Sarcopenia, myosteatosis and frailty in patients with liver cirrhosis

Czech version

Authors: D. Erhartová Kyselová ^1,2; Irena Míková ¹; Pavel Trunečka ¹
Authors‘ workplace: Klinika hepatogastroenterologie, IKEM, Praha 2 Fyziologický ústav 1. LF UK, Praha ¹
Published in: Gastroent Hepatol 2022; 76(4): 288-295
Category: Clinical and Experimental Gastroenterology: Review Article
doi: https://doi.org/10.48095/ccgh2022288

Overview

Skeletal muscles are the biggest tissue in healthy people (30–40% of total body mass) and they comprise three quarters of total body proteins. Muscle alterations, especially muscle wasting and loss of muscle function, have an indisputable prognostic value in the outcome of chronic diseases, including chronic liver diseases. Muscle wasting is associated with higher morbidity, mortality and poor quality of life. The terms sarcopenia and myosteatosis are used to describe specific muscle alterations, both forming substantial components of multidimensional construct “frailty syndrome”. Sarcopenia is defined as loss of muscle mass and/or loss of muscle function. It is usually diagnosed using the skeletal muscle index from computed tomography (CT) image analysis at the L3 vertebra. Myosteatosis is defined as an excess intramyocelullar and intermyocellular fat deposition. Diagnosis of myosteatosis is based on a measurement of skeletal muscle density by CT imaging at the L3 vertebra (skeletal muscle radiation attenuation – SM-RA). Besides muscle alterations and decreased physical performance, frailty syndrome also comprises changes of other organ systems, leading to the loss of functional reserves and higher vulnerability. Different scoring systems, such as Fried Frailty Index (FFI) or modified Liver Frailty Index (LFI) for patients with liver cirrhosis, are used to diagnose patients with frail phenotype. The principle of the treatment of patients with muscle alterations is therapy of liver disease (including liver transplant in advanced cirrhosis), improvement of the nutritional status, adequate physical activity and supplementation of vitamin D deficiency, if necessary. In this review, we summarize up-to-date knowledge about pathophysiology, diagnostic tools and treatment options of sarcopenia, myosteatosis and frailty syndrome in patients with liver cirrhosis

Keywords:

sarcopenia – liver cirrhosis – myosteatosis – frailty syndrome

Sources

1. Nachit M, Leclercq IA. Emerging awareness on the importance of skeletal muscle in liver diseases: Time to dig deeper into mechanisms! Clin Sci (Lond) 2019; 133 (3): 465-481. doi: 10.1042/CS20180421.

2. Kazemi-Bajestani SMR, Mazurak VC, Baracos V. Computed tomography-defined muscle and fat wasting are associated with cancer clinical outcomes. Semin Cell Dev Biol 2016; 54: 2–10. doi: 10.1016/j.semcdb.2015.09.001.

3. Kroenke CH, Prado CM, Meyerhardt JA et al. Muscle radiodensity and mortality in patients with colorectal cancer. Cancer 2018; 124 (14): 3008–3015. doi: 10.1002/cncr.31405.

4. Tandon P, Montano-Loza AJ, Lai JC et al. Sarcopenia and frailty in decompensated cirrhosis. J Hepatol 2021; 75 (Suppl 1): S147–S162. doi: 10.1016/j.jhep.2021.01.025.

5. Merli M, Riggio O, Dally L. Does malnutrition affect survival in cirrhosis? PINC (Policentrica Italiana Nutrizione Cirrosi). Hepatology 1996; 23 (5): 1041–1046. doi: 10.1002/hep.510230516.

6. Merli M, Berzigotti A, Zelber-Sagi S et al. EASL Clinical Practice Guidelines on nutrition in chronic liver disease. J Hepatol 2019; 70 (1): 172–193. doi: 10.1016/j.jhep.2018.06.024.

7. Bischoff SC, Bernal W, Dasarathy S et al. ESPEN practical guideline: Clinical nutrition in liver disease. Clin Nutr 2020; 39 (12): 3533–3562. doi: 10.1016/j.clnu.2020.09.001.

