Introduction Acute Alcoholic Hepatitis (AAH) is the most florid form of alcohol-related liver disease (ALD) with a mortality rate in the first 28 days of over 30%. These patients are particularly prone to developing infections with a high risk of developing multiple organ failure including hepatic encephalopathy, renal failure and circulatory collapse. The vascular endothelium becomes activated in severe sepsis allowing the influx of inflammatory cells from the circulation. Angiopoeitin (ANG) 1 and 2 are key to endothelial cell (EC) activation. On activation by stimuli such as pro-inflammatory cytokines, ECs release Wiebel-Palade bodies liberating ANG 2. ANG 2 competitively inhibits ANG 1, renders the endothelium responsive to further cytokine stimulation and disrupts cell-cell adhesion increasing vascular permeability. In sepsis plasma levels of ANG 1 and 2 have been implicated as potential prognostic biomarkers. Considering that patients with severe AAH and ALD have evidence of a systemic pro-inflammatory milieu this study measured plasma levels of ANG 1 and ANG 2 as surrogate biomarkers of EC dysfunction.
Methods Thirty patients with severe AAH (Maddrey’s discriminant factor >32) and a history of alcohol excess (≥80 g/day for males; ≥60 g/day for females) were studied at presentation prior to any therapy being prescribed and compared to healthy controls (HC) (n = 7). Twenty one patients with ALD (Child Pugh C) were also studied. Exclusion criteria included alcohol abstinence >6 weeks, other causes of liver disease, malignancy, concomitant use of immunosuppression ≤6 months and AST > 500 IU/L. Plasma levels of ANG 1 and ANG 2 were measured by enzyme-linked immunosorbent assay (ELISA).
Results Plasma levels of ANG 2 were found to be significantly higher in the AAH group compared to HC (p < 0.0001) and in the AAH group compared to ALD (p < 0.05). The ANG 2:1 ratio was also significantly higher in the AAH group compared to HC (p < 0.001), and in the AAH group compared to ALD (p < 0.05). ANG 2 and ANG 2:1 ratio trended towards being higher in culture positive AAH patients (p = 0.065). In this study there was no statistically significant difference in any marker level between non-surviving (at 1 month) and surviving AAH patients.
Conclusion Plasma levels of ANG 2, a soluble biomarker of endothelial activation, and the ANG 2:1 ratio are increased in AAH and could predict the subsequent development of organ failure.
Disclosure of Interest None Declared
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