Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Treatment Options in Gastroenterology
Published in: Current Treatment Options in Gastroenterology 2/2018

01-06-2018 | Liver (J Bajaj, Section Editor)

Frailty in Patients With Cirrhosis

Authors: Beverley Kok, MBBS, Puneeta Tandon, MD

Published in: Current Treatment Options in Gastroenterology | Issue 2/2018

Login to get access

Abstract

Purpose of review

This review gives an overview of the evolving concept of physical frailty in patients with cirrhosis. As well as summarizing the available metrics that have been used to diagnose it, this review also examines the major recent trials that have investigated frailty in patients with cirrhosis. The complex relationship between sarcopenia and frailty is explored, and strategies to optimize frailty, such as including pharmacological and non-pharmacological therapies, are discussed.

Recent findings

Though there is heterogeneity between studies on how physical frailty in cirrhosis has been assessed, it is nonetheless becoming increasingly apparent that frailty in cirrhosis contributes to poor outcomes. A growing body of evidence strongly supports that frailty, as an entity distinct from comorbidity or measurable by laboratory-based liver disease severity, contributes to pre-transplant mortality and unplanned hospital admissions. If taken into account, frailty may improve pre-transplant mortality risk prediction.

Summary

Physical frailty in cirrhosis may be objectively assessed by a number of validated metrics though at present, we lack a uniform consensus on the most appropriate tool. Early identification of frailty may allow optimization of the patient with the potential to avoiding adverse outcomes. Further studies are awaited validating and exploring optimal approaches to diagnosing and reversing frailty.
Literature
1.
Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–56.PubMedCrossRef
2.
Angulo J, El Assar M, Rodriguez-Manas L. Frailty and sarcopenia as the basis for the phenotypic manifestation of chronic diseases in older adults. Mol Asp Med. 2016;50:1–32.CrossRef
3.
Lai JC, Covinsky KE, Hayssen H, Lizaola B, Dodge JL, Roberts JP, et al. Clinician assessments of health status predict mortality in patients with end-stage liver disease awaiting liver transplantation. Liver Int. 2015;35(9):2167–73.PubMedPubMedCentralCrossRef
4.
•• Lai JC, Feng S, Terrault NA, Lizaola B, Hayssen H, Covinsky K. Frailty predicts waitlist mortality in liver transplant candidates. Am J Transplant. 2014;14(8):1870–9. Landmark study introducing the concept of frailty and its negative impact on outcomes in patients with cirrhosis.PubMedPubMedCentralCrossRef
5.
• Tandon P, Tangri N, Thomas L, Zenith L, Shaikh T, Carbonneau M, 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(12):1759–67. Study supporting the use of a “clinic-friendly” global frailty scale to rapidly screen patients and identify whether they were at high risk of unplanned hospitalization or death.PubMedCrossRef
6.
• Dunn MA, Josbeno DA, Tevar AD, Rachakonda V, Ganesh SR, Schmotzer AR, 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):1768–75. Study supporting the use of a single component assessment—gait speed—as a marker of hospitalization in patients with cirrhosis. Relevant discussion about the cost implications of frailty.PubMedCrossRef
7.
•• Lai JC, Covinsky KE, Dodge JL, Boscardin WJ, Segev DL, Roberts JP, et al. Development of a novel frailty index to predict mortality in patients with end-stage liver disease. Hepatology. 2017;66(2):564–74. This study provides clinicians with a prospectively established battery of 3 tools—the “liver frailty index” for the prediction of waitlist mortality.PubMedCrossRef
8.
Bruyere O, Buckinx F, Beaudart C, Reginster JY, Bauer J, Cederholm T, et al. How clinical practitioners assess frailty in their daily practice: an international survey. Aging Clin Exp Res. 2017;29(5):905–12.PubMedPubMedCentralCrossRef
9.
• Carey EJ, Steidley DE, Aqel BA, Byrne TJ, Mekeel KL, Rakela J, et al. Six-minute walk distance predicts mortality in liver transplant candidates. Liver Transpl. 2010;16(12):1373–8. A seminal study which highlighted the impact of muscle function on outcomes in patients with cirrhosis.PubMedCrossRef
10.
Roberts RE, Vernon SW. The Center for Epidemiologic Studies Depression Scale: its use in a community sample. Am J Psychiatry. 1983;140(1):41–6.PubMedCrossRef
11.
Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, et al. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005;173(5):489–95.PubMedPubMedCentralCrossRef
12.
