Review Article

Tale of the Frail: Understanding Frailty in Cirrhosis

Authors: Faruq Pradhan, MD, Natasha Narang, DO, Michael Fallon, MD


Abstract: Frailty is a dynamic condition that results in increased vulnerability to health stressors. Often associated with older adults, frailty is not limited to the geriatric population, although aging and disease burden often go hand in hand. This syndrome is recognized increasingly as an important factor in healthcare costs, rate of adverse outcomes, and overall resource utilization. Frailty may be reversible to a degree, and thus appropriate recognition affords a focus for efficient intervention. Notably, frailty is becoming increasingly relevant in cirrhosis, and has been noted to be an independent predictor of outcomes in patients both before and after liver transplantation. Cirrhosis is currently the 12th leading cause of death in the United States, and its incidence is anticipated to markedly increase in the coming years with the aging of our population. With the anticipated surge in disease prevalence, liver disease care will likely shift from specialist-driven to a multidisciplinary approach between primary care physicians, internists, and hepatologists to adequately care for these patients. This review serves as a guide for clinicians to learn about frailty, its role in cirrhosis, and the current tools to educate patients and families about the importance of nutrition and physical exercise within this population.

Posted in: Liver Disease3

This content is limited to qualifying members.

Existing members, please login first.

If you have an existing account please login now to access this article or view your purchase options.

Purchase only this article ($15)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.


1. Brown RT, Covinsky KE. Frailty as an outcome in geriatrics research: not ready for prime time? Ann Intern Med 2018;168:361–362.
2. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol 2001;56:M146–M157.
3. 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;19:1896–1906.
4. Ney M, Tangri N, Dobbs B, et al. Predicting hepatic encephalopathy-related hospitalizations using a composite assessment of cognitive impairment and frailty in 355 patients with cirrhosis. Am J Gastroenterol 2018;113:1–10.
5. European Association for the Study of the Liver. EASL Clinical Practice  Guidelines on nutrition in chronic liver disease. J Hepatol 2019;70:172–193.
6. Meza-Junco J, Montano-Loza AJ, Baracos VE, et al. Sarcopenia as a prognostic index of nutritional status in concurrent cirrhosis and hepatocellular carcinoma. J Clin Gastroenterol 2013;47:861–870.
7. Biswas A, Oh PI, Faulkner GE, et al. Sedentary time and its association with risk for disease incidence, mortality, and hospitalization in adults: a systematic review and meta-analysis. Ann Intern Med 2015;162:123–132.
8. Montano-Loza AJ, Meza-Junco J, Prado CM, et al. Muscle wasting is associated with mortality in patients with cirrhosis. Clin Gastroenterol Hepatol 2012;10:166–173.
9. Dasarathy S. Myostatin and beyond in cirrhosis: all roads lead to sarcopenia. J Cachexia Sarcopenia Muscle 2017;8:864–869.
10. 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;31:165–174.
11. Villareal DT, Banks M, Sinacore DR, et al. Effect of weight loss and exercise on frailty in obese older adults. Arch Intern Med 2006;166:860–866.
12. Montano-Loza AJ, Angulo P, Meza-Junco J, et al. Sarcopenic obesity and myosteatosis are associated with higher mortality in patients with cirrhosis. J Cachexia Sarcopenia Muscle 2016;7:126–135.
13. Jang HC. Sarcopenia, frailty, and diabetes in older adults. Diabetes Metab J 2016;40:182–189.
14. Lai JC, Feng S, Terrault NA, et al. Frailty predicts waitlist mortality in liver transplant candidates. Am J Transplant 2014;14:1870–1879.
15. Rockwood K, Song X, MacKnight C, et al. A global clinical measure of fitness and frailty in elderly people. CMAJ 2005;173:489–495.
16. Tandon P, Tangri N, Thomas L, et al. A rapid bedside screen to predict unplanned hospitalization and death in outpatients with cirrhosis: a prospective evaluation of the clinical frailty scale. Am J Gastroenterol 2016;111:1759–1767.
17. Tapper EB, Finkelstein D, Mittleman MA, Piatkowski G, Lai M. Standard assessments of frailty are validated predictors of mortality in hospitalized patients with cirrhosis. Hepatology 2015;62:584–590.
18. Samoylova ML, Covinsky KE, Haftek M, et al. Disability in patients with end-stage liver disease: results from the functional assessment in liver transplantation study. Liver Transpl 2017;23:292–298.
19. 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;66:564–574.
20. Prado CM, Lieffers JR, McCargar LJ, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 2008;9:629–635.
21. Shen W, Punyanitya M, Wang Z, et al. Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross-sectional image. J Appl Physiol 2004;97:2333–2338.
22. Carey EJ, Lai JC, Wang CW, et al. A multicenter study to define sarcopenia in patients with end-stage liver disease. Liver Transpl 2017;23:625–633.
23. Amodio P, Bemeur C, Butterworth R, et al. The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus. Hepatology 2013;58:325–336.
24. Arora S, Mattina C, McAnenny C, et al. The development and validation of a nutritional prioritising tool for use in patients with chronic liver disease. J Hepatol 2012;56:S241.
25. Booi AN, Menendez J, Norton HJ, et al. Validation of a screening tool to identify undernutrition in ambulatory patients with liver cirrhosis. Nutr Clin Pract 2015;30:683–689.
26. Crow RS, Lohman MC, Titus AJ, et al. Association of obesity and frailty in older adults: NHANES 1999–2004. J Nutr Health Aging 2019;23:138–144.
27. Landré B, Czernichow S, Goldberg M, et al. Association between life-course obesity and frailty in older adults: findings in the GAZEL cohort. Obesity 2020;28:388–396.
28. Lai JC, Segev DL, McCulloch CE, et al. Physical frailty after liver transplantation. Am J Transplant 2018;18:1986–1994.
29. Grossmann M, Hoermann R, Gani L, et al. Low testosterone levels as an independent predictor of mortality in men with chronic liver disease. Clin Endocrinol 2012;77:323–328.
30. Sinclair M, Grossmann M, Hoermann R, et al. Testosterone therapy increases muscle mass in men with cirrhosis and low testosterone: a randomised controlled trial. J Hepatol 2016;65:906–913.
31. Sinclair M, Grossmann M, Gow PJ, et al. Testosterone in men with advanced liver disease: abnormalities and implications. J Gastroenterol Hepatol 2015;30:244–251.
32. Jahangiri Y, Pathak P, Tomozawa Y, et al. Muscle gain after transjugular intrahepatic portosystemic shunt creation: time course and prognostic implications for survival in cirrhosis. J Vasc Interv Radiol 2019;30:866–872.
33. Tandon P, Ismond KP, Riess K, et al. Exercise in cirrhosis: translating evidence and experience to practice. J Hepatol 2018;69:1164–1177.
34. Cirrhosis Care Clinic, University of Alberta. Nutrition in cirrhosis guide. Published 2017. Accessed January 11, 2021.
35. Beste LA, Harp BK, Blais RK, et al. Primary care providers report challenges to cirrhosis management and specialty care coordination. Dig Dis Sci 2005;60:2628–2635.