Sarcopenia and Skeletal Muscle Dysfunction in Liver Cirrhosis: Clinical Perspectives of Myostatin Inhibition

Liver cirrhosis is frequently complicated by sarcopenia, a progressive and systemic loss of skeletal muscle mass and function that contributes substantially to increased morbidity, mortality, and healthcare utilisation. The pathogenesis of sarcopenia in cirrhosis is multifactorial, involving hyperammonaemia, altered protein turnover, hormonal and cytokine dysregulation, chronic inflammation, malnutrition, and broader metabolic disturbances. Increasing evidence suggests that these convergent pathological processes are mediated, at least in part, through dysregulation of myokine signalling pathways, particularly those involving myostatin. Myostatin, in concert with downstream effectors such as mechanistic target of rapamycin (mTOR), plays a central role not only in skeletal muscle homeostasis but also in systemic metabolic regulation, highlighting its relevance beyond muscle biology alone. Therapeutic strategies targeting myostatin signalling have been developed, with several myostatin inhibitors advancing into clinical trials. Emerging data indicate that these agents may increase skeletal muscle mass, reduce adiposity, and improve glucose metabolism in patients with sarcopenia and other metabolic disorders, supporting their pleiotropic metabolic effects. However, the mechanistic role and therapeutic implications of myostatin modulation in the specific context of coexisting cirrhosis and sarcopenia remain incompletely understood. This review summarises current knowledge on myokine-mediated regulation of muscle metabolism in cirrhosis, with a focus on the myostatin–mTOR axis. We critically evaluate existing and emerging myostatin-targeting approaches, including pharmacological inhibition and gene-based therapies, as potential strategies to restore muscle mass and function. Finally, we outline future directions for translational research aimed at modulating myostatin signalling in cirrhosis-associated sarcopenia, emphasising the need to elucidate its systemic metabolic effects to identify novel therapeutic targets and improve clinical outcomes in this population.