Mitnitski AB, Mogilner AJ, MacKnight C, Rockwood K. The mortality rate as a function of accumulated deficits in a frailty index. Mech Ageing Dev. 2002;123(11):1457–60.PubMedCrossRef
13.
Teng EL, Chui HC. The Modified Mini-Mental State (3MS) examination. J Clin Psychiatry. 1987;48(8):314–8.PubMed
14.
Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, et al. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994;49(2):M85–94.PubMedCrossRef
15.
Volpato S, Cavalieri M, Sioulis F, Guerra G, Maraldi C, Zuliani G, et al. Predictive value of the Short Physical Performance Battery following hospitalization in older patients. J Gerontol A Biol Sci Med Sci. 2011;66((1):89–96.CrossRef
16.
ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002;166(1):111–7.
17.
Lai JC, Dodge JL, Sen S, Covinsky K, Feng S. Functional decline in patients with cirrhosis awaiting liver transplantation: results from the functional assessment in liver transplantation (FrAILT) study. Hepatology. 2016;63(2):574–80.PubMedCrossRef
18.
Sinclair M, Poltavskiy E, Dodge JL, Lai JC. Frailty is independently associated with increased hospitalisation days in patients on the liver transplant waitlist. World J Gastroenterol. 2017;23(5):899–905.PubMedPubMedCentralCrossRef
19.
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(2):584–90.PubMedPubMedCentralCrossRef
20.
Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW. Studies of illness in the aged. The index of ADL: a standardized measure of biological and psychosocial function. JAMA. 1963;185:914–9.PubMedCrossRef
21.
Bergstrom N, Braden B, Kemp M, Champagne M, Ruby E. Predicting pressure ulcer risk: a multisite study of the predictive validity of the Braden Scale. Nurs Res. 1998;47(5):261–9.PubMedCrossRef
22.
Morse JM, Tylko SJ, Dixon HA. The patient who falls—and falls again: defining the aged at risk. J Gerontol Nurs. 1985;11(11):15–8.PubMedCrossRef
23.
Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010;39(4):412–23.PubMedPubMedCentralCrossRef
24.
25.
26.
Carey EJ, Lai JC, Wang CW, Dasarathy S, Lobach I, Montano-Loza AJ, et al. A multicenter study to define sarcopenia in patients with end-stage liver disease. Liver Transpl. 2017;23(5):625–33.PubMedPubMedCentralCrossRef
27.
Cederholm T, Barazzoni R, Austin P, Ballmer P, Biolo G, Bischoff SC, et al. ESPEN guidelines on definitions and terminology of clinical nutrition. Clin Nutr. 2017;36(1):49–64.PubMedCrossRef
28.
Landi F, Calvani R, Cesari M, Tosato M, Martone AM, Bernabei R, et al. Sarcopenia as the biological substrate of physical frailty. Clin Geriatr Med. 2015;31(3):367–74.PubMedCrossRef
29.
Kim G, Kang SH, Kim MY, Baik SK. Prognostic value of sarcopenia in patients with liver cirrhosis: a systematic review and meta-analysis. PLoS One. 2017;12(10):e0186990.PubMedPubMedCentralCrossRef
30.
van Vugt JL, Levolger S, de Bruin RW, van Rosmalen J, Metselaar HJ, Systematic Review JNIJ. Meta-analysis of the impact of computed tomography-assessed skeletal muscle mass on outcome in patients awaiting or undergoing liver transplantation. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2016;16(8):2277–92.CrossRef
31.
Merli M, Giusto M, Lucidi C, Giannelli V, Pentassuglio I, Di Gregorio V, et al. Muscle depletion increases the risk of overt and minimal hepatic encephalopathy: results of a prospective study. Metab Brain Dis. 2013;28(2):281–4.PubMedCrossRef
32.
Nardelli S, Lattanzi B, Torrisi S, Greco F, Farcomeni A, Gioia S, et al. Sarcopenia is risk factor for development of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt placement. Clin Gastroenterol Hepatol. 2017;15(6):934–6.PubMedCrossRef
33.
Goodpaster BH, Park SW, Harris TB, Kritchevsky SB, Nevitt M, Schwartz AV, et al. The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study. J Gerontol A Biol Sci Med Sci. 2006;61(10):1059–64.PubMedCrossRef
34.
Tandon P, Low G, Mourtzakis M, Zenith L, Myers RP, Abraldes JG, et al. A model to identify sarcopenia in patients with cirrhosis. Clin Gastroenterol Hepatol. 2016;14(10):1473–80.e3.PubMedCrossRef
35.
Wang CW, Feng S, Covinsky KE, Hayssen H, Zhou LQ, Yeh BM, et al. A comparison of muscle function, mass, and quality in liver transplant candidates: results from the functional assessment in liver transplantation study. Transplantation. 2016;100(8):1692–8.PubMedPubMedCentralCrossRef
36.
Tsien C, Shah SN, McCullough AJ, Dasarathy S. Reversal of sarcopenia predicts survival after a transjugular intrahepatic portosystemic stent. Eur J Gastroenterol Hepatol. 2013;25(1):85–93.PubMedCrossRef
37.
