Posttransplant Sarcopenia: An Underrecognized Early Consequence of Liver Transplantation

Abstract

Liver transplantation is believed to reverse the clinical and metabolic abnormalities of cirrhosis. Reduced skeletal muscle mass or sarcopenia contributes to increased mortality and adverse consequences of cirrhosis. Failure of reversal of sarcopenia of cirrhosis after liver transplantation is not well recognized. Six temporally, geographically, and methodologically distinct follow-up studies in 304 cirrhotics reported conflicting data on changes in indirect measures of skeletal muscle mass after transplantation. Distinct measures of body composition but not skeletal muscle mass were used and did not focus on the clinical consequences of sarcopenia after transplantation. A number of studies reported an initial rapid postoperative loss of lean mass followed by incomplete recovery with a maximum follow-up of 2 years. Posttransplant sarcopenia may be responsible for metabolic syndrome and impaired quality of life after liver transplantation. Potential reasons for failure to reverse sarcopenia after liver transplantation include use of immunosuppressive agents [mammalian target of rapamycin (mTOR) and calcineurin inhibitors] that impair skeletal muscle growth and protein accretion. Repeated hospitalizations, posttransplant infections, and renal failure also contribute to posttransplant sarcopenia. Finally, recovery from muscle deconditioning is limited by lack of systematic nutritional and physical-activity-based interventions to improve muscle mass. Despite the compelling data on sarcopenia before liver transplantation, the impact of posttransplant sarcopenia on clinical outcomes is not known. There is a compelling need for studies to examine the mechanisms and consequences of sarcopenia post liver transplantation to permit development of therapies to prevent and reverse this disorder.

Factors Associated With Changes in Body Composition Shortly After Orthotopic Liver Transplantation

“…The effects of tacrolimus on skeletal muscle are better described, because the majority of studies have exclusively 6,7 or nearly exclusively 13 used tacrolimus as the immunosuppressive agent. 11,36 Accordingly, despite the lack of significant changes in the REE, our patients on the tacrolimus-based regimen exhibited no muscle catch-up during the study period. 11,36 Accordingly, despite the lack of significant changes in the REE, our patients on the tacrolimus-based regimen exhibited no muscle catch-up during the study period.…”

“…39,40 The insulin resistance induced by these drugs has been reported to be different after kidney transplantation. These findings may be attributable to our short-term follow-up, because the steroid dose has been described as risk factor for a decrease in LM 11,20 due to the increase in proteolysis and impairment in protein synthesis that are mediated by myostatin [44][45][46][47] and the risk for fat deposition that results from increased appetite and decreased fat oxidation. 34,41 Insulin resistance has well-known effects on skeletal muscle and adipose tissue metabolism.…”

“…10,11 Immunosuppressive agents, in general, may be responsible for the persistence of overhydrated fat-free mass, which in turn is related to increased extracellular water. 10,11 Immunosuppressive agents, in general, may be responsible for the persistence of overhydrated fat-free mass, which in turn is related to increased extracellular water.…”

Change in skeletal muscle mass after administering entecavir in patients with hepatitis B

“…The present study showed that skeletal muscle mass increases in parallel with a rise in serum Alb. Increases in skeletal muscle mass from therapeutic interventions have been observed after liver transplant and transjugular intrahepatic portosystemic stent insertion [8,9], but no changes have been reported with antiviral therapy. Cachexia is an important factor determining the prognosis of liver disease, and current treatments are limited to high-energy and high-protein diets, administration of branched-chain amino acids, and so on, the effects of which are also limited [10].…”

Treatment to Improve Nutrition and Functional Capacity Evaluation in Liver Transplant Candidates

“…Complications of cirrhosis including infection, ascites, portal hypertension and hepatic encephalopathy are significantly greater in patients with than those without muscle loss [1, 3, 7, 11]. After liver transplantation, muscle strength improves but muscle mass continues to deteriorate and contributes to the post transplant sarcopenia with obesity characterized by reduced muscle mass, increased fat mass and the development of metabolic syndrome or its components [15, 16, 33]. …”