The use of expanded criteria donors is one of the strategies used to overcome the gap between the demand for organs and the number of donors. Physicians debate the extent to which marginal grafts can be used. In recent years, normothermic machine perfusion (NMP) has been used to test liver viability before transplantation. Grafts underwent NMP whenever histological steatosis was > 40% or there were at least three Eurotransplant criteria for expanded criteria donor (ECD). We used NMP to test 19 grafts, 3 from donation after type 3 controlled cardiac death (DCD), and 16 from donation after brain death (DBD). Only two grafts from DBD were not transplanted, because perfusion proved they were not suitable (total of 17 transplanted grafts of 19 tested grafts). Kaplan–Meier survival estimates at 30, 90, 180, and 1 year after transplant were all 94% (95% CI 84–100%); estimated 3-years survival was 82% (95% CI 62–100%). Overall survival rates did not differ from those of patients transplanted with non-perfused grafts from an ECD. In our experience, the use of very marginal grafts preventively tested by NMP does not negatively influence the patient’s outcome, and increases the number of transplants in low donation areas.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Availability of data and materials
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Adam R, Karam V, Cailliez V, Grady JGO, Mirza D, Cherqui D, Klempnauer J, Salizzoni M, Pratschke J, Jamieson N et al (2018) Annual report of the European Liver Transplant Registry (ELTR)—50-year evolution of liver transplantation. Transplant Int 31:1293–1317. https://doi.org/10.1111/tri.13358
Williams R, Ashton K, Aspinall R, Bellis MA, Bosanquet J, Cramp ME, Day N, Dhawan A, Dillon J, Dyson J et al (2015) Implementation of the lancet standing commission on liver disease in the UK. The Lancet 386:2098–2111. https://doi.org/10.1016/S0140-6736(15)00680-7
Jochmans I, van Rosmalen M, Pirenne J, Samuel U (2017) Adult liver allocation in Eurotransplant. Transplantation 101:1542–1550. https://doi.org/10.1097/TP.0000000000001631
Tullius SG, Rabb H (2018) Improving the supply and quality of deceased-donor organs for transplantation. N Engl J Med 378:1920–1929. https://doi.org/10.1056/NEJMra1507080
Pandya K, Sastry V, Panlilio MT, Yip TCF, Salimi S, West C, Virtue S, Wells M, Crawford M, Pulitano C et al (2020) Differential impact of extended criteria donors after brain death or circulatory death in adult liver transplantation. Liver Transplant 26:1603–1617. https://doi.org/10.1002/lt.25859
Ploeg RJ, D’alessandro AM, Knechtle SJ, Stegall MD, Pirsch JD, Hoffmann RM, Sasaki T, Sollinger HW, Belzer FO, Kalayoglu M (1993) Risk factors for primary dysfunction after liver transplantation—a multivariate analysis. Transplantation 55:807–813. https://doi.org/10.1097/00007890-199304000-00024
Jay CL, Lyuksemburg V, Ladner DP, Wang E, Caicedo JC, Holl JL, Abecassis MM, Skaro AI (2011) Ischemic cholangiopathy after controlled donation after cardiac death liver transplantation: a meta-analysis. Ann Surg 253:259–264. https://doi.org/10.1097/SLA.0b013e318204e658
Dutkowski P, Oberkofler CE, Slankamenac K, Puhan MA, Schadde E, Müllhaupt B, Geier A, Clavien PA (2011) 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 254:745–754. https://doi.org/10.1097/SLA.0b013e3182365081
Marcon F, Schlegel A, Bartlett DC, Kalisvaart M, Bishop D, Mergental H, Roberts KJ, Mirza DF, Isaac J, Muiesan P et al (2018) Utilization of declined liver grafts yields comparable transplant outcomes and previous decline should not be a deterrent to graft use. Transplantation 102:e211–e218. https://doi.org/10.1097/TP.0000000000002127
Dar WA, Sullivan E, Bynon JS, Eltzschig H, Ju C (2019) Ischaemia reperfusion injury in liver transplantation: cellular and molecular mechanisms. Liver Int 39:788–801. https://doi.org/10.1111/liv.14091
Bellini MI, Nozdrin M, Yiu J, Papalois V (2019) Machine perfusion for abdominal organ preservation: a systematic review of kidney and liver human grafts. JCM 8:1221. https://doi.org/10.3390/jcm8081221
Mergental H, Perera MTPR, Laing RW, Muiesan P, Isaac JR, Smith A, Stephenson BTF, Cilliers H, Neil DAH, Hübscher SG et al (2016) Transplantation of declined liver allografts following normothermic ex-situ evaluation. Am J Transplant 16:3235–3245. https://doi.org/10.1111/ajt.13875
Mergental H, Stephenson BTF, Laing RW, Kirkham AJ, Neil DAH, Wallace LL, Boteon YL, Widmer J, Bhogal RH, Perera MTPR et al (2018) Development of clinical criteria for functional assessment to predict primary nonfunction of high-risk livers using normothermic machine perfusion. Liver Transplant 24:1453–1469. https://doi.org/10.1002/lt.25291
Tchilikidi KY (2019) Liver graft preservation methods during cold ischemia phase and normothermic machine perfusion. WJGS 11:126–142. https://doi.org/10.4240/wjgs.v11.i3.126
Matton APM, de Vries Y, Burlage LC, van Rijn R, Fujiyoshi M, de Meijer VE, de Boer MT, de Kleine RHJ, Verkade HJ, Gouw ASH et al (2019) Biliary bicarbonate, pH, and glucose are suitable biomarkers of biliary viability during ex situ normothermic machine perfusion of human donor livers. Transplantation 103:1405–1413. https://doi.org/10.1097/TP.0000000000002500
Mergental H, Laing RW, Kirkham AJ, Perera MTPR, Boteon YL, Attard J, Barton D, Curbishley S, Wilkhu M, Neil DAH et al (2020) Transplantation of discarded livers following viability testing with normothermic machine perfusion. Nat Commun 11:2939. https://doi.org/10.1038/s41467-020-16251-3
Melandro F, De Simone P, Ghinolfi D (2021) Viability testing during normothermic machine perfusion requires both hepatocellular and cholangiocellular criteria. Updates Surg 73:781–783. https://doi.org/10.1007/s13304-021-00976-x
Detry O, Le Dinh H, Noterdaeme T, De Roover A, Honoré P, Squifflet J-P, Meurisse M (2012) Categories of donation after cardiocirculatory death. Transplant Proc 44:1189–1195. https://doi.org/10.1016/j.transproceed.2012.05.001
Eurotransplant Manual - Eurotransplant Available online: https://www.eurotransplant.org/patients/eurotransplant-manual/ (accessed on 25 May 2021).
Cillo U, Burra P, Mazzaferro V, Belli L, Pinna AD, Spada M, Nannicosta A, Toniutto P, on behalf of the I-BELT (Italian Board of Experts in the Field of Liver Transplantation) (2015) A multistep, consensus-based approach to organ allocation in liver transplantation: toward a “Blended Principle Model”: consensus conference on liver allocation. Am J Transp 15:2552–2561. https://doi.org/10.1111/ajt.13408
De Carlis R, Schlegel A, Frassoni S, Olivieri T, Ravaioli M, Camagni S, Patrono D, Bassi D, Pagano D, Di Sandro S et al (2021) How to preserve liver grafts from circulatory death with long warm ischemia? A retrospective Italian cohort study with normothermic regional perfusion and hypothermic oxygenated perfusion. Transplantation. https://doi.org/10.1097/TP.0000000000003595 (Publish Ahead of Print)
Sutton ME, op den Dries S, Karimian N, Weeder PD, de Boer MT, Wiersema-Buist J, Gouw ASH, Leuvenink HGD, Lisman T, Porte RJ (2014) Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion. PLoS One 9:e110642. https://doi.org/10.1371/journal.pone.0110642
Di Francesco F, Pagano D, Martucci G, Gruttadauria S (2017) Normothermic machine perfusion using an air/oxygen mixer for reconditioning a liver from a marginal brain death donor: letter to the editor. Artif Organs 41:E66–E68. https://doi.org/10.1111/aor.12964
Di Francesco F, Pagano D, Martucci G, Cintorino D, Gruttadauria S (2019) Normothermic machine perfusion in liver transplantation: feasibility and promise of avoiding recooling before engrafting. Liver Transplant 25:1113–1117. https://doi.org/10.1002/lt.25473
op den Dries S, Karimian N, Sutton ME, Westerkamp AC, Nijsten MWN, Gouw ASH, Wiersema-Buist J, Lisman T, Leuvenink HGD, Porte RJ (2013) Ex vivo normothermic machine perfusion and viability testing of discarded human donor livers: normothermic perfusion of human livers. Am J Transplant 13:1327–1335. https://doi.org/10.1111/ajt.12187
van Rijn R, Schurink IJ, de Vries Y, van den Berg AP, Cortes Cerisuelo M, Darwish Murad S, Erdmann JI, Gilbo N, de Haas RJ, Heaton N et al (2021) Hypothermic machine perfusion in liver transplantation—a randomized trial. N Engl J Med 384:1391–1401. https://doi.org/10.1056/NEJMoa2031532
Dindo D, Demartines N, Clavien P-A (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213. https://doi.org/10.1097/01.sla.0000133083.54934.ae
Kwong AJ, Kim WR, Lake JR, Smith JM, Schladt DP, Skeans MA, Noreen SM, Foutz J, Booker SE, Cafarella M et al (2021) OPTN/SRTR 2019 annual data report: liver. Am J Transplant 21:208–315. https://doi.org/10.1111/ajt.16494
NHS Blood and Transplant Annual Report on Liver Transplantation 2019/2020. Available online: https://nhsbtdbe.blob.core.windows.net/umbraco-assets-corp/19867/nhsbt-liver-transplant-report-1920.pdf (accessed on 25 May 2021)
Kim WR, Lake JR, Smith JM, Schladt DP, Skeans MA, Harper AM, Wainright JL, Snyder JJ, Israni AK, Kasiske BL (2018) OPTN/SRTR 2016 annual data report: liver. Am J Transplant 18:172–253. https://doi.org/10.1111/ajt.14559
NHS Blood and Transplant Annual Report on Liver Transplantation 2016/2017. Available online: https://nhsbtdbe.blob.core.windows.net/umbraco-assets-corp/5007/annual_liver_transplantation_report_2017.pdf (accessed on 25 May 2021)
Ravaioli M, De Pace V, Angeletti A, Comai G, Vasuri F, Baldassarre M, Maroni L, Odaldi F, Fallani G, Caraceni P et al (2020) Hypothermic oxygenated new machine perfusion system in liver and kidney transplantation of extended criteria donors: first Italian clinical trial. Sci Rep 10:6063. https://doi.org/10.1038/s41598-020-62979-9
Centro Nazionale Trapianti - Istituto Superiore di Sanità Attività Di Donazione e Trapianto Di Organi, Tessuti e Cellule Staminali Emopoietiche - Sintesi Del Report 2020 Available online: http://www.trapianti.salute.gov.it/imgs/C_17_cntPubblicazioni_400_allegato.pdf (accessed on 25 May 2021)
Marrone G, Crinò F, Caruso S, Mamone G, Carollo V, Milazzo M, Gruttadauria S, Luca A, Gridelli B (2012) Multidisciplinary imaging of liver hydatidosis. WJG 18:1438. https://doi.org/10.3748/wjg.v18.i13.1438
Gruttadauria S, Saint Georges Chaumet M, Pagano D, Marsh JW, Bartoccelli C, Cintorino D, Arcadipane A, Vizzini G, Spada M, Gridelli B (2011) Impact of blood transfusion on early outcome of liver resection for colorectal hepatic metastases: blood transfusion on liver resection. J Surg Oncol 103:140–147. https://doi.org/10.1002/jso.21796
Laing RW, Mergental H, Mirza DF (2017) Normothermic ex-situ liver preservation: the new gold standard. Curr Opin Organ Transplant 22:274–280. https://doi.org/10.1097/MOT.0000000000000414
Reddy SP, Bhattacharjya S, Maniakin N, Greenwood J, Guerreiro D, Hughes D, Imber CJ, Pigott DW, Fuggle S, Taylor R et al (2004) Preservation of porcine non–heart-beating donor livers by sequential cold storage and warm perfusion. Transplantation 77:1328–1332. https://doi.org/10.1097/01.TP.0000119206.63326.56
Oniscu GC, Randle LV, Muiesan P, Butler AJ, Currie IS, Perera MTPR, Forsythe JL, Watson CJE (2014) In situ normothermic regional perfusion for controlled donation after circulatory death-the united kingdom experience: NRP in controlled DCD donation. Am J Transplant 14:2846–2854. https://doi.org/10.1111/ajt.12927
Ghinolfi D, Lai Q, Dondossola D, De Carlis R, Zanierato M, Patrono D, Baroni S, Bassi D, Ferla F, Lauterio A et al (2020) Machine perfusions in liver transplantation: the evidence-based position paper of the Italian society of organ and tissue transplantation. Liver Transplant 26:1298–1315. https://doi.org/10.1002/lt.25817
No funds, grants, or other support was received.
Conflict of interest
The authors have no relevant financial or non-financial interests to disclose.
Research involving human participant and/or animals
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Institutional Research Review Board of ISMETT (protocol code IRRB/44/16).
Informed consent statement
Informed consent was obtained from all patients involved in the study.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Below is the link to the electronic supplementary material.
About this article
Cite this article
Seidita, A., Longo, R., Di Francesco, F. et al. The use of normothermic machine perfusion to rescue liver allografts from expanded criteria donors. Updates Surg (2021). https://doi.org/10.1007/s13304-021-01169-2
- Liver transplantation
- Normothermic machine perfusion
- Hypothermic machine perfusion
- Expanded criteria donors
- Graft viability