Persistent Hyperactivation of Endothelial Cells in Patients with Alcoholic Hepatitis

Ying Xia, Jing Yang, Arun J. Sanyal, Vijay H. Shah, Naga P. Chalasani, Qigui Yu, Xiaoqun Zheng, Wei Li

Research output: Contribution to journalArticle

Abstract

Background: Alcoholic hepatitis (AH) is a severe inflammatory liver disease that develops in some heavy drinkers. AH patients have intense hepatic infiltration of leukocytes. Up-regulation of cell adhesion molecules (CAMs) upon endothelial cell (EC) activation plays an important role in leukocyte transendothelial migration. CAMs can shed from EC 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 heavy drinkers with and without AH. Methods: ELISA and multiplex immunoassays were used to measure soluble EC activation 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 up-regulated in AH patients compared with 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 inflammatory 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.

Original languageEnglish (US)
Pages (from-to)1075-1087
Number of pages13
JournalAlcoholism: Clinical and Experimental Research
Volume44
Issue number5
DOIs
StatePublished - May 1 2020

Keywords

  • Adhesion Markers
  • Alcoholic Hepatitis
  • Endothelial Activation
  • Longitudinal Study
  • Soluble Forms

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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