Title :

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

Author(s) :

Ventura-Cots, M. [Auteur]
Argemi, J. [Auteur]
Jones, P. D. [Auteur]
Lackner, C. [Auteur]
El Hag, M. [Auteur]
Abraldes, J. G. [Auteur]
Alvarado, E. [Auteur]
Clemente, A. [Auteur]
Ravi, S. [Auteur]
Alves, A. [Auteur]
Alboraie, M. [Auteur]
Altamirano, J. [Auteur]
Barace, S. [Auteur]
Bosques, F. [Auteur]
Brown, R. [Auteur]
Caballeria, J. [Auteur]
Cabezas, J. [Auteur]
Carvalhana, S. [Auteur]
Cortez-Pinto, H. [Auteur]
Costa, A. [Auteur]
Degré, Delphine [Auteur]
Centre de Ressources Biologiques [Paris]
Fernandez-Carillo, C. [Auteur]
Ganne-Carrie, Nathalie [Auteur]
Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] [FunGeST]
Garcia-Tsao, G. [Auteur]
Genesca, J. [Auteur]
Koskinas, J. [Auteur]
Lanthier, N. [Auteur]
Louvet, Alexandre [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Lozano, J. J. [Auteur]
Lucey, M. R. [Auteur]
Masson, S. [Auteur]
Mathurin, Philippe [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Mendez-Sanchez, N. [Auteur]
Miquel, R. [Auteur]
Moreno, C. [Auteur]
Mounajjed, T. [Auteur]
Odena, G. [Auteur]
Kim, W. [Auteur]
Sancho-Bru, P. [Auteur]
Warren Sands, R. [Auteur]
Szafranska, J. [Auteur]
Verset, L. [Auteur]
Schnabl, B. [Auteur]
Sempoux, C. [Auteur]
Shah, V. [Auteur]
Shawcross, D. L. [Auteur]
Stauber, R. E. [Auteur]
Straub, B. K. [Auteur]
Verna, E. [Auteur]
Tiniakos, D. [Auteur]
Trépo, E. [Auteur]
Vargas, V. [Auteur]
Villanueva, C. [Auteur]
Woosley, J. T. [Auteur]
Ziol, Marianne [Auteur]
Centre de Ressources Biologiques [Paris]
Mueller, S. [Auteur]
Stärkel, P. [Auteur]
Bataller, R. [Auteur]

Journal title :

Gut

Abbreviated title :

Gut

Publication date :

2022-01-09

ISSN :

1468-3288

English keyword(s) :

alcohol
alcoholic liver disease
histopathology
gene expression
alcohol-induced injury

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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, ...
Show more >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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Submission date :

2024-01-12T05:13:53Z
2024-03-19T14:22:46Z