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3. Prolonged hypothermic machine perfusion enables daytime liver transplantation – an IDEAL stage 2 prospective clinical trial

Author

de Meijer, Vincent E., Brüggenwirth, Isabel M.A., Lantinga, Veerle A., Moers, Cyril, Monbaliu, Diethard, Hofker, Sijbrand H., Bottema, Jan, Franke, Hildegaard S., de Boer, Marieke T., van den Boom, Anne Loes, Buis, Carlijn I., Fouraschen, Suomi M.G., Hoogwater, Frederik J.H., Klaase, Joost M., de Kleine, Ruben H.J., Meerdink, Mark, Nijkamp, Maarten W., Porte, Robert J., Rayar, A. Michel, van den Berg, Aad P., Blokzijl, Hans, Cuperus, Frans J.C., van der Heide, Frans, van Vilsteren, Frederike G.I., Abbasova, Ilhama F., Fernhout, Meine H., Meyer, Peter, Muskiet, Ernesto R.R., Reyntjens, Koen M.E.M., Vos, Jaap J., Zeillemaker, Miriam, Haring, Martijn P.D., Lascaris, Bianca, Pamplona, Carol C., Thorne, Adam M., Veenma, Vivianne, van Leeuwen, Otto B., Bodewes, Silke B., Lisman, Ton, Adelmeijer, Jelle, Wiersema-Buist, Janneke, van den Heuvel, Marius, and de Kleine, Ruben H.

Published
2024
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5. Prolonged hypothermic machine perfusion enables daytime liver transplantation – an IDEAL stage 2 prospective clinical trial

Author

Brüggenwirth, Isabel M.A., primary, Lantinga, Veerle A., additional, Lascaris, Bianca, additional, Thorne, Adam M., additional, Meerdink, Mark, additional, de Kleine, Ruben H., additional, Blokzijl, Hans, additional, van den Berg, Aad P., additional, Reyntjens, Koen M.E.M., additional, Lisman, Ton, additional, Porte, Robert J., additional, de Meijer, Vincent E., additional, Brüggenwirth, Isabel M.A., additional, Moers, Cyril, additional, Monbaliu, Diethard, additional, Hofker, Sijbrand H., additional, Bottema, Jan, additional, Franke, Hildegaard S., additional, de Boer, Marieke T., additional, van den Boom, Anne Loes, additional, Buis, Carlijn I., additional, Fouraschen, Suomi M.G., additional, Hoogwater, Frederik J.H., additional, Klaase, Joost M., additional, de Kleine, Ruben H.J., additional, Nijkamp, Maarten W., additional, Rayar, A. Michel, additional, Cuperus, Frans J.C., additional, van der Heide, Frans, additional, van Vilsteren, Frederike G.I., additional, Abbasova, Ilhama F., additional, Fernhout, Meine H., additional, Meyer, Peter, additional, Muskiet, Ernesto R.R., additional, Vos, Jaap J., additional, Zeillemaker, Miriam, additional, Haring, Martijn P.D., additional, Pamplona, Carol C., additional, Veenma, Vivianne, additional, van Leeuwen, Otto B., additional, Bodewes, Silke B., additional, Adelmeijer, Jelle, additional, Wiersema-Buist, Janneke, additional, and van den Heuvel, Marius, additional

Published
2024
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6. Novel Benchmark Values for Redo Liver Transplantation: Does the Outcome Justify the Effort?

