Current Transplantation Reports

, Volume 5, Issue 3, pp 199–205 | Cite as

Transplantation for the Very Sick Patient—Donor and Recipient Factors

  • Arjuna Singanayagam
  • William BernalEmail author
Liver Transplantation (D Mulligan, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Liver Transplantation


Purpose of Review

Patients with end-stage chronic liver disease (CLD) frequently deteriorate with development of a ‘frail’ state and progress to development of extra-hepatic organ failures. Making the clinical judgement when a patient is ‘too sick’ to proceed with liver transplantation is challenging; we summarise recent studies that may inform decision-making.

Recent Findings

Reports quantify the impact of both recipient and donor factors related to early post-transplant survival, with consistent adverse association of advanced donor and recipient age, under-nutrition, sarcopenia and impaired functional status, and requirement for critical care unit admission and organ support. Survival for ‘very sick’ recipients has shown progressive improvement over time, but evidence is increasing of much greater post-transplant resource use and cost.


Factors associated with adverse outcomes in very sick recipients are becoming more clearly delineated. The increasing success of transplantation and exploration of its extended use must be tempered by the recognition of the consequences upon constrained clinical resources.


Frailty Performance status Sarcopenia ACLF Outcome prediction 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have 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.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major Importance

  1. 1.
    •• Asrani SK, Saracino G, O'Leary JG, et al. Recipient characteristics and morbidity and mortality after liver transplantation. J Hepatol. 2018;15:15. Large national study identifying key recipient factors predictive of post-transplant morbidity and mortality. Google Scholar
  2. 2.
    •• Bittermann T, Makar G, Goldberg DS. Early post-transplant survival: interaction of MELD score and hospitalization status. J Hepatol. 2015;63(3):601–8. Analysis of UNOS dataset confirming and quantifying impact of hospitalisation on post-transplant outcome. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Wai H, Stepanova M, Saab S, Erario M, Srishord M, Younossi ZM. Inpatient economic and mortality assessment for liver transplantation: a nationwide study of the United States data from 2005 to 2009. Transplantation. 2014;97(1):98–103.CrossRefPubMedGoogle Scholar
  4. 4.
    Keswani RN, Ahmed A, Keeffe EB. Older age and liver transplantation: a review. Liver Transpl. 2004;10(8):957–67.CrossRefPubMedGoogle Scholar
  5. 5.
    • Sonny A, Kelly D, Hammel JP, Albeldawi M, Zein N, Cywinski JB. Predictors of poor outcome among older liver transplant recipients. Clin Transpl. 2015;29(3):197–203. Single centre analysis of predictors of outcome in elderly recipients CrossRefGoogle Scholar
  6. 6.
    Aloia TA, Knight R, Gaber AO, Ghobrial RM, Goss JA. Analysis of liver transplant outcomes for United Network for Organ Sharing recipients 60 years old or older identifies multiple model for end-stage liver disease-independent prognostic factors. Liver Transpl. 2010;16(8):950–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Malinis MF, Chen S, Allore HG, Quagliarello VJ. Outcomes among older adult liver transplantation recipients in the model of end stage liver disease (MELD) era. Ann Transplant. 2014;19:478–87.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Sharpton SR, Feng S, Hameed B, Yao F, Lai JC. Combined effects of recipient age and model for end-stage liver disease score on liver transplantation outcomes. Transplantation. 2014;98(5):557–62.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    VanWagner LB, Lapin B, Skaro AI, Lloyd-Jones DM, Rinella ME. Impact of renal impairment on cardiovascular disease mortality after liver transplantation for nonalcoholic steatohepatitis cirrhosis. Liver Int. 2015;35(12):2575–83.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Skaro AI, Gallon LG, Lyuksemburg V, Jay CL, Zhao L, Ladner DP, et al. The impact of coronary artery disease on outcomes after liver transplantation. J Cardiovasc Med (Hagerstown). 2016;17(12):875–85.CrossRefGoogle Scholar
  11. 11.
    Dick AA, Spitzer AL, Seifert CF, et al. Liver transplantation at the extremes of the body mass index. Liver Transpl. 2009;15(8):968–77.CrossRefPubMedGoogle Scholar
