Ex Vivo T Cell Cytokine Expression Predicts Survival in Patients with Severe Alcoholic Hepatitis

• Published in: Gut and liver 2020, 14(2), , pp.265-268
• Main Authors: Dhanda, Ashwin D, Yates, Euan, Schewitz-Bowers, Lauren P, Lait, Philippa J, Lee, Richard W J, Cramp, Matthew E
• Format: Article
• Language: English
• Subjects: alcoholic; biomarker; Biomarkers - blood; Brief Communication; cytokines; Cytokines - blood; Female; hepatitis; Hepatitis, Alcoholic - blood; Hepatitis, Alcoholic - drug therapy; Hepatitis, Alcoholic - mortality; Humans; Interferon-gamma - blood; Interleukin-10 - blood; Interleukin-17 - blood; Male; Middle Aged; Predictive Value of Tests; Risk Assessment; Steroids - therapeutic use; Survival Analysis; t cells; T-Lymphocytes - metabolism; Treatment Outcome; Tumor Necrosis Factor-alpha - blood; 내과학
• ISSN: 1976-2283; 2005-1212
• DOI: 10.5009/gnl19035

Alcoholic hepatitis (AH) is an acute inflammatory liver condition with high early mortality rate. Steroids improve short-term survival but nonresponders have the worst outcomes. There is a clinical need to identify these high-risk individuals at the time of presentation. T cells are implicated in AH and steroid responsiveness. We measured T cell cytokine expression as a candidate biomarker of outcomes in patients with AH. Consecutive patients (bilirubin >80 μmol/L and 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 . 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 baseline intracellular interleukin (IL)-10:IL-17A ratio (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 intracellular IL-10:IL-17A and IFNγ: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.