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Project

Deciphering the molecular pathways needed to restore monocyte dysfunction during Acute-on-chronic liver failure

Acute-on-chronic liver failure (ACLF) is characterized by a rapid deterioration of liver function and organ failure. This syndrome is a devastating clinical entity, associated with extremely low patient survival (28-day mortality rate 30-40%). A paralysis of the immune system and susceptibility to infections often precipitate this syndrome and there are currently no targeted strategies to combat these complications in ACLF patients. Importantly, circulating monocytes are crucial cellular components of the host defense system against invading pathogens and monocytes from ACLF patients have already been shown to exhibit a defective antimicrobial function. Here we aim to perform a comprehensive transcriptional and metabolic characterization of monocyte function in ACLF patients and integrate these different aspects into a model for target identification aiming at restoring their function back to normal. A better definition of how the gene expression, metabolic and functional activities of monocytes are regulated in ACLF patients can provide valuable insight into fundamental disease mechanisms and their possible therapeutic targeting.
Date:1 Oct 2018 →  30 Sep 2022
Keywords:Acute-on-chronic liver failure, alcohol-related cirrhosis, Immune dysfunction, Monocytes, Innate immunity, Immunometabolism
Disciplines:Immunology, Gastro-enterology and hepatology, Paediatrics and neonatology, Nursing