Treatment to improve nutrition and functional capacity evaluation in liver transplant candidates.

OPINION STATEMENT: Liver transplantation is the definitive therapy for cirrhosis, and malnutrition is the most frequent complication in these patients. Sarcopenia or loss of muscle mass is the major component of malnutrition in cirrhotics and adversely affects their outcome. In addition to the metabolic consequences, functional consequences of sarcopenia include reduced muscle strength and deconditioning. Despite nearly universal occurrence of sarcopenia and its attendant complications, there are no established therapies to prevent or reverse the same. Major reasons for this deficiency include the lack of established standardized definitions or measures to quantify muscle mass, as well as paucity of mechanistic studies or identified molecular targets to develop specific therapeutic interventions. Anthropometric evaluation, bioelectrical impedance analysis, and DEXA scans are relatively imprecise measures of muscle mass, and recent data on imaging measures to determine muscle mass accurately are likely to allow well-defined outcome responses to treatments. Resurgence of interest in the mechanisms of muscle loss in liver disease has been directly related to the rapid advances in the field of muscle biology. Metabolic tracer studies on whole body kinetics have been complemented by direct studies on the skeletal muscle of cirrhotics. Hypermetabolism and anabolic resistance contribute to sarcopenia. Reduced protein synthesis and increased autophagy have been reported in cirrhotic skeletal muscle, while the contribution of the ubiquitin-proteasome pathway is controversial. Increased plasma concentration and skeletal muscle expression of myostatin, a TGFβ superfamily member that causes reduction in muscle mass, have been reported in cirrhosis. Hyperammonemia and TNFα have been reported to increase myostatin expression and may be responsible for sarcopenia in cirrhosis. Nutriceutical interventions with leucine enriched amino acid mixtures, myostatin antagonists and physical activity hold promise as measures to reverse sarcopenia. There is even less data on muscle function and deconditioning in cirrhosis and studies in this area are urgently needed. Even though macronutrient replacement is a major therapeutic goal, micronutrient supplementation, specifically vitamin D, is expected to improve outcomes.