Serum Intercellular Adhesion Molecule‐1 in Patients With Nonalcoholic Steatohepatitis: Comparison With Alcoholic Hepatitis

Abstract

Nonalcoholic fatty liver disease (NAFLD) includes both nonalcoholic fatty liver (FL) and nonalcoholic steatohepatitis (NASH). It has previously been reported that alcoholic hepatitis, which shows morphological findings similar to that of NASH, leads to the onset of endotoxinemia and to an increase in the production of tumor necrosis factor-alpha (TNF-alpha) and/or interleukin-1 (IL-1) from macrophages. Tumor necrosis factor-alpha and IL-1 induce strong expression of intercellular adhesion molecule-1 (ICAM-1) of the cell membranes of hepatocytes and/or sinusoidal endothelial cells, resulting in increased serum ICAM-1 levels in our previous study. In this study, we clarified the significance of serum ICAM-1 levels in patients with NAFLD, and especially in NASH. Thirty-three obese patients of NAFLD (FL: n=14, NASH: n=19) with no habit of drinking, 20 cases of alcoholic liver diseases (alcoholic hepatitis; ASH: n=10, alcoholic hepatic fibrosis; HF: n=10), and 10 healthy individuals were studied. Serum ICAM-1 concentrations were analyzed by enzyme-linked immunoassay in patients with NAFLD and alcoholic liver diseases. Potential factors were assessed for increase in serum ICAM-1 and a diagnostic tool for NASH including ICAM-1 levels, C-reactive protein (CRP), white blood cell count, aspartate aminotransferase, alanine aminotransferase, gamma-gluatmyl transferase, total cholesterol, triglyceride, type-IV collagen, body mass index, homeostasis model assessment (HOMA-IR), and existence of high blood pressure. The serum ICAM-1 level was significantly higher in the patients with NASH than in the patients with FL, and in the normal subjects. The serum ICAM-1 level was also significantly higher in the patients with ASH. The serum ICAM-1 level in the patients with ASH was remarkably high compared with that of the patients with NASH. No significant difference in serum ICAM-1 levels was found between the patients with NASH and those with HF. The serum ICAM-1 level was significantly higher in patients with high blood pressure than in those without high blood pressure in NAFLD. A multivariate analysis using multiple logistic regression showed that high blood pressure and GGTP were the significant factors contributing to high serum ICAM-1 levels, while highly sensitive CRP and ICAM-1 were the significant factors for the diagnosis of NASH. The serum ICAM-1 concentration is increased in patients with NASH. The serum level of ICAM-1 in patients with NAFLD may be a useful marker for the diagnosis of NASH.