Pathophysiology of hepatic encephalopathy and future treatment options

Rev Gastroenterol Mex (Engl Ed). 2019 Apr-Jun;84(2):195-203. doi: 10.1016/j.rgmx.2019.02.004. Epub 2019 Apr 20.
[Article in English, Spanish]

Abstract

Understanding of the pathophysiology of hepatic encephalopathy has conditioned new treatment options. Ammonia detoxification in hepatic encephalopathy is regulated by two enzymes: glutaminase or glutamine synthetase. The first produces ammonia and the second detoxifies the ammonia, which is why treatments are aimed at glutaminase inhibition or glutamine synthetase activation. At present, we know that both enzymes are found not only in the liver, but also in the muscle, intestine, kidney, and brain. Therefore, current treatments can be directed at each enzyme at different sites. Awareness of those potential treatment sites makes different options of approach possible in the patient with hepatic encephalopathy, and each approach should be personalized.

Keywords: Astrocito; Astrocyte; Detoxificación; Detoxification; Encefalopatía; Encephalopathy; Intestine; Intestino; Kidney; Muscle; Músculo; Riñón.

Publication types

  • Review

MeSH terms

  • Ammonia / metabolism
  • Enzyme Activators / therapeutic use
  • Enzyme Inhibitors / therapeutic use
  • Glutamate-Ammonia Ligase / drug effects
  • Glutaminase / antagonists & inhibitors
  • Hepatic Encephalopathy / physiopathology*
  • Hepatic Encephalopathy / therapy*
  • Humans
  • Hyperammonemia / physiopathology
  • Hyperammonemia / therapy

Substances

  • Enzyme Activators
  • Enzyme Inhibitors
  • Ammonia
  • Glutaminase
  • Glutamate-Ammonia Ligase