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Clinical, histological and molecular profiling of different stages of alcohol-related liver disease

Lookup NU author(s): Dr Steven MassonORCiD, Dr Dina Tiniakos

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


Abstract

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.


Publication metadata

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

Pages: epub ahead of print

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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