Susceptibility to Infection in Liver Failure

The leading cause of death in patients with end stage liver disease including acute alcoholic hepatitis (AAH) is the development of sepsis. Recurrence of acute infections in this patient group is increasingly common and is ultimately responsible for the development of multiple organ failure. This susceptibility to sepsis is thought to be as a consequence of neutrophil dysfunction and this has been clinically documented in patients with acute liver failure.

All investigations to date have focussed on the functions of peripheral neutrophils and there is a paucity of knowledge regarding the interactions between neutrophils and the liver. No treatment strategies are yet available to restore functional and appropriate neutrophil responses.

Current Research

Neutrophil dysfunction in a novel in vitro model of acute liver injury

In order to understand the mechanisms involved in neutrophil dysfunction in alcohol-related liver disease we have established a novel in vitro model to investigate the particular role of alcohol on normal neutrophil functions when co-cultured either directly or indirectly with liver cells (hepatocytes), using both a neutrophil cell line (HL60) and neutrophils isolated from control donor blood. In particular, we are looking at the role of alcohol on phagocytosis, oxidative burst, surface markers, Toll-like receptor expression, cytokine production and intracellular signalling proteins.

Preliminary studies have shown that alcohol appears to impair neutrophil function directly but this dysfunction is profoundly increased after alcohol has been metabolised by hepatocytes implicating a causal link between liver injury and impairment of antibacterial neutrophil functions.

Published by: Foundation for Liver Research

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