Author

Abbassi, Fariba, Gero, Daniel, Muller, Xavier, Bueno, Alba, Figiel, Wojciech, Robin, Fabien, Laroche, Sophie, Picard, Benjamin, Shankar, Sadhana, Ivanics, Tommy, van Reeven, Marjolein, van Leeuwen, Otto B., Braun, Hillary J., Monbaliu, Diethard, Breton, Antoine, Vachharajani, Neeta, Bonaccorsi Riani, Eliano, Nowak, Greg, McMillan, Robert R., Abu-Gazala, Samir, Nair, Amit, Bruballa, Rocio, Paterno, Flavio, Weppler Sears, Deborah, Pinna, Antonio D., Guarrera, James V., de Santibañes, Eduardo, de Santibañes, Martin, Hernandez-Alejandro, Roberto, Olthoff, Kim, Ghobrial, R Mark, Ericzon, Bo-Göran, Ciccarelli, Olga, Chapman, William C., Mabrut, Jean-Yves, Pirenne, Jacques, Müllhaupt, Beat, Ascher, Nancy L., Porte, Robert J., de Meijer, Vincent E., Polak, Wojciech G., Sapisochin, Gonzalo, Attia, Magdy, Soubrane, Olivier, Weiss, Emmanuel, Adam, René A., Cherqui, Daniel, Boudjema, Karim, Zieniewicz, Krzysztof, Jassem, Wayel, Dutkowski, Philipp, and Clavien, Pierre-Alain

Published
2022
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11. Restoration of Bile Duct Injury of Donor Livers During Ex Situ Normothermic Machine Perfusion

Author

de Jong, Iris E.M., primary, Bodewes, Silke B., additional, van Leeuwen, Otto B., additional, Oosterhuis, Dorenda, additional, Lantinga, Veerle A., additional, Thorne, Adam M., additional, Lascaris, Bianca, additional, van den Heuvel, Marius C., additional, Wells, Rebecca G., additional, Olinga, Peter, additional, de Meijer, Vincent E., additional, and Porte, Robert J., additional

Published
2023
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12. Transplantation of High-risk Donor Livers After Ex Situ Resuscitation and Assessment Using Combined Hypo- and Normothermic Machine Perfusion: A Prospective Clinical Trial

Author

van Leeuwen, Otto B., de Vries, Yvonne, Fujiyoshi, Masato, Nijsten, Maarten W. N., Ubbink, Rinse, Pelgrim, Gert Jan, Werner, Maureen J. M., Reyntjens, Koen M. E. M., van den Berg, Aad P., de Boer, Marieke T., de Kleine, Ruben H. J., Lisman, Ton, de Meijer, Vincent E., and Porte, Robert J.

Published
2019
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13. Restoration of Bile Duct Injury of Donor Livers During Ex Situ Normothermic Machine Perfusion

Author

De Jong, Iris E.M., Bodewes, Silke B., Van Leeuwen, Otto B., Oosterhuis, Dorenda, Lantinga, Veerle A., Thorne, Adam M., Lascaris, Bianca, Van Den Heuvel, Marius C., Wells, Rebecca G., Olinga, Peter, De Meijer, Vincent E., Porte, Robert J., De Jong, Iris E.M., Bodewes, Silke B., Van Leeuwen, Otto B., Oosterhuis, Dorenda, Lantinga, Veerle A., Thorne, Adam M., Lascaris, Bianca, Van Den Heuvel, Marius C., Wells, Rebecca G., Olinga, Peter, De Meijer, Vincent E., and Porte, Robert J.

Abstract

Background. End-ischemic ex situ normothermic machine perfusion (NMP) enables assessment of donor livers prior to transplantation. The objective of this study was to provide support for bile composition as a marker of biliary viability and to investigate whether bile ducts of high-risk human donor livers already undergo repair during NMP. Methods. Forty-two livers that were initially declined for transplantation were included in our NMP clinical trial. After NMP, livers were either secondary declined (n = 17) or accepted for transplantation (n = 25) based on the chemical composition of bile and perfusate samples. Bile duct biopsies were taken before and after NMP and assessed using an established histological injury severity scoring system and a comprehensive immunohistochemical assessment focusing on peribiliary glands (PBGs), vascular damage, and regeneration. Results. Bile ducts of livers that were transplanted after viability testing during NMP showed better preservation of PBGs, (micro)vasculature, and increased cholangiocyte proliferation, compared with declined livers. Biliary bicarbonate, glucose, and pH were confirmed as accurate biomarkers of bile duct vitality. In addition, we found evidence of PBG-based progenitor cell differentiation toward mature cholangiocytes during NMP. Conclusions. Favorable bile chemistry during NMP correlates well with better-preserved biliary microvasculature and PBGs, with a preserved capacity for biliary regeneration. During NMP, biliary tree progenitor cells start to differentiate toward mature cholangiocytes, facilitating restoration of the ischemically damaged surface epithelium.

Published
2023

16. A Multicentre Outcome Analysis to Define Global Benchmarks for Donation after Circulatory Death Liver Transplantation

Author

Schlegel, Andrea, van Reeven, Marjolein, Croome, Kristopher, Parente, Alessandro, Dolcet, Annalisa, Widmer, Jeannette, Meurisse, Nicolas, De Carlis, Riccardo, Hessheimer, Amelia, Jochmans, Ina, Mueller, Matteo, van Leeuwen, Otto B, Nair, Amit, Tomiyama, Koji, Sherif, Ahmed, Elsharif, Mohamed, Kron, Philipp, van der Helm, Danny, Borja-Cacho, Daniel, Bohorquez, Humberto, Germanova, Desislava, Dondossola, Daniele, Olivieri, Tiziana, Camagni, Stefania, Gorgen, Andre, Patrono, Damiano, Cescon, Matteo, Croome, Sarah, Panconesi, Rebecca, Carvalho, Mauricio Flores, et al, and University of Zurich

Subjects
Hepatology, 610 Medicine & health, 2721 Hepatology, 10217 Clinic for Visceral and Transplantation Surgery
Published
2022

17. Novel Benchmark Values for Redo Liver Transplantation. Does the Outcome Justify the Effort?

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, Abbassi, Fariba, Gero, Daniel, Muller, Xavier, Bueno, Alba, Figiel, Wojciech, Robin, Fabien, Laroche, Sophie, Picard, Benjamin, Shankar, Sadhana, Ivanics, Tommy, van Reeven, Marjolein, van Leeuwen, Otto B, Braun, Hillary J, Monbaliu, Diethard, Breton, Antoine, Vachharajani, Neeta, Bonaccorsi Riani, Eliano, Nowak, Greg, McMillan, Robert R, Abu-Gazala, Samir, Nair, Amit, Bruballa, Rocio, Paterno, Flavio, Weppler Sears, Deborah, Pinna, Antonio D, Guarrera, James V, de Santibañes, Eduardo, de Santibañes, Martin, Hernandez-Alejandro, Roberto, Olthoff, Kim, Ghobrial, R Mark, Ericzon, Bo-Göran, Ciccarelli, Olga, Chapman, William C, Mabrut, Jean-Yves, Pirenne, Jacques, Müllhaupt, Beat, Ascher, Nancy L, Porte, Robert J, de Meijer, Vincent E, Polak, Wojciech G, Sapisochin, Gonzalo, Attia, Magdy, Weiss, Emmanuel, Adam, René A, Cherqui, Daniel, Boudjema, Karim, Zienewicz, Krzysztof, Jassem, Wayel, Dutkowski, Philipp, Clavien, Pierre-Alain, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, Abbassi, Fariba, Gero, Daniel, Muller, Xavier, Bueno, Alba, Figiel, Wojciech, Robin, Fabien, Laroche, Sophie, Picard, Benjamin, Shankar, Sadhana, Ivanics, Tommy, van Reeven, Marjolein, van Leeuwen, Otto B, Braun, Hillary J, Monbaliu, Diethard, Breton, Antoine, Vachharajani, Neeta, Bonaccorsi Riani, Eliano, Nowak, Greg, McMillan, Robert R, Abu-Gazala, Samir, Nair, Amit, Bruballa, Rocio, Paterno, Flavio, Weppler Sears, Deborah, Pinna, Antonio D, Guarrera, James V, de Santibañes, Eduardo, de Santibañes, Martin, Hernandez-Alejandro, Roberto, Olthoff, Kim, Ghobrial, R Mark, Ericzon, Bo-Göran, Ciccarelli, Olga, Chapman, William C, Mabrut, Jean-Yves, Pirenne, Jacques, Müllhaupt, Beat, Ascher, Nancy L, Porte, Robert J, de Meijer, Vincent E, Polak, Wojciech G, Sapisochin, Gonzalo, Attia, Magdy, Weiss, Emmanuel, Adam, René A, Cherqui, Daniel, Boudjema, Karim, Zienewicz, Krzysztof, Jassem, Wayel, Dutkowski, Philipp, and Clavien, Pierre-Alain

Abstract

To define benchmark cutoffs for redo liver transplantation (redo-LT). In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT. We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with MELD score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary non-function (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers. Out of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index (CCI®) at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks. This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This major analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.

