Current management strategies for sarcopenia and frailty in cirrhosis: Missing link in transplant candidacy

Abstract

Sarcopenia and frailty are pervasive, interrelated syndromes in cirrhosis that worsen morbidity, quality of life, transplantation waitlist outcomes, and post-transplant survival. This review synthesized contemporary evidence on definitions, epidemiology, mechanisms, diagnosis, prognostic impact, and management with an emphasis on implementable strategies in hepatology practice. Sarcopenia affects 40%-70% of patients with cirrhosis, and frailty affects 20%-50% of patients with cirrhosis with variations across populations and definitions. Mechanistic drivers include hyperammonemia, systemic inflammation, endocrine disturbances, malnutrition and accelerated starvation, gut-liver-muscle axis alterations, mammalian target of rapamycin inhibition, and inactivity. Diagnosis spans simple bedside tests such as handgrip strength, chair stands, gait speed, and the Liver Frailty Index as well as imaging modalities including computed tomography-based skeletal muscle index, dual energy X-ray absorptiometry, magnetic resonance imaging, and bioimpedance. Both sarcopenia and frailty independently predict hepatic decompensation, hospitalizations, waitlist dropout, and mortality, providing additive prognostic value beyond model for end-stage liver disease (MELD)/MELD-Na, and they are associated with longer intensive care unit and hospital stays and worse post-transplant outcomes. Management requires a multimodal approach: Optimization of cirrhosis complications and ammonia-lowering therapy; adequate nutrition with 1.2-1.5 g/kg/day protein and a late-evening snack; structured aerobic and resistance exercise programs; cautious use of testosterone in hypogonadal males; and emerging therapies such as beta-hydroxy-beta-methylbutyrate, vitamin D, L-carnitine, microbiome modulation, and myostatin inhibitors. Routine screening and multidisciplinary prehabilitation should be embedded in standard care pathways, and incorporation of sarcopenia and frailty metrics alongside MELD may refine risk stratification, enhance transplant allocation, and improve long-term outcomes.

Keywords: Cirrhosis; Sarcopenia; Frailty; Liver transplant; Malnutrition; Hyperammonemia; Exercise therapy; Branched-chain amino acids

Core Tip: Sarcopenia and frailty are under-recognized yet powerful predictors of outcomes in cirrhosis, influencing decompensation, hospitalizations, transplantation waitlist dropout, and post-transplant survival independent of the model for end-stage liver disease score. Simple bedside tools such as handgrip strength, chair stands, gait speed, and the Liver Frailty Index as well as imaging-based skeletal muscle measures enable early recognition. Incorporating routine assessment and structured prehabilitation, including adequate nutrition, resistance and aerobic exercise, and management of cirrhosis complications, can improve quality of life, reduce adverse outcomes, and optimize transplant candidacy.