Epigenetic basis for monocyte dysfunction in patients with severe alcoholic hepatitis.

Journal of Hepatology
Laura WeichselbaumStanislas Goriely

Abstract

Severe forms of alcohol-related liver disease are associated with increased susceptibility to infections which are associated with poor prognosis. The cellular and molecular mechanisms responsible for this altered host defense are incompletely understood. We performed whole blood phenotypic analysis and ex vivo stimulation with various pathogen-associated molecular patterns (PAMPs). We included 34 patients with alcohol-related cirrhosis (18 of whom had biopsy-proven severe alcoholic hepatitis [sAH]), 12 healthy controls and 11 patients with chronic alcohol consumption without significant liver disease. We also evaluated the transcriptomic (RNA-seq) and chromatin accessibility (ATAC-seq) profiles of CD14+ monocytes from a subset of patients. Circulating monocytes and conventional dendritic cells (DCs) from patients with sAH displayed complex alterations characterized by increased expression of both activating and inhibitory surface markers and an impaired pro-inflammatory response upon stimulation with PAMPs representative of gram-negative bacteria (lipopolysaccharide, Pam3CSK4) or fungal pathogens (Zymosan). Their decreased ability to produce more than 1 cytokine (polyfunctionality) upon PAMP stimulation correlated with the ris...Continue Reading

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Citations

Nov 19, 2020·JHEP Reports : Innovation in Hepatology·Giacomo ZaccheriniRichard Moreau
Dec 11, 2020·Journal of Hepatology·Vicente ArroyoUNKNOWN investigators from the EASL-CLIF Consortium, Grifols Chair and European Foundation for the Study of Chronic Liver Failure (E
Feb 23, 2021·Frontiers in Immunology·Emmanuel WeissRichard Moreau
May 28, 2021·Journal of Hepatology·Rajiv JalanVicente Arroyo
May 28, 2021·Journal of Hepatology·Schalk Van der MerweAgustin Albillos
Oct 5, 2021·Hepatology International·Hitoshi Maruyama, Shuichiro Shiina

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