In severe alcohol-related hepatitis, acute kidney injury is prevalent, associated with mortality independent of liver disease severity, and can be predicted using IL-8 and micro-RNAs
In severe alcohol-related hepatitis, acute kidney injury is prevalent, associated with mortality independent of liver disease severity, and can be predicted using IL-8 and micro-RNAs
Background: the prevalence, prediction and impact of acute kidney injury (AKI) in alcohol-related hepatitis (AH) is uncertain.
Aims: we aimed to determine AKI incidence; association with mortality; evaluate serum biomarkers and the modifying effects of prednisolone and pentoxifylline in the largest AH cohort to date.
Methods: participants in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial with day zero (D0) creatinine available were included. AKI was defined by modified International Club of Ascites criteria; incident AKI as day 7 (D7) AKI without D0-AKI. Survival was compared by Kaplan-Meier; mortality associations by Cox regression; associations with AKI by binary logistic regression; biomarkers by AUROC analyses.
Results: D0-AKI was present in 198/1051 (19%) participants; incident AKI developed in a further 119/571 (21%) with available data. Participants with D0-AKI had higher 90-day mortality than those without (32% vs. 25%, p = 0.008), as did participants with incident AKI compared to those without D0-AKI or incident AKI (47% vs. 25%, p < 0.001). Incident AKI was associated with D90 mortality adjusted for age and discriminant function (AHR 2.15, 1.56-2.97, p < 0.001); D0-AKI was not. Prednisolone therapy reduced incident AKI (AOR 0.55, 0.36-0.85, p = 0.007) but not mortality. D0 bilirubin and IL-8 combined, miR-6826-5p, and miR-6811-3p predicted incident AKI (AUROCs 0.726, 0.821, 0.770, p < 0.01).
Conclusions: incident AKI is associated with 90-day mortality independent of liver function. Prednisolone therapy was associated with reduced incident AKI. IL-8 and several miRNAs are potential biomarkers to predict AKI. Novel therapies to prevent incident AKI should be evaluated in AH to reduce mortality.
1217-1229
Tyson, Luke D.
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Atkinson, Stephen
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Hunter, Robert W.
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Allison, Michael
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Austin, Andrew
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Dear, James W.
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Forrest, Ewan
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Liu, Tong
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Lord, Emma
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Masson, Steven
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Nunes, Joao
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Richardson, Paul
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Ryder, Stephen D.
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Wright, Mark
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Thursz, Mark
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Vergis, Nikhil
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December 2023
Tyson, Luke D.
a94b0640-e108-407f-b599-5db143e5ea2f
Atkinson, Stephen
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Hunter, Robert W.
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Allison, Michael
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Austin, Andrew
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Dear, James W.
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Forrest, Ewan
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Liu, Tong
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Lord, Emma
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Masson, Steven
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Nunes, Joao
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Richardson, Paul
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Ryder, Stephen D.
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Wright, Mark
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Thursz, Mark
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Vergis, Nikhil
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Tyson, Luke D., Atkinson, Stephen, Hunter, Robert W., Allison, Michael, Austin, Andrew, Dear, James W., Forrest, Ewan, Liu, Tong, Lord, Emma, Masson, Steven, Nunes, Joao, Richardson, Paul, Ryder, Stephen D., Wright, Mark, Thursz, Mark and Vergis, Nikhil
(2023)
In severe alcohol-related hepatitis, acute kidney injury is prevalent, associated with mortality independent of liver disease severity, and can be predicted using IL-8 and micro-RNAs.
Alimentary pharmacology & therapeutics, 58 (11-12), .
(doi:10.1111/apt.17733).
Abstract
Background: the prevalence, prediction and impact of acute kidney injury (AKI) in alcohol-related hepatitis (AH) is uncertain.
Aims: we aimed to determine AKI incidence; association with mortality; evaluate serum biomarkers and the modifying effects of prednisolone and pentoxifylline in the largest AH cohort to date.
Methods: participants in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial with day zero (D0) creatinine available were included. AKI was defined by modified International Club of Ascites criteria; incident AKI as day 7 (D7) AKI without D0-AKI. Survival was compared by Kaplan-Meier; mortality associations by Cox regression; associations with AKI by binary logistic regression; biomarkers by AUROC analyses.
Results: D0-AKI was present in 198/1051 (19%) participants; incident AKI developed in a further 119/571 (21%) with available data. Participants with D0-AKI had higher 90-day mortality than those without (32% vs. 25%, p = 0.008), as did participants with incident AKI compared to those without D0-AKI or incident AKI (47% vs. 25%, p < 0.001). Incident AKI was associated with D90 mortality adjusted for age and discriminant function (AHR 2.15, 1.56-2.97, p < 0.001); D0-AKI was not. Prednisolone therapy reduced incident AKI (AOR 0.55, 0.36-0.85, p = 0.007) but not mortality. D0 bilirubin and IL-8 combined, miR-6826-5p, and miR-6811-3p predicted incident AKI (AUROCs 0.726, 0.821, 0.770, p < 0.01).
Conclusions: incident AKI is associated with 90-day mortality independent of liver function. Prednisolone therapy was associated with reduced incident AKI. IL-8 and several miRNAs are potential biomarkers to predict AKI. Novel therapies to prevent incident AKI should be evaluated in AH to reduce mortality.
Text
Aliment Pharmacol Ther - 2023 - Tyson - In severe alcohol‐related hepatitis acute kidney injury is prevalent associated
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Accepted/In Press date: 18 September 2023
e-pub ahead of print date: 2 October 2023
Published date: December 2023
Additional Information:
Funding Information:
This study was supported by the UK Medical Research Council (grant MR/R014019/1) and the National Institute for Health Research Imperial Biomedical Research Centre. STOPAH was supported by NIHR Health Technology Assessment Programme grant 08/14/44.
Funding Information:
We are grateful for the support of the STOPAH trial management group and the Minimising Mortality from Alcohol‐Related Hepatitis consortium. This study was supported by the UK Medical Research Council (grant MR/R014019/1) and the National Institute for Health Research Imperial Biomedical Research Centre. STOPAH was supported by NIHR Health Technology Assessment Programme grant 08 14 44. We thank Dr. Laura Martinez Gili for her expert advice regarding association testing. This work has been presented at the British Society of Gastroenterology's Annual Meeting and the European Association for the Study of the Liver's International Liver Congress. 49 50
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Local EPrints ID: 484333
URI: http://eprints.soton.ac.uk/id/eprint/484333
ISSN: 0269-2813
PURE UUID: fb287d8a-fd36-40a1-bfe4-f167a28ae1c5
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Date deposited: 15 Nov 2023 18:11
Last modified: 17 Apr 2024 16:31
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Contributors
Author:
Luke D. Tyson
Author:
Stephen Atkinson
Author:
Robert W. Hunter
Author:
Michael Allison
Author:
Andrew Austin
Author:
James W. Dear
Author:
Ewan Forrest
Author:
Tong Liu
Author:
Emma Lord
Author:
Steven Masson
Author:
Joao Nunes
Author:
Paul Richardson
Author:
Stephen D. Ryder
Author:
Mark Wright
Author:
Mark Thursz
Author:
Nikhil Vergis
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