Persistent Hyperactivation of Endothelial Cells in Patients with Alcoholic Hepatitis.

BACKGROUND: Alcoholic hepatitis (AH) is a severe inflammatory liver disease that develops in some heavy drinkers. AH patients have intense hepatic infiltration of leukocytes. Upregulation of cell adhesion molecules (CAMs) upon endothelial cell (EC) activation plays an important role in leukocyte trans-endothelial migration. CAMs can shed from EC cell surface and accumulate in the blood, serving as soluble markers for EC activation. In this study, we examined the impact of heavy drinking on expression of soluble forms of EC activation markers (CD146, ICAM-1, VCAM-1, and VEGF-A) and the effect of alcohol abstinence on the reversal of these abnormalities in patients with and without AH. METHODS: ELISA and multiplex immunoassays were used to measure soluble EC markers in plasma samples from 79 AH patients, 66 heavy drinkers without overt liver disease (HDC), and 44 healthy controls (HC) at baseline, 31 AH patients and 30 HDC at 6-month follow-up, and 18 AH patients and 25 HDC at 12-month follow-up. RESULTS: At baseline, the 4 soluble markers were significantly upregulated in AH patients compared to HDC and HC; whereas only sVCAM-1 was elevated in HDC relative to HC. At follow-ups, plasma levels of CD146, VCAM-1, and VEGF-A remained higher in AH patients, even for those who stopped drinking. These dysregulated markers correlated with AH disease severity, clinical parameters, and several soluble factors. CONCLUSIONS: The levels of soluble CD146, ICAM-1, VCAM-1, and VEGF-A were highly elevated in AH patients, and alcohol abstinence did not completely reverse these abnormalities.