Hirsch S, Bunout D, de la Maza P, Iturriaga H, Petermann M, Icazar G, et al. Controlled trial on nutrition supplementation in outpatients with symptomatic alcoholic cirrhosis. JPEN J Parenter Enteral Nutr. 1993;17(2):119–24.PubMedCrossRef
38.
Marchesini G, Bianchi G, Merli M, Amodio P, Panella C, Loguercio C, et al. Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology. 2003;124(7):1792–801.PubMedCrossRef
39.
Ney M, Vandermeer B, van Zanten SJ, Ma MM, Gramlich L, Tandon P. Meta-analysis: oral or enteral nutritional supplementation in cirrhosis. Aliment Pharmacol Ther. 2013;37(7):672–9.PubMedCrossRef
40.
41.
Plauth M, Cabre E, Riggio O, Assis-Camilo M, Pirlich M, Kondrup J, et al. ESPEN guidelines on enteral nutrition: liver disease. Clin Nutr. 2006;25(2):285–94.PubMedCrossRef
42.
Amodio P, Bemeur C, Butterworth R, Cordoba J, Kato A, Montagnese S, et al. The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus. Hepatology. 2013;58(1):325–36.PubMedCrossRef
43.
Tsien CD, McCullough AJ, Dasarathy S. Late evening snack: exploiting a period of anabolic opportunity in cirrhosis. J Gastroenterol Hepatol. 2012;27(3):430–41.PubMedCrossRef
44.
• Plank LD, Gane EJ, Peng S, Muthu C, Mathur S, Gillanders L, et al. Nocturnal nutritional supplementation improves total body protein status of patients with liver cirrhosis: a randomized 12-month trial. Hepatology. 2008;48(2):557–66. Key study illuminating the beneficial effect on lean body mass in patients with cirrhosis by avoiding prolonged overnight fasting.PubMedCrossRef
45.
Duarte-Rojo A, Ruiz-Margain A, Montano-Loza AJ, Macias-Rodriguez RU, Ferrando A, Kim WR. Exercise and physical activity for patients with end-stage liver disease: improving functional status and sarcopenia while on the transplant waiting list. Liver Transpl. 2018;24(1):122–39.PubMedCrossRef
46.
Zenith L, Meena N, Ramadi A, Yavari M, Harvey A, Carbonneau M, 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):1920–6.e2.PubMedCrossRef
47.
Fiatarone MA, O’Neill EF, Ryan ND, Clements KM, Solares GR, Nelson ME, et al. Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med. 1994;330(25):1769–75.PubMedCrossRef
48.
Garcia-Pagan JC, Santos C, Barbera JA, Luca A, Roca J, Rodriguez-Roisin R, et al. Physical exercise increases portal pressure in patients with cirrhosis and portal hypertension. Gastroenterology. 1996;111(5):1300–6.PubMedCrossRef
49.
Debette-Gratien M, Tabouret T, Antonini MT, Dalmay F, Carrier P, Legros R, et al. Personalized adapted physical activity before liver transplantation: acceptability and results. Transplantation. 2015;99(1):145–50.PubMedCrossRef
50.
Roman E, Garcia-Galceran C, Torrades T, Herrera S, Marin A, Donate M, et al. Effects of an exercise programme on functional capacity, body composition and risk of falls in patients with cirrhosis: a randomized clinical trial. PLoS One. 2016;11(3):e0151652.PubMedPubMedCentralCrossRef
51.
Neff GW, O'Brien CB, Montalbano M, Meyer D, DeManno A, Muslu H, et al. Beneficial effects of topical testosterone replacement in patients with end-stage liver disease. Dig Dis Sci. 2004;49(7–8):1186–9.PubMedCrossRef
52.
Neff GW, O'Brien CB, Shire NJ, DeManno A, Kahn S, Rideman E, et al. Topical testosterone treatment for chronic allograft failure in liver transplant recipients with recurrent hepatitis C virus. Transplant Proc. 2004;36(10):3071–4.PubMedCrossRef
53.
Yurci A, Yucesoy M, Unluhizarci K, Torun E, Gursoy S, Baskol M, et al. Effects of testosterone gel treatment in hypogonadal men with liver cirrhosis. Clin Res Hepatol Gastroenterol. 2011;35(12):845–54.PubMedCrossRef
54.
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):906–13.PubMedCrossRef
Metadata
Title
Frailty in Patients With Cirrhosis
Authors
Beverley Kok, MBBS
Puneeta Tandon, MD
Publication date
01-06-2018
Publisher
Springer US
Published in
Current Treatment Options in Gastroenterology / Issue 2/2018
Print ISSN: 1092-8472
Electronic ISSN: 1534-309X
DOI
https://doi.org/10.1007/s11938-018-0179-x

Other articles of this Issue 2/2018

Current Treatment Options in Gastroenterology 2/2018 Go to the issue

Liver (J Bajaj, Section Editor)

Interaction Between Hepatocellular Carcinoma and Hepatitis C Eradication With Direct-acting Antiviral Therapy

Liver (J Bajaj, Section Editor)

Intensive Care Management of Patients with Cirrhosis

Liver (J Bajaj, Section Editor)

Management of Hepatic Encephalopathy Not Responsive to First-Line Treatments

Esophagus (P Iyer, Section Editor)

Esophageal Stenting in Clinical Practice: an Overview

Liver (J Bajaj, Section Editor)

The Use of Statins in Patients With Chronic Liver Disease and Cirrhosis
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits