Ex Vivo T Cell Cytokine Expression Predicts Survival in Patients with Severe Alcoholic Hepatitis
- Author:
Ashwin D. DHANDA
1
;
Euan YATES
;
Lauren P. SCHEWITZ-BOWERS
;
Philippa J. LAIT
;
Richard W. J. LEE
;
Matthew E. CRAMP
Author Information
- Publication Type:Brief communication
- From:Gut and Liver 2020;14(2):265-268
- CountryRepublic of Korea
- Language:English
- Abstract: Alcoholic hepatitis (AH) is an acute inflammatory liver condition with high early mortality rate. Steroids improve shortterm 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 ex vivo 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 ex vivo. 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 nonsur-vivors 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 pre-dictors of 90-day mortality. This offers the promise of devel-oping T cell-based diagnostic tools for risk stratification.
