Published online Nov 14, 2015. doi: 10.3748/wjg.v21.i42.11904
Peer-review started: April 15, 2015
First decision: May 18, 2015
Revised: June 3, 2015
Accepted: September 30, 2015
Article in press: September 30, 2015
Published online: November 14, 2015
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.
Core tip: Acute alcoholic hepatitis (AAH) has high short-term mortality and is challenging to treat with only glucocorticoids demonstrating proven survival benefit. Development of other effective treatment requires a clear understanding of the mechanisms of immune dysfunction in AAH. Here, we review recent progress in the field and identify areas in need of further research; particularly the role of gut dysbiosis in allowing presentation of pathogen associated molecular patterns to innate receptors on myeloid cells and the subsequent recruitment of immune cell subsets. Recent data demonstrating that T cells have an exhausted phenotype and result in impaired antimicrobial defence is also discussed.