Ex Vivo T Cell Cytokine Expression Predicts Survival in Patients with Severe Alcoholic Hepatitis.
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Alcoholic hepatitis (AH) is an acute inflammatory liver condition with high early mortality rate. Steroids have been demonstrated to lead to short-term survival benefits but nonresponders have the worst outcomes. There is a clinical need to identify these high-risk individuals at the time of presentation. T cells have been implicated in AH and steroid responsiveness. We aimed to measure ex vivo T cell cytokine expression as a candidate biomarker of outcomes in patients with AH. Consecutive patients with AH (patients with bilirubin levels >80 µmol/L and the ratio of aspartate aminotransferase to alanine aminotransferase >1.5 who were heavy alcohol consumers with discriminant function [DF] ≥32), were recruited from University Hospitals Plymouth NHS Trust. T cells were obtained and stimulated ex vivo before cytokine expression levels were determined by flow cytometry and protein multiplex analysis. Twenty-three patients were recruited (10 male; median age 51 years; baseline DF 67; 30% 90-day mortality). Compared to T cells from nonsurvivors at day 90, T cells from survivors had higher baseline intracellular IL-10:IL-17A ratios (0.43 vs 1.20, p=0.02). Multiplex protein analysis identified interferon γ (IFNγ) and tumor necrosis factor-α (TNF-α) as independent predictors of 90-day mortality (p=0.04, p=0.01, respectively). The ratio of IFNγ to TNF-α was predictive of 90-day mortality (1.4 vs 0.2, p=0.03). These data demonstrate the potential utility of T cell cytokine release assays performed on pretreatment blood samples as biomarkers of survival in patients with severe AH. Our key findings were that both the ratio of intracellular interleukin (IL)-10 to IL-17A and the ratio of IFNγ to TNF-α in culture supernatants were predictors of 90-day mortality. This offers the promise of developing T cell-based diagnostic tools for risk stratification.
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