[en] [en] BACKGROUND AND AIM: Liver graft utilization rates are a hot topic due to the worldwide organ shortage and an increasing number of transplant candidates on waiting lists. Liver perfusion techniques have been introduced in several countries, and may help to increase the organ supply, as they potentially allow the assessment of livers before use.
METHODS: Liver offers were counted from donation after circulatory death (DCD) donors (Maastricht-type-III) arising during the past decade in eight countries, including Belgium, France, Italy, the Netherlands, Spain, Switzerland, UK, and US. Initial DCD-type-III liver offers were correlated with accepted, recovered and implanted livers.
RESULTS: A total number of 34`269 DCD livers were offered, resulting in 9`780 liver transplants (28.5%). The discard rates were highest in UK and US, ranging between 70 and 80%. In contrast, much lower DCD liver discard rates, e.g., between 30-40%, were found in Belgium, France, Italy, Spain and Switzerland. In addition, large differences were recognized in the use of various machine perfusion techniques, and in terms of risk factors in the cohorts of implanted livers. For example, the median donor age and functional donor warm ischemia were highest in Italy, e.g., >40minutes, followed by Switzerland, France, and the Netherlands. Importantly, such varying risk profiles of accepted DCD livers between countries did not translate into large differences in five-year graft survival rates, which ranged between 60-82% in this analysis.
CONCLUSIONS: We highlight a significant number of discarded and consequently unused DCD liver offers. Countries with more routine use of in- and ex-situ machine perfusion strategies showed better DCD utilization rates without compromised outcome.
IMPACT AND IMPLICATIONS: A significant number of Maastricht type III DCD livers are discarded across Europe and North America today. The overall utilization rate among eight Western countries is 28.5%, but varies significantly between 18.9% and 74.2%. For example, the median DCD III liver utilization in five countries, e.g., Belgium, France, Italy, Switzerland, and Spain is 65%, in contrast to 24% in the Netherlands, UK and US. Despite this, and despite different rules and strategies for organ acceptance and preservation, the one and five-year graft survival remains currently relatively comparable among all participating countries. Factors which impact on DCD liver acceptance rates include the national pre-selections of donors, before the offer is made, as well as cutoffs for key risk factors, including donor age and donor warm ischemia time. In addition, a highly varying experience with modern machine perfusion technology is noticed. In situ and ex situ liver perfusion concepts, and assessment tools for type III DCD livers before transplantation may be one key part for the observed differences in better DCD III utilization.
Disciplines :
Surgery Gastroenterology & hepatology
Author, co-author :
Eden, Janina ; Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
Da Silva, Richard Sousa ; Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
Cortes-Cerisuelo, Miriam; Institute of Liver Studies, King's College Hospital, London, United Kingdom
Croome, Kristopher; Department of Transplant, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL 32224 United States
De Carlis, Riccardo ; Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
Hessheimer, Amelia J ; Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, CIBERehd, Madrid, Spain
Muller, Xavier ; Department of Digestive Surgery & Liver Transplantation, Croix-Rousse Hospital, University of Lyon I, Lyon, France
de Goeij, Femke ; Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
Banz, Vanessa; Department of Visceral Surgery and Medicine, Inselspital, Berne University Hospital, University of Berne, Berne, Switzerland
Magini, Giulia ; Division of Transplantation, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
Compagnon, Philippe; Division of Transplantation, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
Elmer, Andreas; Swisstransplant, The Swiss National Foundation for Organ Donation and Transplantation Effingerstrasse 1, 3011 Bern, Switzerland
Lauterio, Andrea ; Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy, Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy
Panconesi, Rebecca; General Surgery 2U-Liver Transplant Unit, Department of Surgery, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, 10124 Turin, Italy
Widmer, Jeannette ; Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
Dondossola, Daniele ; General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico and University of Milan, Centre of Preclinical Research, 20122, Italy
