Sarcopenia in chronic liver disease: mechanisms and countermeasures

Am J Physiol Gastrointest Liver Physiol. 2021 Mar 1;320(3):G241-G257. doi: 10.1152/ajpgi.00373.2020. Epub 2020 Nov 25.


Sarcopenia, a condition of low muscle mass, quality, and strength, is commonly found in patients with cirrhosis and is associated with adverse clinical outcomes including reduction in quality of life, increased mortality, and posttransplant complications. In chronic liver disease (CLD), sarcopenia is most commonly defined through the measurement of the skeletal muscle index of the third lumbar spine. A major contributor to sarcopenia in CLD is the imbalance in muscle protein turnover, which likely occurs due to a decrease in muscle protein synthesis and an elevation in muscle protein breakdown. This imbalance is assumed to arise due to several factors including accelerated starvation, hyperammonemia, amino acid deprivation, chronic inflammation, excessive alcohol intake, and physical inactivity. In particular, hyperammonemia is a key mediator of the liver-gut axis and is known to contribute to mitochondrial dysfunction and an increase in myostatin expression. Currently, the use of nutritional interventions such as late-evening snacks, branched-chain amino acid supplementation, and physical activity have been proposed to help the management and treatment of sarcopenia. However, little evidence exists to comprehensively support their use in clinical settings. Several new pharmacological strategies, including myostatin inhibition and the nutraceutical Urolithin A, have recently been proposed to treat age-related sarcopenia and may also be of use in CLD. This review highlights the potential molecular mechanisms contributing to sarcopenia in CLD alongside a discussion of existing and potential new treatment strategies.

Keywords: chronic liver disease; exercise; muscle protein synthesis; nutrition; sarcopenia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Energy Metabolism
  • Humans
  • Liver Diseases / complications*
  • Liver Diseases / metabolism
  • Liver Diseases / pathology
  • Proteostasis
  • Sarcopenia / complications*
  • Sarcopenia / metabolism
  • Sarcopenia / pathology
  • Sarcopenia / therapy