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

Meritxell Ventura-Cots, Josepmaria Argemi, Patricia D. Jones, Carolin Lackner, Mohamed El Hag, Juan G. Abraldes, Edilmar Alvarado, Ana Clemente, Samitha Ravi, Antonio Alves, Mohamed Alboraie, Jose Altamirano, Sergio Barace, Francisco Bosques, Robert Brown, Juan Caballeria, Joaquin Cabezas, Sofia Carvalhana, Helena Cortez-Pinto, Adilia CostaDelphine Degré, Carlos Fernandez-Carillo, Nathalie Ganne-Carrie, Guadalupe Garcia-Tsao, Joan Genesca, John Koskinas, Nicolas Lanthier, Alexandre Louvet, Juan José Lozano, Michael R. Lucey, Steven Masson, Philippe Mathurin, Nahum Mendez-Sanchez, Rosa Miquel, Christophe Moreno, Taofic Mounajjed, Gemma Odena, Won Kim, Pau Sancho-Bru, R. Warren Sands, Justyna Szafranska, Laurine Verset, Bern Schnabl, Christine Sempoux, Vijay Shah, Debbie Lindsay Shawcross, Rudolf E. Stauber, Beate K. Straub, Elizabeth Verna, Dina Tiniakos, Eric Trépo, Victor Vargas, Càndid Villanueva, John T. Woosley, Marianne Ziol, Sebastian Mueller, Peter Stärkel, Ramon Bataller

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish
Article number324295
JournalGut
DOIs
StatePublished - 1 Sep 2022
Externally publishedYes

Keywords

  • alcohol
  • alcohol-induced injury
  • alcoholic liver disease
  • gene expression
  • histopathology

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