Sarcopenia in Liver Transplantation
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Purpose of Review
Sarcopenia is highly prevalent in end-stage liver disease (ESLD) patients and has been linked to poor outcomes on the wait list and post-transplantation. This current perspectives article reviews the ongoing challenges to define sarcopenia in ESLD patients, describes associations of sarcopenia with wait list and post-transplantation outcomes, and provides summarized data on efforts to prevent and treat sarcopenia through novel interventions.
Supervised exercise programs improve muscle strength, but muscle mass outcomes are limited by short study follow-up times. Branched-chain amino acid supplementation may ameliorate sarcopenia in ESLD patients, but studies are limited by low participant numbers and confounding. Myostatin inhibition is shown to improve sarcopenia in elderly, frail patients; further study is needed in ESLD patients. Correction of low testosterone improves sarcopenia in male ESLD patients.
Recent literature supports sarcopenia as an independent risk factor for poor outcomes in ESLD patients. Ongoing study is limited by poor standardization of sarcopenia definition and relevant muscle mass cutoffs. Supervised exercise programs should be encouraged for all ESLD patients. More advanced therapies require further clinical investigation before their widespread use.
KeywordsLiver transplantation Sarcopenia Muscle mass Muscle strength Outcomes Exercise Branched-chain amino acids Myostatin Testosterone
Compliance with Ethical Standards
Conflict of Interest
John Montgomery declares no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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- 7.Cramer JT, Cruz-Jentoft AJ, Landi F, Hickson M, Zamboni M, Pereira SL, et al. Impacts of high-protein oral nutritional supplements among malnourished men and women with sarcopenia: a multicenter, randomized, double-blinded, controlled trial. J Am Med Dir Assoc. 2016;17(11):1044–55.CrossRefGoogle Scholar
- 10.van Vugt JL, Levolger S, de Bruin RW, van Rosmalen J, Metselaar HJ, JN IJ. Systematic review and meta-analysis of the impact of computed tomography-assessed skeletal muscle mass on outcome in patients awaiting or undergoing liver transplantation. Am J Transplant. 2016;16(8):2277–92.CrossRefGoogle Scholar
- 14.Hamaguchi Y, Kaido T, Okumura S, Kobayashi A, Shirai H, Yagi S, et al. Impact of skeletal muscle mass index, intramuscular adipose tissue content, and visceral to subcutaneous adipose tissue area ratio on early mortality of living donor liver transplantation. Transplantation. 2017;101(3):565–74.CrossRefGoogle Scholar
- 16.Han A, Bokshan SL, Marcaccio SE, DePasse JM, Daniels AH. Diagnostic criteria and clinical outcomes in sarcopenia research: a literature review. J Clin Med. 2018;7(4).Google Scholar
- 19.Giusto M, Lattanzi B, Albanese C, Galtieri A, Farcomeni A, Giannelli V, et al. Sarcopenia in liver cirrhosis: the role of computed tomography scan for the assessment of muscle mass compared with dual-energy X-ray absorptiometry and anthropometry. Eur J Gastroenterol Hepatol. 2015;27(3):328–34.CrossRefGoogle Scholar
- 20.Wada Y, Kamishima T, Shimamura T, Kawamura N, Yamashita K, Sutherland K, et al. Pre-operative volume rather than area of skeletal muscle is a better predictor for post-operative risks for respiratory complications in living-donor liver transplantation. Br J Radiol. 2017;90(1072):20160938.CrossRefGoogle Scholar
- 27.van Vugt JLA, Alferink LJM, Buettner S, et al. A model including sarcopenia surpasses the MELD score in predicting waiting list mortality in cirrhotic liver transplant candidates: a competing risk analysis in a national cohort. J Hepatol. 2017.Google Scholar
- 53.•• Zenith L, Meena N, Ramadi A, et al. Eight weeks of exercise training increases aerobic capacity and muscle mass and reduces fatigue in patients with cirrhosis. Clin Gastroenterol Hepatol. 2014;12(11):1920–1926.e1922. Improvement of sarcopenia components over relatively short time frame supports inclusion of supervised exercise program into clinical practice. CrossRefGoogle Scholar
- 54.Zenith L, Qamar H, Myers R, et al. Severe muscle mass loss in cirrhosis: can bedside tools be used to predict a CT or MRI diagnosis of sarcopenia. Can J Gastroenterol. 2013;27(Suppl A):83A.Google Scholar
- 61.Toshima T, Shirabe K, Kurihara T, Itoh S, Harimoto N, Ikegami T, et al. Profile of plasma amino acids values as a predictor of sepsis in patients following living donor liver transplantation: special reference to sarcopenia and postoperative early nutrition. Hepatol Res. 2015;45(12):1170–7.CrossRefGoogle Scholar
- 66.•• Uojima H, Sakurai S, Hidaka H, et al. Effect of branched-chain amino acid supplements on muscle strength and muscle mass in patients with liver cirrhosis. Eur J Gastroenterol Hepatol. 2017;29(12):1402–7. Treatment with BCAAs improved muscle strength in ESLD patients when compared with controls. Given low side effect profile, this encourages clinical adoption. However, further US trials with larger number of sarcopenic ESLD patients and longer follow-up are needed. CrossRefGoogle Scholar
- 70.•• Becker C, Lord SR, Studenski SA, et al. Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial. Lancet Diabetes Endocrinol. 2015;3(12):948–57 Novel inhibition of myostatin has shown efficacy in phase II study of elderly, frail, non-cirrhotic patients to decrease sarcopenia. Further studies in ESLD patients are necessary. CrossRefGoogle Scholar
- 74.•• Sinclair M, Grossmann M, Hoermann R, Angus PW, Gow PJ. Testosterone therapy increases muscle mass in men with cirrhosis and low testosterone: a randomised controlled trial. J Hepatol. 2016;65(5):906–913. Treatment of low testosterone in ESLD patients is associated with decreased sarcopenia, but further studies in US population are needed before clinical adoption can be recommended. Google Scholar