Published
2022

18. A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation

Author

Schlegel, A, van Reeven, M, Croome, K, Parente, A, Dolcet, A, Widmer, J, Meurisse, N, De Carlis, R, Hessheimer, A, Jochmans, I, Mueller, M, van Leeuwen, O, Nair, A, Tomiyama, K, Sherif, A, Elsharif, M, Kron, P, van der Helm, D, Borja-Cacho, D, Bohorquez, H, Germanova, D, Dondossola, D, Olivieri, T, Camagni, S, Gorgen, A, Patrono, D, Cescon, M, Croome, S, Panconesi, R, Flores Carvalho, M, Ravaioli, M, Caicedo, J, Loss, G, Lucidi, V, Sapisochin, G, Romagnoli, R, Jassem, W, Colledan, M, De Carlis, L, Rossi, G, Di Benedetto, F, Miller, C, van Hoek, B, Attia, M, Lodge, P, Hernandez-Alejandro, R, Detry, O, Quintini, C, Oniscu, G, Fondevila, C, Malagó, M, Pirenne, J, Ijzermans, J, Porte, R, Dutkowski, P, Taner, C, Heaton, N, Clavien, P, Polak, W, Muiesan, P, Schlegel, Andrea, van Reeven, Marjolein, Croome, Kristopher, Parente, Alessandro, Dolcet, Annalisa, Widmer, Jeannette, Meurisse, Nicolas, De Carlis, Riccardo, Hessheimer, Amelia, Jochmans, Ina, Mueller, Matteo, van Leeuwen, Otto B, Nair, Amit, Tomiyama, Koji, Sherif, Ahmed, Elsharif, Mohamed, Kron, Philipp, van der Helm, Danny, Borja-Cacho, Daniel, Bohorquez, Humberto, Germanova, Desislava, Dondossola, Daniele, Olivieri, Tiziana, Camagni, Stefania, Gorgen, Andre, Patrono, Damiano, Cescon, Matteo, Croome, Sarah, Panconesi, Rebecca, Flores Carvalho, Mauricio, Ravaioli, Matteo, Caicedo, Juan Carlos, Loss, George, Lucidi, Valerio, Sapisochin, Gonzalo, Romagnoli, Renato, Jassem, Wayel, Colledan, Michele, De Carlis, Luciano, Rossi, Giorgio, Di Benedetto, Fabrizio, Miller, Charles M, van Hoek, Bart, Attia, Magdy, Lodge, Peter, Hernandez-Alejandro, Roberto, Detry, Olivier, Quintini, Cristiano, Oniscu, Gabriel C, Fondevila, Constantino, Malagó, Massimo, Pirenne, Jacques, IJzermans, Jan Nm, Porte, Robert J, Dutkowski, Philipp, Taner, C Burcin, Heaton, Nigel, Clavien, Pierre-Alain, Polak, Wojciech G, Muiesan, Paolo, Schlegel, A, van Reeven, M, Croome, K, Parente, A, Dolcet, A, Widmer, J, Meurisse, N, De Carlis, R, Hessheimer, A, Jochmans, I, Mueller, M, van Leeuwen, O, Nair, A, Tomiyama, K, Sherif, A, Elsharif, M, Kron, P, van der Helm, D, Borja-Cacho, D, Bohorquez, H, Germanova, D, Dondossola, D, Olivieri, T, Camagni, S, Gorgen, A, Patrono, D, Cescon, M, Croome, S, Panconesi, R, Flores Carvalho, M, Ravaioli, M, Caicedo, J, Loss, G, Lucidi, V, Sapisochin, G, Romagnoli, R, Jassem, W, Colledan, M, De Carlis, L, Rossi, G, Di Benedetto, F, Miller, C, van Hoek, B, Attia, M, Lodge, P, Hernandez-Alejandro, R, Detry, O, Quintini, C, Oniscu, G, Fondevila, C, Malagó, M, Pirenne, J, Ijzermans, J, Porte, R, Dutkowski, P, Taner, C, Heaton, N, Clavien, P, Polak, W, Muiesan, P, Schlegel, Andrea, van Reeven, Marjolein, Croome, Kristopher, Parente, Alessandro, Dolcet, Annalisa, Widmer, Jeannette, Meurisse, Nicolas, De Carlis, Riccardo, Hessheimer, Amelia, Jochmans, Ina, Mueller, Matteo, van Leeuwen, Otto B, Nair, Amit, Tomiyama, Koji, Sherif, Ahmed, Elsharif, Mohamed, Kron, Philipp, van der Helm, Danny, Borja-Cacho, Daniel, Bohorquez, Humberto, Germanova, Desislava, Dondossola, Daniele, Olivieri, Tiziana, Camagni, Stefania, Gorgen, Andre, Patrono, Damiano, Cescon, Matteo, Croome, Sarah, Panconesi, Rebecca, Flores Carvalho, Mauricio, Ravaioli, Matteo, Caicedo, Juan Carlos, Loss, George, Lucidi, Valerio, Sapisochin, Gonzalo, Romagnoli, Renato, Jassem, Wayel, Colledan, Michele, De Carlis, Luciano, Rossi, Giorgio, Di Benedetto, Fabrizio, Miller, Charles M, van Hoek, Bart, Attia, Magdy, Lodge, Peter, Hernandez-Alejandro, Roberto, Detry, Olivier, Quintini, Cristiano, Oniscu, Gabriel C, Fondevila, Constantino, Malagó, Massimo, Pirenne, Jacques, IJzermans, Jan Nm, Porte, Robert J, Dutkowski, Philipp, Taner, C Burcin, Heaton, Nigel, Clavien, Pierre-Alain, Polak, Wojciech G, and Muiesan, Paolo

