Inflammation and hepatic encephalopathy

• Published in: Archives of biochemistry and biophysics 2013-08, Vol.536 (2), p.189-196
• Main Authors: Coltart, Iona, Tranah, Thomas H., Shawcross, Debbie L.
• Format: Article
• Language: English
• Subjects: Ammonia; Ammonia - immunology; Animals; brain; Brain - immunology; Brain - microbiology; Brain - pathology; coma; disease control; encephalopathy; Endotoxemia - complications; Endotoxemia - immunology; Endotoxemia - microbiology; Endotoxemia - therapy; endotoxins; energy; Gastrointestinal Tract - microbiology; Hepatic encephalopathy; Hepatic Encephalopathy - etiology; Hepatic Encephalopathy - immunology; Hepatic Encephalopathy - microbiology; Hepatic Encephalopathy - therapy; homeostasis; Humans; Infection; Inflammation; Inflammation - complications; Inflammation - immunology; Inflammation - microbiology; Inflammation - therapy; Inflammation Mediators - immunology; liver; Liver - immunology; Liver - microbiology; Liver - pathology; Liver Cirrhosis - complications; Liver Cirrhosis - immunology; Liver Cirrhosis - microbiology; Liver Cirrhosis - therapy; nitrogen; pathogenesis; sepsis (infection); Systemic inflammatory response syndrome; Systemic Inflammatory Response Syndrome - complications; Systemic Inflammatory Response Syndrome - immunology; Systemic Inflammatory Response Syndrome - microbiology; Systemic Inflammatory Response Syndrome - therapy; vagus nerve
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2013.03.016

•Hepatic encephalopathy is a neuropsychiatric syndrome associated with liver failure.•The central role of ammonia in its pathogenesis remains incontrovertible.•However there is strong evidence to support inflammation in exacerbating encephalopathy.•Inflammation arises directly in the brain or indirectly in the peripheral circulation.•The relationship between ammonia and inflammation is a synergistic one. Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with both acute and chronic liver dysfunction, spanning a spectrum that ranges from mild neuropsychological disturbances to coma. The central role of ammonia in the pathogenesis of HE remains incontrovertible however, there is a robust evidence base indicating the important role of inflammation in exacerbating the neurological effects of HE. Inflammation can arise directly within the brain itself as a result of deranged nitrogen and energy homeostasis, with resultant neuronal, astrocyte and microglial dysfunction. Inflammation may also originate in the peripheral circulation and exert effects on the brain indirectly, via the release of pro-inflammatory mediators which directly signal to the brain via the vagus nerve. This review summarises the data that demonstrate the synergistic relationship of inflammation and ammonia that culminates in the manifestation of HE. Sterile inflammation arising from the inflamed or necrotic liver, circulating endotoxin arising from the gut (bacterial translocation) inducing immune dysfunction, and superimposed sepsis will be comprehensively discussed. Finally, this review will provide an overview of the existing and novel treatments on the horizon which can target the inflammatory response, and how they might translate into clinical practise as therapies in the prophylaxis and treatment of HE.