Journal of Clinical and Translational Hepatology

Journal of Clinical and Translational Hepatology

Monday, 03 / 30 / 2020

Articles

The Direct Contribution of Astrocytes and Microglia to the Pathogenesis of Hepatic Encephalopathy

REVIEW ARTICLE

The Direct Contribution of Astrocytes and Microglia to the Pathogenesis of Hepatic Encephalopathy

Victoria Jaeger1, Sharon DeMorrow2,3,4,5 and Matthew McMillin*,2,3,4

1Baylor Scott & White Health, Department of Internal Medicine, Temple, TX, USA
2Texas A&M University Health Science Center, Department of Medical Physiology, Temple, TX, USA
3Central Texas Veterans Health Care System, Temple, TX, USA
4University of Texas at Austin, Dell Medical School, Department of Internal Medicine, Austin, TX, USA
5University of Texas at Austin, College of Pharmacy, Austin, TX, USA

*Correspondence to: Matthew McMillin, University of Texas at Austin Dell Medical School, 1601 Trinity Street, Building B, Austin, TX 78701, USA. Tel: +1-512-495-5037, Fax: +1-512-495-5839, E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Journal of Clinical and Translational Hepatology 2019;7(4):352-361 DOI: 10.14218/JCTH.2019.00025
Received: July 5, 2019 Accepted: October 24, 2019 Published online: November 13, 2019

Abstract

Hepatic encephalopathy is a neurological complication resulting from loss of hepatic function and is associated with poor clinical outcomes. During acute liver failure over 20% of mortality can be associated with the development of hepatic encephalopathy. In patients with liver cirrhosis, 1-year survival for those that develop overt hepatic encephalopathy is under 50%. The pathogenesis of hepatic encephalopathy is complicated due to the multiple disruptions in homeostasis that occur following a reduction in liver function. Of these, elevations of ammonia and neuroinflammation have been shown to play a significant contributing role to the development of hepatic encephalopathy. Disruption of the urea cycle following liver dysfunction leads to elevations of circulating ammonia, which enter the brain and disrupt the functioning of astrocytes. This results in dysregulation of metabolic pathways in astrocytes, oxidative stress and cerebral edema. Besides ammonia, circulating chemokines and cytokines are increased following liver injury, leading to activation of microglia and a subsequent neuroinflammatory response. The combination of astrocyte dysfunction and microglia activation are significant contributing factors to the pathogenesis of hepatic encephalopathy.

Keywords

Acute liver failure, Microglia, Neuroinflammation, Ammonia, Astroglia

 

 

 

Journal of Clinical and Translational Hepatology 2019 vol. 7, 352-361  [ Html ] [ PDF Full-text ]

© The Authors 2019. This article is published under the terms of the Creative Commons Attribution-Noncommercial License (CC BY-NC 4.0), which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non-commercial and is otherwise in compliance with the license.

 

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