Ex Vivo T Cell Cytokine Expression Predicts Survival in Patients with Severe Alcoholic Hepatitis
dc.contributor.author | Dhanda, AD | |
dc.contributor.author | Yates, E | |
dc.contributor.author | Schewitz-Bowers, LP | |
dc.contributor.author | Lait, PJ | |
dc.contributor.author | Lee, RWJ | |
dc.contributor.author | Cramp, ME | |
dc.date.accessioned | 2019-07-05T08:48:28Z | |
dc.date.issued | 2019-11-14 | |
dc.identifier.issn | 1976-2283 | |
dc.identifier.issn | 2005-1212 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/14602 | |
dc.description.abstract |
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 ;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 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. | |
dc.format.extent | 265-268 | |
dc.format.medium | ||
dc.language | en | |
dc.language.iso | en | |
dc.publisher | The Editorial Office of Gut and Liver | |
dc.rights | Attribution-ShareAlike 4.0 International | |
dc.rights | Attribution-ShareAlike 4.0 International | |
dc.rights | Attribution-ShareAlike 4.0 International | |
dc.rights | Attribution-ShareAlike 4.0 International | |
dc.rights | Attribution-ShareAlike 4.0 International | |
dc.rights | Attribution-ShareAlike 4.0 International | |
dc.rights | Attribution-ShareAlike 4.0 International | |
dc.rights | Attribution-ShareAlike 4.0 International | |
dc.rights | Attribution-ShareAlike 4.0 International | |
dc.rights | Attribution-ShareAlike 4.0 International | |
dc.rights | Attribution-ShareAlike 4.0 International | |
dc.rights | Attribution-ShareAlike 4.0 International | |
dc.rights | Attribution-ShareAlike 4.0 International | |
dc.rights | Attribution-ShareAlike 4.0 International | |
dc.rights | Attribution-ShareAlike 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | |
dc.subject | Hepatitis | |
dc.subject | alcoholic | |
dc.subject | T cells | |
dc.subject | Cytokines | |
dc.subject | Biomarker | |
dc.title | Ex Vivo T Cell Cytokine Expression Predicts Survival in Patients with Severe Alcoholic Hepatitis | |
dc.type | journal-article | |
dc.type | Article | |
plymouth.author-url | https://www.ncbi.nlm.nih.gov/pubmed/31158952 | |
plymouth.issue | 2 | |
plymouth.volume | 14 | |
plymouth.publisher-url | http://dx.doi.org/10.5009/gnl19035 | |
plymouth.publication-status | Published | |
plymouth.journal | Gut and Liver | |
dc.identifier.doi | 10.5009/gnl19035 | |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/Faculty of Health | |
plymouth.organisational-group | /Plymouth/Faculty of Health/Peninsula Medical School | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine/UoA01 Clinical Medicine | |
plymouth.organisational-group | /Plymouth/Research Groups | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED) | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR | |
plymouth.organisational-group | /Plymouth/Research Groups/Plymouth Institute of Health and Care Research (PIHR) | |
plymouth.organisational-group | /Plymouth/Users by role | |
plymouth.organisational-group | /Plymouth/Users by role/Academics | |
dc.publisher.place | Korea (South) | |
dcterms.dateAccepted | 2019-04-15 | |
dc.rights.embargodate | 2019-12-18 | |
dc.identifier.eissn | 2005-1212 | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.5009/gnl19035 | |
rioxxterms.licenseref.uri | http://creativecommons.org/licenses/by-sa/4.0/ | |
rioxxterms.licenseref.startdate | 2019-11-14 | |
rioxxterms.type | Journal Article/Review |