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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2015; 21(42): 11904-11913
Published online Nov 14, 2015. doi: 10.3748/wjg.v21.i42.11904
Immune dysfunction in acute alcoholic hepatitis
Ashwin D Dhanda, Peter L Collins
Ashwin D Dhanda, Peter L Collins, School of Clinical Sciences, University of Bristol, BS2 8HW Bristol, United Kingdom
Ashwin D Dhanda, NIHR Academic Clinical Lecturer in Hepatology, Institute of Translational and Stratified Medicine, Plymouth University Peninsula Schools of Medicine and Dentistry, PL6 8BU Plymouth, United Kingdom
Ashwin D Dhanda, South West Liver Unit, Plymouth Hospitals NHS Trust, PL6 8BU Plymouth, United Kingdom
Peter L Collins, Department of Liver Medicine, University Hospitals Bristol NHS Foundation Trust, BS2 8HW Bristol, United Kingdom
Author contributions: Dhanda AD wrote the paper; Collins PL revised the paper.
Conflict-of-interest statement: Both authors declare that no conflict of interest exists.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Ashwin D Dhanda, MRCP, PhD, NIHR Academic Clinical Lecturer in Hepatology, Institute of Translational and Stratified Medicine, Plymouth University Peninsula Schools of Medicine and Dentistry, John Bull Building, Research Way, Devon, PL6 8BU Plymouth, United Kingdom.
Telephone: +44-1752-437444
Received: April 13, 2015
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.

Keywords: Alcoholic hepatitis, Alcoholic liver disease, Toll-like receptors, Gut dysbiosis, T cell exhaustion

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.