Sarcopenia in Chronic Liver Disease: Mechanisms and Countermeasures

Sarcopenia, a condition of low muscle mass, quality and strength, is commonly found in cirrhotic patients and is associated with adverse clinical outcomes including: reduction in quality of life, increased mortality and post-transplant complications. In chronic liver disease (CLD) it 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 a number of 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 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. A number of 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.