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

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...

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Detalles Bibliográficos
Autores: Ventura-Cots, M, Argemi, J, Jones, PD, Lackner, C, El Hag, 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, Degre, 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, VJ, Shawcross, DL, Stauber, RE, Straub, BK, Verna, E, Tiniakos, D, Trepo, E, Vargas, V, Villanueva, C, Woosley, JT, Ziol, M, Mueller, S, Starkel, P, Bataller, R
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p6267
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6267
https://eprints.ncl.ac.uk/279795
Access Level:acceso abierto
Palabra clave:alcohol liver disease
clinical trial
fibrosis
human
liver
metabolism
multicenter study
pathology
prospective study
retrospective study
Fibrosis
Hepatitis, Alcoholic
Humans
Liver
Prospective Studies
Retrospective Studies
Descripción
Sumario: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) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

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