Skip to main content
Top
Published in: Digestive Diseases and Sciences 2/2016

Open Access 01-02-2016 | Original Article

Effects of Donor Age and Cold Ischemia on Liver Transplantation Outcomes According to the Severity of Recipient Status

Authors: Michał Grąt, Karolina M. Wronka, Waldemar Patkowski, Jan Stypułkowski, Karolina Grąt, Maciej Krasnodębski, Łukasz Masior, Zbigniew Lewandowski, Marek Krawczyk

Published in: Digestive Diseases and Sciences | Issue 2/2016

Login to get access

Abstract

Background

Prolonged cold ischemic time (CIT) and increased donor age are well-known factors negatively influencing outcomes after liver transplantation (LT).

Aims

The aim of this study was to evaluate whether the magnitude of their negative effects is related to recipient model for end-stage liver disease (MELD) score.

Methods

This retrospective study was based on a cohort of 1402 LTs, divided into those performed in low-MELD (<10), moderate-MELD (10–20), and high-MELD (>20) recipients.

Results

While neither donor age (p = 0.775) nor CIT (p = 0.561) was a significant risk factor for worse 5-year graft survival in low-MELD recipients, both were found to yield independent effects (p = 0.003 and p = 0.012, respectively) in moderate-MELD recipients, and only CIT (p = 0.004) in high-MELD recipients. However, increased donor age only triggered the negative effect of CIT in moderate-MELD recipients, which was limited to grafts recovered from donors aged ≥46 years (p = 0.019). Notably, utilization of grafts from donors aged ≥46 years with CIT ≥9 h in moderate-MELD recipients (p = 0.003) and those with CIT ≥9 h irrespective of donor age in high-MELD recipients (p = 0.031) was associated with particularly compromised outcomes.

Conclusions

In conclusion, the negative effects of prolonged CIT seem to be limited to patients with moderate MELD receiving organs procured from older donors and to high-MELD recipients, irrespective of donor age. Varying effects of donor age and CIT according to recipient MELD score should be considered during the allocation process in order to avoid high-risk matches.
Literature
1.
go back to reference Dutkowski P, Linecker M, DeOliveira ML, Müllhaupt B, Clavien PA. Challenges to liver transplantation and strategies to improve outcomes. Gastroenterology. 2015;148:307–323.CrossRefPubMed Dutkowski P, Linecker M, DeOliveira ML, Müllhaupt B, Clavien PA. Challenges to liver transplantation and strategies to improve outcomes. Gastroenterology. 2015;148:307–323.CrossRefPubMed
2.
go back to reference Kim WR, Lake JR, Smith JM, et al. OPTN/SRTR 2013 annual data report: liver. Am J Transpl. 2015;15:1–28.CrossRef Kim WR, Lake JR, Smith JM, et al. OPTN/SRTR 2013 annual data report: liver. Am J Transpl. 2015;15:1–28.CrossRef
3.
go back to reference Johnson RJ, Bradbury LL, Martin K, Neuberger J, UK Transplant Registry. Organ donation and transplantation in the UK-the last decade: a report from the UK national transplant registry. Transplantation. 2014;97:S1–S27.CrossRefPubMed Johnson RJ, Bradbury LL, Martin K, Neuberger J, UK Transplant Registry. Organ donation and transplantation in the UK-the last decade: a report from the UK national transplant registry. Transplantation. 2014;97:S1–S27.CrossRefPubMed
4.
go back to reference Klein AS, Messersmith EE, Ratner LE, Kochik R, Baliga PK, Ojo AO. Organ donation and utilization in the United States, 1999–2008. Am J Transpl. 2010;10:973–986.CrossRef Klein AS, Messersmith EE, Ratner LE, Kochik R, Baliga PK, Ojo AO. Organ donation and utilization in the United States, 1999–2008. Am J Transpl. 2010;10:973–986.CrossRef
5.
go back to reference Chu KK, Chan SC, Sharr WW, Chok KS, Dai WC, Lo CM. Low-volume deceased donor liver transplantation alongside a strong living donor liver transplantation service. World J Surg. 2014;38:1522–1528.CrossRefPubMed Chu KK, Chan SC, Sharr WW, Chok KS, Dai WC, Lo CM. Low-volume deceased donor liver transplantation alongside a strong living donor liver transplantation service. World J Surg. 2014;38:1522–1528.CrossRefPubMed
6.
go back to reference Wan P, Li Q, Zhang J, Xia Q. Right lobe split liver transplantation versus whole liver transplantation in adult recipients: a systematic review and meta-analysis. Liver Transpl. 2015. doi:10.1002/lt.24135.PubMed Wan P, Li Q, Zhang J, Xia Q. Right lobe split liver transplantation versus whole liver transplantation in adult recipients: a systematic review and meta-analysis. Liver Transpl. 2015. doi:10.​1002/​lt.​24135.PubMed
7.
go back to reference Müllhaupt B, Dimitroulis D, Gerlach JT, Clavien PA. Hot topics in liver transplantation: organ allocation-extended criteria donor–living donor liver transplantation. J Hepatol. 2008;48:S58–67.CrossRefPubMed Müllhaupt B, Dimitroulis D, Gerlach JT, Clavien PA. Hot topics in liver transplantation: organ allocation-extended criteria donor–living donor liver transplantation. J Hepatol. 2008;48:S58–67.CrossRefPubMed
8.
go back to reference Silberhumer GR, Rahmel A, Karam V, et al. The difficulty in defining extended donor criteria for liver grafts: the Eurotransplant experience. Transpl Int. 2013;26:990–998.CrossRefPubMed Silberhumer GR, Rahmel A, Karam V, et al. The difficulty in defining extended donor criteria for liver grafts: the Eurotransplant experience. Transpl Int. 2013;26:990–998.CrossRefPubMed
9.
go back to reference Feng S, Goodrich NP, Bragg-Gresham JL, et al. Characteristics associated with liver graft failure: the concept of a donor risk index. Am J Transpl. 2006;6:783–790.CrossRef Feng S, Goodrich NP, Bragg-Gresham JL, et al. Characteristics associated with liver graft failure: the concept of a donor risk index. Am J Transpl. 2006;6:783–790.CrossRef
10.
go back to reference Braat AE, Blok JJ, Putter H, et al. The Eurotransplant donor risk index in liver transplantation: ET-DRI. Am J Transpl. 2012;12:2789–2796.CrossRef Braat AE, Blok JJ, Putter H, et al. The Eurotransplant donor risk index in liver transplantation: ET-DRI. Am J Transpl. 2012;12:2789–2796.CrossRef
11.
go back to reference Cameron AM, Ghobrial RM, Yersiz H, et al. Optimal utilization of donor grafts with extended criteria: a single-center experience in over 1000 liver transplants. Ann Surg. 2006;243:748–753.PubMedCentralCrossRefPubMed Cameron AM, Ghobrial RM, Yersiz H, et al. Optimal utilization of donor grafts with extended criteria: a single-center experience in over 1000 liver transplants. Ann Surg. 2006;243:748–753.PubMedCentralCrossRefPubMed
12.
go back to reference Bloom MB, Raza S, Bhakta A, et al. Impact of deceased organ donor demographics and critical care end points on liver transplantation and graft survival rates. J Am Coll Surg. 2015;220:38–47.CrossRefPubMed Bloom MB, Raza S, Bhakta A, et al. Impact of deceased organ donor demographics and critical care end points on liver transplantation and graft survival rates. J Am Coll Surg. 2015;220:38–47.CrossRefPubMed
13.
go back to reference Subramanian V, Seetharam AB, Vachharajani N, et al. Donor graft steatosis influences immunity to hepatitis C virus and allograft outcome after liver transplantation. Transplantation. 2011;92:1259–1268.PubMedCentralCrossRefPubMed Subramanian V, Seetharam AB, Vachharajani N, et al. Donor graft steatosis influences immunity to hepatitis C virus and allograft outcome after liver transplantation. Transplantation. 2011;92:1259–1268.PubMedCentralCrossRefPubMed
14.
go back to reference Mangus RS, Fridell JA, Vianna RM, et al. Severe hypernatremia in deceased liver donors does not impact early transplant outcome. Transplantation. 2010;90:438–443.CrossRefPubMed Mangus RS, Fridell JA, Vianna RM, et al. Severe hypernatremia in deceased liver donors does not impact early transplant outcome. Transplantation. 2010;90:438–443.CrossRefPubMed
15.
go back to reference Stahl JE, Kreke JE, Malek FA, Schaefer AJ, Vacanti J. Consequences of cold-ischemia time on primary nonfunction and patient and graft survival in liver transplantation: a meta-analysis. PLoS One. 2008;3:e2468.PubMedCentralCrossRefPubMed Stahl JE, Kreke JE, Malek FA, Schaefer AJ, Vacanti J. Consequences of cold-ischemia time on primary nonfunction and patient and graft survival in liver transplantation: a meta-analysis. PLoS One. 2008;3:e2468.PubMedCentralCrossRefPubMed
16.
go back to reference Cassuto JR, Patel SA, Tsoulfas G, Orloff MS, Abt PL. The cumulative effects of cold ischemic time and older donor age on liver graft survival. J Surg Res. 2008;148:38–44.CrossRefPubMed Cassuto JR, Patel SA, Tsoulfas G, Orloff MS, Abt PL. The cumulative effects of cold ischemic time and older donor age on liver graft survival. J Surg Res. 2008;148:38–44.CrossRefPubMed
17.
go back to reference Agopian VG, Petrowsky H, Kaldas FM, et al. The evolution of liver transplantation during 3 decades: analysis of 5347 consecutive liver transplants at a single center. Ann Surg. 2013;258:409–421.CrossRefPubMed Agopian VG, Petrowsky H, Kaldas FM, et al. The evolution of liver transplantation during 3 decades: analysis of 5347 consecutive liver transplants at a single center. Ann Surg. 2013;258:409–421.CrossRefPubMed
18.
go back to reference Burroughs AK, Sabin CA, Rolles K, et al. 3- and 12-month mortality after first liver transplant in adults in Europe: predictive models for outcome. Lancet. 2006;367:225–232.CrossRefPubMed Burroughs AK, Sabin CA, Rolles K, et al. 3- and 12-month mortality after first liver transplant in adults in Europe: predictive models for outcome. Lancet. 2006;367:225–232.CrossRefPubMed
19.
go back to reference Kim WR, Biggins SW, Kremers WK, et al. Hyponatremia and mortality among patients on the liver-transplant waiting list. N Engl J Med. 2008;359:1018–1026.PubMedCentralCrossRefPubMed Kim WR, Biggins SW, Kremers WK, et al. Hyponatremia and mortality among patients on the liver-transplant waiting list. N Engl J Med. 2008;359:1018–1026.PubMedCentralCrossRefPubMed
20.
go back to reference Halldorson JB, Bakthavatsalam R, Fix O, Reyes JD, Perkins JD. D-MELD, a simple predictor of post liver transplant mortality for optimization of donor/recipient matching. Am J Transpl. 2009;9:318–326.CrossRef Halldorson JB, Bakthavatsalam R, Fix O, Reyes JD, Perkins JD. D-MELD, a simple predictor of post liver transplant mortality for optimization of donor/recipient matching. Am J Transpl. 2009;9:318–326.CrossRef
21.
go back to reference Dutkowski P, Oberkofler CE, Slankamenac K, et al. Are there better guidelines for allocation in liver transplantation? A novel score targeting justice and utility in the model for end-stage liver disease era. Ann Surg. 2011;254:745–753.CrossRefPubMed Dutkowski P, Oberkofler CE, Slankamenac K, et al. Are there better guidelines for allocation in liver transplantation? A novel score targeting justice and utility in the model for end-stage liver disease era. Ann Surg. 2011;254:745–753.CrossRefPubMed
22.
go back to reference Rana A, Hardy MA, Halazun KJ, et al. Survival outcomes following liver transplantation (SOFT) score: a novel method to predict patient survival following liver transplantation. Am J Transpl. 2008;8:2537–2546.CrossRef Rana A, Hardy MA, Halazun KJ, et al. Survival outcomes following liver transplantation (SOFT) score: a novel method to predict patient survival following liver transplantation. Am J Transpl. 2008;8:2537–2546.CrossRef
23.
go back to reference Angelico M, Nardi A, Romagnoli R, et al. A Bayesian methodology to improve prediction of early graft loss after liver transplantation derived from the liver match study. Dig Liver Dis. 2014;46:340–347.CrossRefPubMed Angelico M, Nardi A, Romagnoli R, et al. A Bayesian methodology to improve prediction of early graft loss after liver transplantation derived from the liver match study. Dig Liver Dis. 2014;46:340–347.CrossRefPubMed
24.
go back to reference Stey AM, Doucette J, Florman S, Emre S. Donor and recipient factors predicting time to graft failure following orthotopic liver transplantation: a transplant risk index. Transpl Proc. 2013;45:2077–2082.CrossRef Stey AM, Doucette J, Florman S, Emre S. Donor and recipient factors predicting time to graft failure following orthotopic liver transplantation: a transplant risk index. Transpl Proc. 2013;45:2077–2082.CrossRef
25.
go back to reference Krawczyk M, Grąt M, Barski K, et al. 1000 liver transplantations at the Department of General, Transplant and Liver Surgery, Medical University of Warsaw—analysis of indications and results. Pol Przegl Chir. 2012;84:304–312.PubMed Krawczyk M, Grąt M, Barski K, et al. 1000 liver transplantations at the Department of General, Transplant and Liver Surgery, Medical University of Warsaw—analysis of indications and results. Pol Przegl Chir. 2012;84:304–312.PubMed
26.
go back to reference Marti J, Fuster J, Navasa M, et al. Effects of graft quality on non-urgent liver retransplantation survival: Should we avoid high-risk donors? World J Surg. 2012;36:2914–2922.CrossRefPubMed Marti J, Fuster J, Navasa M, et al. Effects of graft quality on non-urgent liver retransplantation survival: Should we avoid high-risk donors? World J Surg. 2012;36:2914–2922.CrossRefPubMed
27.
go back to reference Routh D, Sharma S, Naidu CS, Rao PP, Sharma AK, Ranjan P. Comparison of outcomes in ideal donor and extended criteria donor in deceased donor liver transplant: a prospective study. Int J Surg. 2014;12:774–777.CrossRefPubMed Routh D, Sharma S, Naidu CS, Rao PP, Sharma AK, Ranjan P. Comparison of outcomes in ideal donor and extended criteria donor in deceased donor liver transplant: a prospective study. Int J Surg. 2014;12:774–777.CrossRefPubMed
28.
go back to reference Callaghan CJ, Charman SC, Muiesan P, et al. Outcomes of transplantation of livers from donation after circulatory death donors in the UK: a cohort study. BMJ Open. 2013;3:e003287.PubMedCentralCrossRefPubMed Callaghan CJ, Charman SC, Muiesan P, et al. Outcomes of transplantation of livers from donation after circulatory death donors in the UK: a cohort study. BMJ Open. 2013;3:e003287.PubMedCentralCrossRefPubMed
29.
go back to reference de Graaf EL, Kench J, Dilworth P, et al. Grade of deceased donor liver macrovesicular steatosis impacts graft and recipient outcomes more than the Donor Risk Index. J Gastroenterol Hepatol. 2012;27:540–546.CrossRefPubMed de Graaf EL, Kench J, Dilworth P, et al. Grade of deceased donor liver macrovesicular steatosis impacts graft and recipient outcomes more than the Donor Risk Index. J Gastroenterol Hepatol. 2012;27:540–546.CrossRefPubMed
30.
31.
go back to reference Tekin K, Imber CJ, Atli M, et al. A simple scoring system to evaluate the effects of cold ischemia on marginal liver donors. Transplantation. 2004;77:411–416.CrossRefPubMed Tekin K, Imber CJ, Atli M, et al. A simple scoring system to evaluate the effects of cold ischemia on marginal liver donors. Transplantation. 2004;77:411–416.CrossRefPubMed
32.
go back to reference Schlegel A, Dutkowski P. Role of hypothermic machine perfusion in liver transplantation. Transpl Int. 2015;28:677–689.CrossRefPubMed Schlegel A, Dutkowski P. Role of hypothermic machine perfusion in liver transplantation. Transpl Int. 2015;28:677–689.CrossRefPubMed
33.
go back to reference Oniscu GC, Randle LV, Muiesan P, et al. In situ normothermic regional perfusion for controlled donation after circulatory death–the United Kingdom experience. Am J Transplant. 2014;14:2846–2854.CrossRefPubMed Oniscu GC, Randle LV, Muiesan P, et al. In situ normothermic regional perfusion for controlled donation after circulatory death–the United Kingdom experience. Am J Transplant. 2014;14:2846–2854.CrossRefPubMed
34.
go back to reference Guarrera JV, Henry SD, Samstein B, et al. Hypothermic machine preservation facilitates successful transplantation of “orphan” extended criteria donor livers. Am J Transplant. 2015;15:161–169.CrossRefPubMed Guarrera JV, Henry SD, Samstein B, et al. Hypothermic machine preservation facilitates successful transplantation of “orphan” extended criteria donor livers. Am J Transplant. 2015;15:161–169.CrossRefPubMed