Muiesan, Paolo; General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico and University of Milan, Centre of Preclinical Research, 20122, Italy
Monbaliu, Diethard; Department of Microbiology, Immunology and Transplantation, Transplantation Research Group, Lab of Abdominal Transplantation, KU Leuven, Belgium, Department of Abdominal Transplantation, University Hospitals Leuven, Leuven, Belgium
de Rosner van Rosmalen, Marieke; Eurotransplant International Foundation, Leiden, the Netherlands
Detry, Olivier ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chirurgie abdo, sénologique, endocrine et de transplantation
Fondevila, Constantino ; Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, CIBERehd, Madrid, Spain
Jochmans, Ina ; Department of Microbiology, Immunology and Transplantation, Transplantation Research Group, Lab of Abdominal Transplantation, KU Leuven, Belgium, Department of Abdominal Transplantation, University Hospitals Leuven, Leuven, Belgium
Pirenne, Jacques ; Department of Microbiology, Immunology and Transplantation, Transplantation Research Group, Lab of Abdominal Transplantation, KU Leuven, Belgium, Department of Abdominal Transplantation, University Hospitals Leuven, Leuven, Belgium
Immer, Franz; Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy
Oniscu, Gabriel C; Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
de Jonge, Jeroen; Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
Lesurtel, Mickaël ; Department of HPB Surgery and Liver Transplantation, Beaujon Hospital, University of Paris Cité, 100 Bd du Général Leclerc, 92110, Clichy, France
De Carlis, Luciano G ; Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy, Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy
Taner, C Burcin ; Department of Transplant, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL 32224 United States
Heaton, Nigel; Institute of Liver Studies, King's College Hospital, London, United Kingdom
Schlegel, Andrea ; Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland, General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico and University of Milan, Centre of Preclinical Research, 20122, Italy
Dutkowski, Philipp; Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland. Electronic address: philipp.dutkowski@usz.ch
Paterno, F., Guarrera, J.V., Wima, K., Diwan, T., Cuffy, M.C., Anwar, N., et al. Clinical implications of donor warm and cold ischemia time in donor after circulatory death liver transplantation. Liver Transpl 25 (2019), 1342–1352.
Orman, E.S., Mayorga, M.E., Wheeler, S.B., Townsley, R.M., Toro-Diaz, H.H., Hayashi, P.H., et al. Declining liver graft quality threatens the future of liver transplantation in the United States. Liver Transplant 21 (2015), 1040–1050.
Muller, X., Schlegel, A., Kron, P., Eshmuminov, D., Wurdinger, M., Meierhofer, D., et al. Novel real-time prediction of liver graft function during hypothermic oxygenated machine perfusion before liver transplantation. Ann Surg 270 (2019), 783–790.
Marcon, F., Schlegel, A., Bartlett, D.C., Kalisvaart, M., Bishop, D., Mergental, H., et al. Utilization of declined liver grafts yields comparable transplant outcomes and previous decline should not Be a deterrent to graft use. Transplantation 102 (2018), E211–E218.
Schlegel, A., Foley, D.P., Savier, E., Flores Carvalho, M., De Carlis, L., Heaton, N., et al. Recommendations for donor and recipient selection and risk prediction: working Group report from the ILTS consensus conference in DCD liver transplantation. Transplantation 105 (2021), 1892–1903.
Fayek, S.A., Quintini, C., Chavin, K.D., Marsh, C.L., The current state of liver transplantation in the United States perspective from American society of transplant surgeons (ASTS) scientific Studies committee and endorsed by ASTS council. Am J Transplant 16 (2016), 3093–3104.
Jochmans, I., van Rosmalen, M., Pirenne, J., Samuel, U., Adult liver allocation in eurotransplant. Transplantation 101 (2017), 1542–1550.
Hobeika, M.J., Menser, T., Nguyen, D.T., Beal, L.L., Zajac, S., Graviss, E.A., United States donation after circulatory death liver transplantation is driven by a few high-utilization transplant centers. Am J Transplant 20 (2020), 320–321.
De Carlis, R., Schlegel, A., Frassoni, S., Olivieri, T., Ravaioli, M., Camagni, S., et al. 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 105 (2021), 2385–2396.
Monbaliu, D., Pirenne, J., Talbot, D., Liver transplantation using donation after cardiac death donors. J Hepatol 56 (2012), 474–485.
Fugate, J.E., Stadtler, M., Rabinstein, A.A., Wijdicks, E.F.M., Variability in donation after cardiac death protocols: a national survey. Transplantation 91 (2011), 386–389.
Dutkowski, P., Schlegel, A., de Oliveira, M., Mullhaupt, B., Neff, F., Clavien, P.A., HOPE for human liver grafts obtained from donors after cardiac death. J Hepatol 60 (2014), 765–772.
De Carlis, L., De Carlis, R., Muiesan, P., Past, present, and future of donation after circulatory death in Italy. Updates Surg 71 (2019), 7–9.
Hessheimer, A.J., Gastaca, M., Minambres, E., Colmenero, J., Fondevila, C., In representation of the SWGoDCD. Donation after circulatory death liver transplantation: consensus statements from the Spanish Liver Transplantation Society. Transpl Int 33 (2020), 902–916.
Dutkowski, P., Polak, W.G., Muiesan, P., Schlegel, A., Verhoeven, C.J., Scalera, I., et al. First comparison of hypothermic oxygenated PErfusion versus static cold storage of human donation after cardiac death liver transplants an international-matched case analysis. Ann Surg 262 (2015), 764–771.
Reich, D.J., Mulligan, D.C., Abt, P.L., Pruett, T.L., Abecassis, M.M., D'Alessandro, A., et al. ASTS recommended practice guidelines for controlled donation after cardiac death organ procurement and transplantation. Am J Transpl 9 (2009), 2004–2011.
Neuberger, J., Callaghan, C., Organ utilization - the next hurdle in transplantation?. Transpl Int 33 (2020), 1597–1609.
Schlegel, A., van Reeven, M., Croome, K., Parente, A., Dolcet, A., Widmer, J., et al. A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation. J Hepatol, 2021.
Schlegel, A., Muller, X., Kalisvaart, M., Muellhaupt, B., Perera, M.T.P.R., Isaac, J.R., et al. Outcomes of DCD liver transplantation using organs treated by hypothermic oxygenated perfusion before implantation. J Hepatol 70 (2019), 50–57.
Johnston, C.J.C., Sherif, A.E., Oniscu, G.C., Transplantation of discarded livers: the complementary role of normothermic regional perfusion. Nat Commun, 12, 2021.
Jochmans, I., Hessheimer, A.J., Neyrinck, A.P., Paredes, D., Bellini, M.I., Dark, J.H., et al. Consensus statement on normothermic regional perfusion in donation after circulatory death: report from the European Society for Organ Transplantation's Transplant Learning Journey. Transpl Int 34 (2021), 2019–2030.
Jakobsson, B., [Film about sister lena–a source for discussion]. Vardfacket 12 (1988), 24–27.
Schurink, I.J., van de Leemkolk, F.E.M., Fondevila, C., De Carlis, R., Savier, E., Oniscu, G.C., et al. Donor eligibility criteria and liver graft acceptance criteria during normothermic regional perfusion: a systematic review. Liver Transpl, 2022.
Escartin, A., Castro, E., Dopazo, C., Bueno, J., Bilbao, I., Margarit, C., Analysis of discarded livers for transplantation. Transplant Proc 37 (2005), 3859–3860.
de Boer, J.D., Putter, H., Blok, J.J., Cambridge, N.A., van den Berg, S.D., Vogelaar, S., et al. Development of the eurotransplant discard risk index to predict acceptance of livers for transplantation: a retrospective database analysis. Exp Clin Transplant 19 (2021), 1163–1172.
Panconesi, R., Flores Carvalho, M., Muiesan, P., Dutkowski, P., Schlegel, A., Liver perfusion strategies: what is best and do ischemia times still matter?. Curr Opin Organ Tran, 2022.
Schurink, I.J., de Goeij, F.H.C., Habets, L.J.M., van de Leemkolk, F.E.M., van Dun, C.A.A., Oniscu, G.C., et al. Salvage of declined extended-criteria DCD livers using in situ normothermic regional perfusion. Ann Surg 276 (2022), e223–e230.
Lozanovski, V.J., Dohler, B., Weiss, K.H., Mehrabi, A., Susal, C., The differential influence of cold ischemia time on outcome after liver transplantation for different indications-who is at risk? A collaborative transplant study report. Front Immunol, 11, 2020.
Adam, R., Cailliez, V., Majno, P., Karam, V., McMaster, P., Calne, R.Y., et al. Normalised intrinsic mortality risk in liver transplantation: European Liver Transplant Registry study. Lancet 356 (2000), 621–627.
