Journal
WORLD JOURNAL OF GASTROENTEROLOGY
Volume 21, Issue 42, Pages 11904-11913Publisher
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.3748/wjg.v21.i42.11904
Keywords
Alcoholic hepatitis; Alcoholic liver disease; Toll-like receptors; Gut dysbiosis; T cell exhaustion
Categories
Funding
- National Institute for Health Research [CL-2014-24-001] Funding Source: researchfish
Ask authors/readers for more resources
Acute alcoholic hepatitis (AAH) is a serious complication of alcohol misuse and has high short term mortality. It is a clinical syndrome characterised by jaundice and coagulopathy in a patient with a history of recent heavy alcohol use and is associated with profound immune dysfunction with a primed but ineffective immune response against pathogens. Here, we review the current knowledge of the pathogenesis and immune defects of AAH and identify areas requiring further study. Alcohol activates the immune system primarily through the disruption of gut tight junction integrity allowing the escape of pathogen-associated molecular particles (PAMPs) into the portal venous system. PAMPs stimulate cells expressing toll-like receptors (mainly myeloid derived cells) and initiate a network of intercellular signalling by secretion of many soluble mediators including cytokines and chemokines. The latter coordinates the infiltration of neutrophils, monocytes and T cells and results in hepatic stellate cell activation, cellular damage and hepatocyte death by necrosis or apoptosis. On the converse of this immune activation is the growing evidence of impaired microbial defence. Neutrophils have reduced phagocytic capacity and oxidative burst and there is recent evidence that T cell exhaustion plays a role in this.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available