35.
go back to reference Fontes P, Lopez R, van der Plaats A, et al. Liver preservation with machine perfusion and a newly developed cell-free oxygen carrier solution under subnormothermic conditions. Am J Transplant. 2015;15:381–394.CrossRefPubMed Fontes P, Lopez R, van der Plaats A, et al. Liver preservation with machine perfusion and a newly developed cell-free oxygen carrier solution under subnormothermic conditions. Am J Transplant. 2015;15:381–394.CrossRefPubMed
36.
go back to reference Bruinsma BG, Yeh H, Ozer S, et al. Subnormothermic machine perfusion for ex vivo preservation and recovery of the human liver for transplantation. Am J Transplant. 2014;14:1400–1409.PubMedCentralCrossRefPubMed Bruinsma BG, Yeh H, Ozer S, et al. Subnormothermic machine perfusion for ex vivo preservation and recovery of the human liver for transplantation. Am J Transplant. 2014;14:1400–1409.PubMedCentralCrossRefPubMed
37.
go back to reference Adam R, Delvart V, Karam V, et al. Compared efficacy of preservation solutions in liver transplantation: a long-term graft outcome study from the European Liver Transplant Registry. Am J Transplant. 2015;15:395–406.CrossRefPubMed Adam R, Delvart V, Karam V, et al. Compared efficacy of preservation solutions in liver transplantation: a long-term graft outcome study from the European Liver Transplant Registry. Am J Transplant. 2015;15:395–406.CrossRefPubMed
38.
go back to reference Wong RJ, Chou C, Bonham CA, Concepcion W, Esquivel CO, Ahmed A. Improved survival outcomes in patients with nonalcoholic steatohepatitis and alcoholic liver disease following liver transplantation: an analysis of 2002-2012 United Network for Organ Sharing data. Clin Transplant. 2014;28:713–721.CrossRefPubMed Wong RJ, Chou C, Bonham CA, Concepcion W, Esquivel CO, Ahmed A. Improved survival outcomes in patients with nonalcoholic steatohepatitis and alcoholic liver disease following liver transplantation: an analysis of 2002-2012 United Network for Organ Sharing data. Clin Transplant. 2014;28:713–721.CrossRefPubMed
39.
go back to reference Nagai S, Yoshida A, Facciuto M, et al. Ischemia time impacts recurrence of hepatocellular carcinoma after liver transplantation. Hepatology. 2015;61:895–904.CrossRefPubMed Nagai S, Yoshida A, Facciuto M, et al. Ischemia time impacts recurrence of hepatocellular carcinoma after liver transplantation. Hepatology. 2015;61:895–904.CrossRefPubMed
40.
go back to reference Salgia RJ, Goodrich NP, Marrero JA, Volk ML. Donor factors similarly impact survival outcome after liver transplantation in hepatocellular carcinoma and non-hepatocellular carcinoma patients. Dig Dis Sci. 2014;59:214–219.CrossRefPubMed Salgia RJ, Goodrich NP, Marrero JA, Volk ML. Donor factors similarly impact survival outcome after liver transplantation in hepatocellular carcinoma and non-hepatocellular carcinoma patients. Dig Dis Sci. 2014;59:214–219.CrossRefPubMed
41.
go back to reference Bonney GK, Aldersley MA, Asthana S, et al. Donor risk index and MELD interactions in predicting long-term graft survival: a single-centre experience. Transplantation. 2009;87:1858–1863.CrossRefPubMed Bonney GK, Aldersley MA, Asthana S, et al. Donor risk index and MELD interactions in predicting long-term graft survival: a single-centre experience. Transplantation. 2009;87:1858–1863.CrossRefPubMed
42.
go back to reference Schaubel DE, Sima CS, Goodrich NP, Feng S, Merion RM. The survival benefit of deceased donor liver transplantation as a function of candidate disease severity and donor quality. Am J Transplant. 2008;8:419–425.CrossRefPubMed Schaubel DE, Sima CS, Goodrich NP, Feng S, Merion RM. The survival benefit of deceased donor liver transplantation as a function of candidate disease severity and donor quality. Am J Transplant. 2008;8:419–425.CrossRefPubMed
Metadata
Title
Effects of Donor Age and Cold Ischemia on Liver Transplantation Outcomes According to the Severity of Recipient Status
Authors
Michał Grąt
Karolina M. Wronka
Waldemar Patkowski
Jan Stypułkowski
Karolina Grąt
Maciej Krasnodębski
Łukasz Masior
Zbigniew Lewandowski
Marek Krawczyk
Publication date
01-02-2016
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 2/2016
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-015-3910-7

Other articles of this Issue 2/2016

Digestive Diseases and Sciences 2/2016 Go to the issue
Obesity Clinical Trial Summary

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.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

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

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

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

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