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Lookup NU author(s): Dr Steven MassonORCiD, Dr Dina Tiniakos
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
Objective: Alcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking.Design: Two large cohorts of patients were recruited in an international, observational multicentre study: a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225). Clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis of both disease phenotypes were performed.Results: Age and mean alcohol intake were similar in both groups. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma-glutamyl transferase levels than in ndALD patients. Patients with AH demonstrated profound liver failure and increased mortality. One-year mortality was 10% in ndALD and 50% in AH. Histologically, steatosis grade, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and ductular reaction were more frequent among AH patients. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. While ndALD was characterised by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism.Conclusions: Despite comparable alcohol intake, AH patients presented with worse liver function compared with ndALD patients. Bilirubinostasis, severe fibrosis and ductular reaction were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared with ndALD patients.
Author(s): Ventura-Cots M, Argemi J, Jones PD, Lackner C, Elhag M, Abraldes JG, Alvarado E, Clemente A, Ravi S, Alves A, Alboraie M, Altamirano J, Barace S, Bosques F, Brown R, Caballeria J, Cabezas J, Carvalhana S, Cortez-Pinto H, Costa A, Degré D, Fernandez-Carillo C, Ganne-Carrie N, Garcia-Tsao G, Genesca J, Koskinas J, Lanthier N, Louvet A, Lozano JJ, Lucey MR, Masson S, Mathurin P, Mendez-Sanchez N, Miquel R, Moreno C, Mounajjed T, Odena G, Kim W, Sancho-Bru P, Sands RW, Szafranska J, Verset L, Schnabl B, Sempoux C, Shah V, Shawcross DL, Stauber R, Straub BK, Verna E, Tiniakos D, Trépo E, Vargas V, Villanueva C, Woosley J, Ziol M, Mueller S, Stärkel P, Bataller R
Publication type: Article
Publication status: Published
Journal: Gut
Year: 2022
Volume: 71
Issue: 9
Pages: 1856-1866
Print publication date: 01/09/2022
Online publication date: 06/01/2022
Acceptance date: 06/12/2021
Date deposited: 29/01/2022
ISSN (print): 0017-5749
ISSN (electronic): 1468-3288
Publisher: BMJ Group
URL: https://doi.org/10.1136/gutjnl-2021-324295
DOI: 10.1136/gutjnl-2021-324295
PubMed id: 34992134
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