  12. 12.
    Volk ML, Hernandez JC, Lok AS, Marrero JA. Modified Charlson comorbidity index for predicting survival after liver transplantation. Liver Transpl. 2007;13(11):1515–20.CrossRefPubMedGoogle Scholar
  13. 13.
    Cywinski JB, Alster JM, Miller C, Vogt DP, Parker BM. Prediction of intraoperative transfusion requirements during orthotopic liver transplantation and the influence on postoperative patient survival. Anesth Analg. 2014;118(2):428–37.CrossRefPubMedGoogle Scholar
  14. 14.
    Kalafateli M, Mantzoukis K, Choi Yau Y, Mohammad AO, Arora S, Rodrigues S, et al. Malnutrition and sarcopenia predict post-liver transplantation outcomes independently of the Model for End-stage Liver Disease score. J Cachexia Sarcopenia Muscle. 2017;8(1):113–21.CrossRefPubMedGoogle Scholar
  15. 15.
    •• 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. Prospective study documenting functional deterioration of patients on transplant waitlist and association with increased risk of death, independent of MELD score CrossRefPubMedGoogle Scholar
  16. 16.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Serper M, Bittermann T, Rossi M, et al. Functional status, healthcare utilization, and the costs of liver transplantation. Am J Transplant. 2017;08:08.Google Scholar
  18. 18.
    • Dasarathy S, Merli M. Sarcopenia from mechanism to diagnosis and treatment in liver disease. J Hepatol. 2016;65(6):1232–44. Comprehensive review of mechanisms and consequences of sarcopenia in chronic liver disease CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Tapper EB, Su GL. Does Karnofsky performance status of patients with cirrhosis on the transplant waitlist meet the eyeball test? Clin Gastroenterol Hepatol. 2016;14(8):1196–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Jacob M, Copley LP, Lewsey JD, Gimson A, Rela M, van der Meulen J, et al. Functional status of patients before liver transplantation as a predictor of posttransplant mortality. Transplantation. 2005;80(1):52–7.CrossRefPubMedGoogle Scholar
  21. 21.
    •• Dolgin NH, Martins PN, Movahedi B, Lapane KL, Anderson FA, Bozorgzadeh A. Functional status predicts postoperative mortality after liver transplantation. Clin Transpl. 2016;30(11):1403–10. Large national study assessing impact of pre-transplant functional status on predictive of post-transplant mortality CrossRefGoogle Scholar
  22. 22.
    Orman ES, Ghabril M, Chalasani N. Poor performance status is associated with increased mortality in patients with cirrhosis. Clin Gastroenterol Hepatol. 2016;14(8):1189–1195.e1.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Lai JC, Volk ML, Strasburg D, Alexander N. Performance-based measures associate with frailty in patients with end-stage liver disease. Transplantation. 2016;100(12):2656–60.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    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.CrossRefPubMedGoogle Scholar
  25. 25.
    Montano-Loza AJ, Meza-Junco J, Baracos VE, Prado CMM, Ma M, Meeberg G, et al. Severe muscle depletion predicts postoperative length of stay but is not associated with survival after liver transplantation. Liver Transpl. 2014;20(6):640–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Valero V 3rd, Amini N, Spolverato G, et al. Sarcopenia adversely impacts postoperative complications following resection or transplantation in patients with primary liver tumors. J Gastrointest Surg. 2015;19(2):272–81.CrossRefPubMedGoogle Scholar
  27. 27.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Yadav A, Chang YH, Carpenter S, Silva AC, Rakela J, Aqel BA, et al. Relationship between sarcopenia, six-minute walk distance and health-related quality of life in liver transplant candidates. Clin Transpl. 2015;29(2):134–41.CrossRefGoogle Scholar
  29. 29.
    Wynter-Blyth V, Moorthy K. Prehabilitation: preparing patients for surgery. BMJ. 2017;358:j3702.CrossRefPubMedGoogle Scholar
  30. 30.
    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):1920–1926.e2.CrossRefPubMedGoogle Scholar
  31. 31.
    Roman E, Garcia-Galceran C, Torrades T, 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.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    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.CrossRefPubMedGoogle Scholar
  33. 33.
    Jacob M, Copley LP, Lewsey JD, Gimson A, Toogood GJ, Rela M, et al. Pretransplant MELD score and post liver transplantation survival in the UK and Ireland. Liver Transpl. 2004;10(7):903–7.CrossRefPubMedGoogle Scholar
  34. 34.
    Foxton MR, Al-Freah MA, Portal AJ, et al. Increased model for end-stage liver disease score at the time of liver transplant results in prolonged hospitalization and overall intensive care unit costs. Liver Transpl. 2010;16(5):668–77.PubMedGoogle Scholar
  35. 35.
    Alexopoulos S, Matsuoka L, Cho Y, Thomas E, Sheikh M, Stapfer M, et al. Outcomes after liver transplantation in patients achieving a model for end-stage liver disease score of 40 or higher. Transplantation. 2013;95(3):507–12.CrossRefPubMedGoogle Scholar
  36. 36.
    Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013;144(7):1426–37. 37.e1–9CrossRefPubMedGoogle Scholar
  37. 37.
    Karvellas CJ, Lescot T, Goldberg P, et al. Liver transplantation in the critically ill: a multicenter Canadian retrospective cohort study. Crit Care (London England). 2013;17(1):R28.CrossRefGoogle Scholar
  38. 38.
    Levesque E, Winter A, Noorah Z, Daurès JP, Landais P, Feray C, et al. Impact of acute-on-chronic liver failure on 90-day mortality following a first liver transplantation. Liver Int. 2017;37(5):684–93.CrossRefPubMedGoogle Scholar
  39. 39.
    • Putignano A, Gustot T. New concepts in acute-on-chronic liver failure: implications for liver transplantation. Liver Transpl. 2017;23(2):234–43. Review of current status of transplantation of patients with ACLF. CrossRefPubMedGoogle Scholar
  40. 40.
    Huebener P, Sterneck MR, Bangert K, et al. Stabilisation of acute-on-chronic liver failure patients before liver transplantation predicts post-transplant survival. Aliment Pharmacol Ther. 2018;02:02.Google Scholar
  41. 41.
    Montenovo MI, Hansen RN, Dick AAS, Reyes J. Donor age still matters in liver transplant: results from the united network for organ sharing-scientific registry of transplant recipients database. Exp Clin Transplant. 2017;15(5):536–41.PubMedGoogle Scholar
  42. 42.
    Amin MG, Wolf MP, JA TB Jr, et al. Expanded criteria donor grafts for deceased donor liver transplantation under the MELD system: a decision analysis. [see comment]. Liver Transpl. 2004;10:1468–75. 2004 DecCrossRefPubMedGoogle Scholar
  43. 43.
    Merion RM, Schaubel DE, Dykstra DM, Freeman RB, Port FK, Wolfe RA. The survival benefit of liver transplantation. Am J Transplant. 2005;5(2):307–13.CrossRefPubMedGoogle Scholar
  44. 44.
    Maluf DG, Edwards EB, Kauffman HM. Utilization of extended donor criteria liver allograft: is the elevated risk of failure independent of the model for end-stage liver disease score of the recipient? Transplantation. 2006;82(12):1653–7.CrossRefPubMedGoogle Scholar
  45. 45.
    Bonney GK, Aldersley MA, Asthana S, Toogood GJ, Pollard SG, Lodge JPA, et al. Donor risk index and MELD interactions in predicting long-term graft survival: a single-centre experience. Transplantation. 2009;87(12):1858–63.CrossRefPubMedGoogle Scholar
  46. 46.
    Grat M, Wronka KM, Patkowski W, et al. Effects of donor age and cold ischemia on liver transplantation outcomes according to the severity of recipient status. Dig Dis Sci. 2016;61(2):626–35.CrossRefPubMedGoogle Scholar
  47. 47.
    Doyle MB, Vachharajani N, Wellen JR, Anderson CD, Lowell JA, Shenoy S, et al. Short- and long-term outcomes after steatotic liver transplantation. Arch Surg. 2010;145(7):653–60.CrossRefPubMedGoogle Scholar
  48. 48.
    Spitzer AL, Lao OB, Dick AA, et al. The biopsied donor liver: incorporating macrosteatosis into high-risk donor assessment. Liver Transpl. 2010;16(7):874–84.CrossRefPubMedGoogle Scholar
  49. 49.
    Westerkamp AC, de Boer MT, van den Berg AP, Gouw AS, Porte RJ. Similar outcome after transplantation of moderate macrovesicular steatotic and nonsteatotic livers when the cold ischemia time is kept very short. Transpl Int. 2015;28(3):319–29.CrossRefPubMedGoogle Scholar
  50. 50.
    Schlegel A, Linecker M, Kron P, Györi G, de Oliveira ML, Müllhaupt B, et al. Risk assessment in high- and low-MELD liver transplantation. Am J Transplant. 2017;17(4):1050–63.CrossRefPubMedGoogle Scholar
  51. 51.
    Bernal W. Improving outcomes for transplantation of critically ill patients with cirrhosis? Clinical Liver Disease. 2017;10(1):25–8.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Kings College HospitalInstitute of Liver StudiesLondonUK

Personalised recommendations