Role of circadian rhythm and autonomic nervous system in liver function: a hypothetical basis for improving the management of hepatic encephalopathy

Am J Physiol Gastrointest Liver Physiol. 2021 Oct 1;321(4):G400-G412. doi: 10.1152/ajpgi.00186.2021. Epub 2021 Aug 4.

Abstract

Hepatic encephalopathy (HE) is a common, incapacitating complication of cirrhosis that affects many patients with cirrhosis. Although several therapies have proven effective in the treatment and prevention of this condition, several patients continue to suffer from covert disease or episodes of relapse. The circadian rhythm has been demonstrated to be pivotal for many body functions, including those of the liver. Here, we explore the impact of circadian rhythm-dependent signaling on the liver and discuss the evidence of its impact on liver pathology and metabolism. We describe the various pathways through which circadian influences are mediated. Finally, we introduce a novel method for improving patient response to drugs aimed at treating HE by utilizing the circadian rhythm. A digital system that introduces a customization-based technique for improving the response to therapies is presented as a hypothetical approach for improving the effectiveness of current medications used for the treatment of recurrent and persistent hepatic encephalopathy.

Keywords: chronotherapy; circadian rhythm; digital system; encephalopathy; hepatic encephalopathy.

Publication types

  • Review

MeSH terms

  • Animals
  • Autonomic Nervous System / physiology*
  • Circadian Rhythm*
  • Gastrointestinal Agents / therapeutic use
  • Hepatic Encephalopathy / drug therapy*
  • Hepatic Encephalopathy / metabolism
  • Humans
  • Liver / metabolism*
  • Liver / physiology
  • Liver / physiopathology

Substances

  • Gastrointestinal Agents