circulating levels and hepatic expression of molecular mediators of atherosclerosis in nonalcoholic fatty liver disease

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+/-34.6ng/ml vs. 356.5+/-24.6ng/ml, p=5.9 x 10(-6)), PAI-1 (22.8+/-1.7ng/ml vs. 19.0+/-2.1ng/ml, p=0.0149) and sCD40L (1347.5+/-513.7pg/ml vs. 804.5+/-396.1pg/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.