Emerging Treatment Options for Sarcopenia in Chronic Liver Disease

Abstract

Sarcopenia is characterized by a skeletal muscle disorder with progressive and generalized loss of muscle mass and function, and it increases the risk of adverse outcomes with considerable prevalence in patients with chronic liver disease. Sarcopenia in chronic liver disease underlies complicated and multifactorial mechanisms for pathogenesis, including alterations in protein turnover, hyperammonemia, energy disposal, hormonal changes, and chronic inflammation. The key contribution to sarcopenia in patients with chronic liver diseases can be the hyperammonemia-induced upregulation of myostatin, which causes muscle atrophy via the expression of atrophy-related genes. Several clinical studies on emerging treatment options for sarcopenia have been reported, but only a few have focused on patients with chronic liver diseases, with mostly nutritional and behavioral interventions being carried out. The inhibition of the myostatin-activin receptor signaling pathway and hormonal therapy might be the most promising therapeutic options in combination with an ammonia-lowering approach in sarcopenic patients with chronic liver diseases. This review focuses on current and emerging treatment options for sarcopenia in chronic liver diseases with underlying mechanisms to counteract this condition.

Sarcopenia in the Cirrhotic Patient: Current Knowledge and Future Directions

“…Myostatin, as briefly stated, is a protein secreted by muscle cells that inhibits muscle synthesis and differentiation and promotes muscle degradation [24,85] . It is primarily activated by elevated ammonia levels precipitated by cirrhosis, J o u r n a l P r e -p r o o f though other stimuli include decreased testosterone and increased TNF-α [24] .…”

Sarcopenia in Chronic Liver Disease: A Metabolic Perspective

“…stamulumab, landogrozumab, and trevogrumab) are now being investigated for their safety and efficacy. 122 Furthermore, glucose-lowering medications such as metformin and thiazolidinedione have been shown to improve skeletal muscle mass, strength, and performance in diabetes patients, indicating the need for their evaluation in a long-term, well-designed study in CLD patients.…”

Clinical Nutrition: Recent Advances and Remaining Challenges

“…Additional supplementation is currently only recommended in cases of confirmed or clinically suspected deficiency. Data on zinc supplementation is conflicting: some studies report positive effects on zinc supplementation in hepatic encephalopathy [180][181][182], while others report no significant improvements [183,184]. Zinc supplementation in case of deficiency improves liver function and nutritional status [185,186] and may even impact positively on clinical outcome [187,188].…”