Pathophysiology of Hepatic Encephalopathy

Clin Liver Dis. 2020 May;24(2):175-188. doi: 10.1016/j.cld.2020.01.002. Epub 2020 Feb 19.

Abstract

Hepatic encephalopathy (HE) is one of the major clinical decompensations of cirrhosis, with a high impact on health care resource utilization and cost. For an effective and comprehensive management of HE, the clinicians need to understand the pathophysiologic mechanisms of HE. This review describes the multiorgan processes involved in HE and how several HE precipitants and treatment strategies act on ammonia production, excretion, and neurotoxicity, including the impact of diabetes and use of cannabinoids. The authors also discuss the current and future role of gut microbiome, systemic/central inflammation, and various neurotransmitters for the pathogenesis and treatment of HE.

Keywords: Ammonia; Cannabinoids; Gut-liver-brain axis; Hepatic encephalopathy; Liver cirrhosis; Neurotoxicity; Neurotransmitters; TNF-Alpha.

Publication types

  • Review

MeSH terms

  • Ammonia / blood
  • Ammonia / metabolism*
  • Animals
  • Astrocytes / physiology*
  • Diabetes Complications / complications
  • Gastrointestinal Microbiome
  • Glutamic Acid / metabolism
  • Glutamine / metabolism
  • Hepatic Encephalopathy / blood
  • Hepatic Encephalopathy / etiology*
  • Hepatic Encephalopathy / metabolism*
  • Histamine / metabolism
  • Humans
  • Inflammation / blood
  • Liver Cirrhosis / complications
  • Manganese / metabolism
  • Microglia / physiology
  • Oxidative Stress
  • Serotonin / metabolism
  • Tumor Necrosis Factor-alpha / blood
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Tumor Necrosis Factor-alpha
  • Glutamine
  • Serotonin
  • Glutamic Acid
  • Manganese
  • gamma-Aminobutyric Acid
  • Ammonia
  • Histamine