Peters-Sengers, H., Houtzager, J.H.E., Idu, M.M., Heemskerk, M.B.A., van Heurn, E.L.W., van der Heide, J.J.H., et al. Impact of cold ischemia time on outcomes of deceased donor kidney transplantation: an analysis of a national registry. Transplant Direct, 5, 2019.
Antoine, C., Jasseron, C., Dondero, F., Savier, E., C FNSCD. Liver transplantation from controlled donors after circulatory death using normothermic regional perfusion: an initial French experience. Liver Transplant 26 (2020), 1516–1521.
van Leeuwen, O.B., Bruggenwirth, I.M.A., de Kleine, R.H.J., van den Berg, A.P., Verschuuren, E.A.M., Erasmus, M.E., et al. Machine perfusion of donation after circulatory death liver and lungs before combined liver-lung transplantation. Transplant Direct, 7, 2021.
Mueller, M., Kalisvaart, M., O'Rourke, J., Shetty, S., Parente, A., Muller, X., et al. Hypothermic oxygenated liver perfusion (HOPE) prevents tumor recurrence in liver transplantation from donation after circulatory death. Ann Surg 272 (2020), 759–765.
NHSBT Annual Report 2022. September 2022 cited; Available from: https://nhsbtdbe.blob.core.windows.net/umbraco-assets-corp/27814/nhsbt-liver-transplant-report-2122-final.pdf.
Swiss transplant annual report, 2021 cited; Available from: https://www.swisstransplant.org/fileadmin/user_upload/Dokumente/Jahresbericht/2021_Jahresbericht_Swisstransplant.pdf.
Eshmuminov, D., Becker, D., Bautista Borrego, L., Hefti, M., Schuler, M.J., Hagedorn, C., et al. An integrated perfusion machine preserves injured human livers for 1 week. Nat Biotechnol 38 (2020), 189–198.
Mergental, H., Laing, R.W., Kirkham, A.J., Perera, M.T.P.R., Boteon, Y.L., Attard, J., et al. Transplantation of discarded livers following viability testing with normothermic machine perfusion. Nat Commun, 11, 2020.
Watson, C.J.E., Gaurav, R., Fear, C., Swift, L., Selves, L., Ceresa, C.D.L., et al. Predicting early allograft function after normothermic machine perfusion. 2022, Transplantation.
van Leeuwen, O.B., Bodewes, S.B., Lantinga, V.A., Haring, M.P.D., Thorne, A.M., Bruggenwirth, I.M.A., et al. Sequential hypothermic and normothermic machine perfusion enables safe transplantation of high-risk donor livers. Am J Transpl 22 (2022), 1658–1670.
Thorne, A.M., Ubbink, R., Bruggenwirth, I.M.A., Nijsten, M.W., Porte, R.J., de Meijer, V.E., Hyperthermia-induced changes in liver physiology and metabolism: a rationale for hyperthermic machine perfusion. Am J Physiology-Gastrointestinal Liver Physiol 319 (2020), G43–G50.
Schlegel, A., Muller, X., Mueller, M., Stepanova, A., Kron, P., de Rougemont, O., et al. Hypothermic oxygenated perfusion protects from mitochondrial injury before liver transplantation. Ebiomedicine, 60, 2020.
Wang, L., Thompson, E., Bates, L., Pither, T.L., Hosgood, S.A., Nicholson, M.L., et al. Flavin mononucleotide as a biomarker of organ quality-A pilot study. Transplant Direct, 6, 2020.
Panconesi, R., Flores Carvalho, M., Mueller, M., Meierhofer, D., Dutkowski, P., Muiesan, P., et al. Viability assessment in liver transplantation-what is the impact of dynamic organ preservation?. Biomedicines, 9, 2021.
Watson, C.J.E., Hunt, F., Messer, S., Currie, I., Large, S., Sutherland, A., et al. In situ normothermic perfusion of livers in controlled circulatory death donation may prevent ischemic cholangiopathy and improve graft survival. Am J Transpl 19 (2019), 1745–1758.
Savier, E., Lim, C., Rayar, M., Orlando, F., Boudjema, K., Mohkam, K., et al. Favorable outcomes of liver transplantation from controlled circulatory death donors using normothermic regional perfusion compared to brain death donors. Transplantation 104 (2020), 1943–1951.
