title: Immune dysfunction in acute alcoholic hepatitis.
abstract: 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.affiliation: Ashwin D Dhanda, Peter L Collins, School of Clinical Sciences, University of Bristol, BS2 8HW Bristol, United Kingdom.
authors.forename: Ashwin D
authors.initials: AD
authors.lastname: Dhanda
authors.affiliation: Ashwin D Dhanda, Peter L Collins, School of Clinical Sciences, University of Bristol, BS2 8HW Bristol, United Kingdom.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
mesh_terms: D000208:Acute Disease; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000401:mortality; D000818:Animals; D018988:Bacterial Translocation; D018925:Chemokines / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology; D006519:Hepatitis, Alcoholic / Q000175:diagnosis / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D006801:Humans; D018928:Immunity, Mucosal; D018836:Inflammation Mediators / Q000276:immunology; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D008099:Liver / Q000276:immunology* / Q000473:pathology; D011379:Prognosis; D012307:Risk Factors; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D018925:Chemokines; D018836:Inflammation Mediators; D051193:Toll-Like Receptors; D016179:Granulocyte Colony-Stimulating Factor
keywords: Alcoholic hepatitis; Alcoholic liver disease; Gut dysbiosis; T cell exhaustion; Toll-like receptors