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

Authors
  • Jaeger, Victoria1
  • DeMorrow, Sharon2, 3, 4, 5
  • McMillin, Matthew2, 3, 4
  • 1 Baylor Scott & White Health, Department of Internal Medicine, Temple, TX, USA.
  • 2 Texas A&M University Health Science Center, Department of Medical Physiology, Temple, TX, USA.
  • 3 Central Texas Veterans Health Care System, Temple, TX, USA.
  • 4 University of Texas at Austin, Dell Medical School, Department of Internal Medicine, Austin, TX, USA.
  • 5 University of Texas at Austin, College of Pharmacy, Austin, TX, USA.
Type
Published Article
Journal
Journal of clinical and translational hepatology
Publication Date
Dec 28, 2019
Volume
7
Issue
4
Pages
352–361
Identifiers
DOI: 10.14218/JCTH.2019.00025
PMID: 31915605
Source
Medline
Keywords
Language
English
License
Unknown

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. © 2019 Authors.

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