Patients with Alcoholic Liver Disease Have Worse Functional Status at Time of Liver Transplant Registration and Greater Waitlist and Post-transplant Mortality Which Is Compounded by Older Age

  • Patrick McCabe
  • Artin Galoosian
  • Robert J. WongEmail author
Original Article



Worse functional status correlates with increased mortality on the liver transplant (LT) waitlist. Whether functional status affects LT outcomes equally across cirrhosis etiologies is unclear.


We evaluate the impact of functional status on waitlist and post-LT mortality stratified by etiology and age.


Functional status among US adults from 2005 to 2017 United Network for Organ Sharing LT registry data was retrospectively evaluated using Karnofsky Performance Status Score (KPS-1 = functional status 80–100%, KPS-2 = 60–70%, KPS-3 = 40–50%, KPS-4 = 10–30%). Waitlist and post-LT survival were stratified by KPS and cirrhosis etiology, including alcoholic liver disease (ALD), nonalcoholic steatohepatitis (NASH), hepatitis C (HCV), and HCV/ALD, and evaluated using Kaplan–Meier and multivariate Cox proportional hazard models.


Among 94,201 waitlist registrants (69.4% men, 39.5% HCV, 26.7% ALD, 23.2% NASH), ALD patients had worse functional status compared to HCV (KPS-4: 17.2% vs. 8.3%, p < 0.001). Worse functional status at time of waitlist registration was associated with higher 90-day waitlist mortality with the greatest effect in ALD (KPS-4 vs. KPS-1: ALD HR 2.16, 95% CI 1.83–2.55; HCV HR 2.17, 95% CI 1.87–2.51). Similar trends occurred in 5-year post-LT survival with ALD patients the most harmed. Compared to patients < 50 years, patients ≥ 65 years had increased waitlist mortality at 90-days if they had HCV or HCV/ALD, and 5-year post-LT mortality regardless of cirrhosis etiology with ALD patients most severely affected.


In a retrospective cohort study of patients, US ALD patients had disparately worse functional status at time of LT waitlist registration. Worse functional status correlated with higher risk of waitlist and post-LT mortality, affecting ALD and HCV patients the most.