8. Tantai X, Liu Y, Yeo YH et al. Effect of sarcopenia on survival in patients with cirrhosis: A meta-analysis. J Hepatol 2022; 76 (3): 588–599. doi: 10.1016/j.jhep.2021.11.006.

9. Dasarathy J, McCullough AJ, Dasarathy S. Sarcopenia in Alcoholic Liver Disease: Clinical and Molecular Advances. Alcohol Clin Exp Res 2017; 41 (8): 1419–1431. doi: 10.1111/acer.13425.

10. DiCecco SR, Wieners EJ, Wiesner RH et al. Assessment of Nutritional Status of Patients With End-Stage Liver Disease Undergoing Liver Transplantation. Mayo Clin Proc 1989; 64 (1): 95–102. doi: 10.1016/s0025-6196 (12) 65308-7.

11. Eslamparast T, Montano-Loza AJ, Raman M et al. Sarcopenic obesity in cirrhosis – The confluence of 2 prognostic titans. Liver Int 2018; 38 (10): 1706–1717. doi: 10.1111/liv.13876.

12. van Vugt JLA, Levolger S, de Bruin RWF et al. 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): 2277–2292. doi: 10.1111/ajt.13732.

13. Ebadi M, Tandon P, Moctezuma-Velazquez C et al. Low subcutaneous adiposity associates with higher mortality in female patients with cirrhosis. J Hepatol 2018; 69 (3): 608–616. doi: 10.1016/j.jhep.2018.04.015.

14. Kuo SZ, Ahmad M, Dunn MA et al. Sarcopenia Predicts Post-transplant Mortality in Acutely Ill Men Undergoing Urgent Evaluation and Liver Transplantation. Transplantation 2019; 103 (11): 2312–2317. doi: 10.1097/TP.0000000000002741.

15. Bhanji RA, Moctezuma-Velazquez C, Duarte-Rojo A et al. Myosteatosis and sarcopenia are associated with hepatic encephalopathy in patients with cirrhosis. Hepatol Int 2018; 12 (4): 377–386. doi: 10.1007/s12072-018-9875-9.

16. van Vugt JLA, Buettner S, Alferink LJM et al. Low skeletal muscle mass is associated with increased hospital costs in patients with cirrhosis listed for liver transplantation – a retrospective study. Transpl Int 2018; 31 (2): 165–174. doi: 10.1111/tri.13048.

17. Periyalwar P, Dasarathy S. Malnutrition in Cirrhosis: Contribution and Consequences of Sarcopenia on Metabolic and Clinical Responses. Clin Liver Dis 2012; 16 (1): 95–131. doi: 10.1016/ j.cld.2011.12.009.

18. Bhanji RA, Montano-Loza AJ, Watt KD. Sarcopenia in Cirrhosis: Looking Beyond the Skeletal Muscle Loss to See the Systemic Disease. Hepatology 2019; 70 (6): 2193–2203. doi: 10.1002/hep.30686.

19. van Dijk DPJ, Bakers FCH, Sanduleanu S et al. Myosteatosis predicts survival after surgery for periampullary cancer: a novel method using MRI. HPB (Oxford) 2018; 20 (8): 715–720. doi: 10.1016/j.hpb.2018.02.378.

20. Czigany Z, Kramp W, Bednarsch J et al. Myosteatosis to predict inferior perioperative outcome in patients undergoing orthotopic liver transplantation. Am J Transplant 2020; 20 (2): 493–503. doi: 10.1111/ajt.15577.

21. Míková I, Kyselová D, Kautznerová D et al. Význam sarkopenie a myosteatózy u kandidátů transplantace jater na peritransplantační průběh a přežívání pacientů a štěpů. Gastroent Hepatol 2021; 75 (4): 311–322. doi: 10.48095/ ccgh2021311.

22. Bhanji RA, Narayanan P, Moynagh MR et al. Differing Impact of Sarcopenia and Frailty in Nonalcoholic Steatohepatitis and Alcoholic Liver Disease. Liver Transplant 2019; 25 (1): 14–24. doi: 10.1002/lt.25346.

23. Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev 2018; 98 (4): 2133–2223. doi: 10.1152/ physrev.00063.2017.

24. Van Jacobs AC. Frailty Assessment in Patients with Liver Cirrhosis. Clin Liver Dis (Hoboken) 2019; 14 (3): 121–125. doi: 10.1002/cld.825.

25. Laube R, Wang H, Park L et al. Frailty in advanced liver disease. Liver Int 2018; 38 (12): 2117–2128. doi: 10.1111/liv.13917.

26. Lai JC, Feng S, Terrault NA et al. Frailty predicts waitlist mortality in liver transplant candidates. Am J Transplant 2014; 14 (8): 1870–1879. doi: 10.1111/ajt.12762.

27. Carey EJ, Lai JC, Wang CW, et al. A multicenter study to define sarcopenia in patients with end-stage liver disease. Liver Transplant 2017; 23 (5): 625–633. doi: 10.1002/lt.24750.

28. Carey EJ, Lai JC, Sonnenday C et al. A North American Expert Opinion Statement on Sarcopenia in Liver Transplantation. Hepatology 2019; 70 (5): 1816–1829. doi: 10.1002/hep.30828.

29. Tandon P, Mourtzakis M, Low G et al. Comparing the Variability Between Measurements for Sarcopenia Using Magnetic Resonance Imaging and Computed Tomography Imaging. Am J Transplant 2016; 16 (9): 2766–2767. doi: 10.1111/ajt.13832.

30. Fried LP, Tangen CM, Walston J et al. Frailty in older adults: Evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001; 56 (3): M146–M156. doi: 10.1093/gerona/56.3.m146.

31. Lai JC, Covinsky KE, Dodge JL et al. Development of a novel frailty index to predict mortality in patients with end-stage liver disease. Hepatology 2017; 66 (2): 564–574. doi: 10.1002/hep.29219.

32. Lai JC, Sonnenday CJ, Tapper EB et al. Frailty in liver transplantation: An expert opinion statement from the American Society of Transplantation Liver and Intestinal Community of Practice. Am J Transplant 2019; 19 (7): 1896–1906. doi: 10.1111/ajt.15392.

33. Lin FP, Visina JM, Bloomer PM et al. Prehabilitation-Driven Changes in Frailty Metrics Predict Mortality in Patients With Advanced Liver Disease. Am J Gastroenterol 2021; 116 (10): 2105–2117. doi: 10.14309/ajg.0000000000001376.

34. Tandon P, Ismond KP, Riess K et al. Exercise in cirrhosis: Translating evidence and experience to practice. J Hepatol 2018; 69 (5). 1164–1177. doi: 10.1016/j.jhep.2018.06.017.

35. Dunn MA, Josbeno DA, Tevar AD et al. Frailty as Tested by Gait Speed is an Independent Risk Factor for Cirrhosis Complications that Require Hospitalization. Am J Gastroenterol 2016; 111 (12): 1768–1775. doi: 10.1038/ajg.2016.336.

36. Corey RL, Whitaker MD, Crowell MD et al. Vitamin D deficiency, parathyroid hormone levels, and bone disease among patients with end-stage liver disease and normal serum creatinine awaiting liver transplantation. Clin Transplant 2014; 28 (5): 579–584. doi: 10.1111/ctr.12351.

37. Uchitomi R, Oyabu M, Kamei Y. Vitamin D and sarcopenia: Potential of vitamin D supplementation in sarcopenia prevention and treatment. Nutrients 2020; 12 (10): 3189. doi: 10.3390/nu12103189.

38. Nagasue N, Yukaya H, Chang YC et al. Active uptake of testosterone by androgen receptors of hepatocellular carcinoma in humans. Cancer 1986; 57 (11): 2162–2167. doi: 10.1002/1097-0142 (19860601) 57: 11<2162:: aid-cncr2820571114>3.0.co; 2-6.