Sarcopenia: Ammonia metabolism and hepatic encephalopathy

Clin Mol Hepatol. 2019 Sep;25(3):270-279. doi: 10.3350/cmh.2019.0015. Epub 2019 Apr 22.

Abstract

Sarcopenia (loss of muscle mass and/or strength) frequently complicates liver cirrhosis and adversely affects the quality of life; cirrhosis related liver decompensation and significantly decreases wait-list and post-liver transplantation survival. The main therapeutic strategies to improve or reverse sarcopenia include dietary interventions (supplemental calorie and protein intake), increased physical activity (supervised resistance and endurance exercises), hormonal therapy (testosterone), and ammonia lowering agents (L-ornithine L-aspartate, branch chain amino acids) as well as mechanistic approaches that target underlying molecular and metabolic abnormalities. Besides other factors, hyperammonemia has recently gained attention and increase sarcopenia by various mechanisms including increased expression of myostatin, increased phosphorylation of eukaryotic initiation factor 2a, cataplerosis of α ketoglutarate, mitochondrial dysfunction, increased reactive oxygen species that decrease protein synthesis and increased autophagy-mediated proteolysis. Sarcopenia contributes to frailty and increases the risk of minimal and overt hepatic encephalopathy.

Keywords: Ammonia; Hepatic encephalopathy; Liver cirrhosis; Sarcopenia; Testosterone.

Publication types

  • Review

MeSH terms

  • Ammonia / metabolism*
  • Exercise Therapy
  • Follistatin / therapeutic use
  • Hepatic Encephalopathy / complications
  • Hepatic Encephalopathy / pathology*
  • Humans
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / pathology
  • Muscle Proteins / antagonists & inhibitors
  • Muscle Proteins / biosynthesis
  • Muscle, Skeletal / metabolism
  • Sarcopenia / complications
  • Sarcopenia / pathology*
  • Sarcopenia / therapy
  • Testosterone / blood
  • Testosterone / therapeutic use

Substances

  • Follistatin
  • Muscle Proteins
  • Testosterone
  • Ammonia