MELD UNOS/OPTN Cirrhosis Mortality Karnofsky Frailty Liver transplantation 



Alcoholic liver disease


Eastern Cooperative Oncology Group


Hepatocellular carcinoma


Hepatitis C virus


Karnofsky Performance Status


Liver transplantation


Model for end-stage liver disease


Organ Procurement and Transplant Network


United Network for Organ Sharing


Compliance with Ethical Standards

Conflict of interest



  1. 1.
    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;63:574–580.CrossRefGoogle Scholar
  2. 2.
    McCabe P, Wong RJ. More severe deficits in functional status associated with higher mortality among adults awaiting liver transplantation. Clin Transplant. 2018;32:e13346.CrossRefGoogle Scholar
  3. 3.
    Orman ES, Ghabril M, Chalasani N. Poor performance status is associated with increased mortality in patients with cirrhosis. Clin Gastroenterol Hepatol. 2016;14(8):1189.e1–1195.e1.CrossRefGoogle Scholar
  4. 4.
    Samoylova ML, Covinsky KE, Haftek M, Kuo S, Roberts JP, Lai JC. Disability in patients with end-stage liver disease: results from the functional assessment in liver transplantation study. Liver Transpl. 2017;23:292–298.CrossRefGoogle Scholar
  5. 5.
    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.CrossRefGoogle Scholar
  6. 6.
    Wang CW, Lebsack A, Chau S, Lai JC. The range and reproducibility of the liver frailty index. Liver Transpl. 2019;25:841–847.CrossRefGoogle Scholar
  7. 7.
    Karnofsky DA, Burchenal J. The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod CM, ed. evaluation of chemotherapeutic agents. New York: Columbia University Press; 1949.Google Scholar
  8. 8.
    Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649–655.CrossRefGoogle Scholar
  9. 9.
    Wong RJ, Aguilar M, Cheung R, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148:547–555.CrossRefGoogle Scholar
  10. 10.
    Wong RJ, Cheung R, Ahmed A. Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the US. Hepatology. 2014;59:2188–2195.CrossRefGoogle Scholar
  11. 11.
    Thuluvath PJ, Thuluvath AJ, Savva Y. Karnofsky performance status before and after liver transplantation predicts graft and patient survival. J Hepatol. 2018;69:818–825.CrossRefGoogle Scholar
  12. 12.
    Malinis MF, Chen S, Allore HG, Quagliarello VJ, et al. Outcomes among older adult liver transplantation recipients in the model of end stage liver disease (MELD) era. Ann Transplant. 2014;19:478–487.CrossRefGoogle Scholar
  13. 13.
    McCabe P, Gish RG, Cheung R, Wong RJ. More severe deficits in performance status at time of liver transplant is associated with significantly higher risk of death following liver transplantation. J Clin Gastroenterol. 2019;53:e392–e399.CrossRefGoogle Scholar
  14. 14.
    Thuluvath PJ, Hanish S, Savva Y. Waiting list mortality and transplant rates for NASH cirrhosis when compared with cryptogenic, alcoholic, or AIH cirrhosis. Transplantation. 2019;103:113–121.CrossRefGoogle Scholar
  15. 15.
    Goldberg D, French B, Abt P, Feng S, Cameron AM. Increasing disparity in waitlist mortality rates with increased model for end-stage liver disease scores for candidates with hepatocellular carcinoma versus candidates without hepatocellular carcinoma. Liver Transpl. 2012;18:434–443.CrossRefGoogle Scholar
  16. 16.
    Trivedi HD, Tapper EB. Interventions to improve physical function and prevent adverse events in cirrhosis. Gastroenterology Report. 2018;6:13–20.CrossRefGoogle Scholar
  17. 17.
    Lucey MR. Liver transplantation in patients with alcoholic liver disease. Liver Transpl. 2011;17:751–759.CrossRefGoogle Scholar
  18. 18.
    Adachi J, Asano M, Ueno Y, et al. Alcoholic muscle disease and biomembrane perturbations (review). J Nutr Biochem. 2003;14:616–625.CrossRefGoogle Scholar
  19. 19.
    Sacanella E, Fernández-Solà J, Cofan M, et al. Chronic alcoholic myopathy: diagnostic clues and relationship with other ethanol-related diseases. QJM. 1995;88:811–817.PubMedGoogle Scholar
  20. 20.
    Marroni CA, Fleck AM, Fernandes SA, et al. Liver transplantation and alcoholic liver disease: history, controversies, and considerations. World J Gastroenterol. 2018;24:2785–2805.CrossRefGoogle Scholar
  21. 21.
    Grat M, Lewandowski Z, Grąt K, et al. Negative outcomes after liver transplantation in patients with alcoholic liver disease beyond the fifth post-transplant year. Clin Transplant. 2014;28:1112–1120.CrossRefGoogle Scholar
  22. 22.
    Galant LH, Forgiarini Junior LA, Dias AS, Marroni CA. Functional status, respiratory muscle strength, and quality of life in patients with cirrhosis. Brazilian Journal of Physical Therapy. 2012;16:30–34.CrossRefGoogle Scholar
  23. 23.
    Bryce CL, Angus DC, Arnold RM, et al. Sociodemographic differences in early access to liver transplantation services. Am J Transplant. 2009;9:2092–2101.CrossRefGoogle Scholar
  24. 24.
    Shah ND, Cots MV, Zhang C, Zahiragic N. Worldwide lack of early referral of patients with alcoholic liver disease: results of the global alcoholic liver disease survey (GLADIS). J Hepatology. 2017;66:S107–S108.CrossRefGoogle Scholar
  25. 25.
    Ursic-Bedoya J, Faure S, Donnadieu-Rigole H, Pageaux GP. Liver transplantation for alcoholic liver disease: lessons learned and unresolved issues. World J Gastroenterol. 2015;21:10994–11002.CrossRefGoogle Scholar
  26. 26.
    dos Santos DC, Limongi V, Oliveira da Silva AM, et al. Evaluation of functional status, pulmonary capacity, body composition, and quality of life of end-stage liver disease patients who are candidates for liver surgery. Transplant Proc. 2014;46:1771–1774.CrossRefGoogle Scholar
  27. 27.
    Duarte-Rojo A, et al. 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;24:122–139.CrossRefGoogle Scholar
  28. 28.
    Mizuno Y, et al. Changes in muscle strength and six-minute walk distance before and after living donor liver transplantation. Transplant Proc. 2016;48:3348–3355.CrossRefGoogle Scholar
  29. 29.
    Ow MM, et al. Impaired functional capacity in potential liver transplant candidates predicts short-term mortality before transplantation. Liver Transpl. 2014;20:1081–1088.CrossRefGoogle Scholar
  30. 30.
    Prentis JM, et al. Submaximal cardiopulmonary exercise testing predicts 90-day survival after liver transplantation. Liver Transpl. 2012;18:152–159.CrossRefGoogle Scholar
  31. 31.
    Tandon P, Ney M, Irwin I, Ma M, et al. Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value. Liver Transpl. 2012;18:1209–1216.CrossRefGoogle Scholar
  32. 32.
    Wang CW, Feng S, Covinsky KE, 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;100:1692–1698.CrossRefGoogle Scholar
  33. 33.
    Bolondi G, Mocchegiani F, Montalti R, Nicolini D, Vivarelli M, De Pietri L. Predictive factors of short term outcome after liver transplantation: a review. World J Gastroenterol. 2016;22:5936–5949.CrossRefGoogle Scholar
  34. 34.
    Schag CC, Heinrich RL, Ganz PA. Karnofsky performance status revisited: reliability, validity, and guidelines. J Clin Oncol. 1984;2:187–193.CrossRefGoogle Scholar
  35. 35.
    Mor V, Laliberte L, Morris JN, Wiemann M. The Karnofsky performance status scale. An examination of its reliability and validity in a research setting. Cancer. 1984;53:2002–2007.CrossRefGoogle Scholar
  36. 36.
    Dunn MA, Josbeno DA, Schmotzer AR, et al. The gap between clinically assessed physical performance and objective physical activity in liver transplant candidates. Liver Transpl. 2016;22:1324–1332.CrossRefGoogle Scholar
  37. 37.
    Wang CW, Lai JC. Reporting functional status in UNOS: the weakness of the Karnofsky performance status scale. Clin Transpl 2017. 31.CrossRefGoogle Scholar
  38. 38.
    Lai JC, Covinsky KE, McCulloch CE, Feng S. The liver frailty index improves mortality prediction of the subjective clinician assessment in patients with cirrhosis. Am J Gastroenterol. 2018;113:235–242.CrossRefGoogle Scholar
  39. 39.
    Lai JC, Covinsky KE, Hayssen H, et al. Author response to: clinical assessments of health status as a potential marker to identify patients who are too sick to undergo transplantation. Liver Int. 2016;36:611.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Gastroenterology and Hepatology, Department of MedicineCalifornia Pacific Medical CenterSan FranciscoUSA
  2. 2.Department of MedicineCalifornia Pacific Medical CenterSan FranciscoUSA
  3. 3.Division of Gastroenterology and HepatologyAlameda Health System – Highland HospitalOaklandUSA

Personalised recommendations