Abstract

Background & Aims: The concept of benchmarking is established in the field of transplant surgery; however, benchmark values for donation after circulatory death (DCD) liver transplantation are not available. Thus, we aimed to identify the best possible outcomes in DCD liver transplantation and to propose outcome reference values. Methods: Based on 2,219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1,012 low-risk, primary, adult liver transplantations with a laboratory MELD score of ≤20 points, receiving a DCD liver with a total donor warm ischemia time of ≤30 minutes and asystolic donor warm ischemia time of ≤15 minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the comprehensive complication index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75th-percentile was considered. Results: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centres. The 1-year retransplant and mortality rates were 4.5% and 8.4% in the benchmark group, respectively. Within the first year of follow-up, 51.1% of recipients developed at least 1 major complication (≥Clavien-Dindo-Grade III). Benchmark cut-offs were ≤3 days and ≤16 days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade III), ≤16.8% for ischemic cholangiopathy, and ≤38.9 CCI points 1 year after transplant. Comparisons with higher risk groups showed more complications and impaired graft survival outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk. Conclusions: Despite excellent 1-year survival, morbidity in benchmark cases remains high. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk grou

Published
2022

19. A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation

Author

Schlegel, Andrea, primary, van Reeven, Marjolein, additional, Croome, Kristopher, additional, Parente, Alessandro, additional, Dolcet, Annalisa, additional, Widmer, Jeannette, additional, Meurisse, Nicolas, additional, De Carlis, Riccardo, additional, Hessheimer, Amelia, additional, Jochmans, Ina, additional, Mueller, Matteo, additional, van Leeuwen, Otto B., additional, Nair, Amit, additional, Tomiyama, Koji, additional, Sherif, Ahmed, additional, Elsharif, Mohamed, additional, Kron, Philipp, additional, van der Helm, Danny, additional, Borja-Cacho, Daniel, additional, Bohorquez, Humberto, additional, Germanova, Desislava, additional, Dondossola, Daniele, additional, Olivieri, Tiziana, additional, Camagni, Stefania, additional, Gorgen, Andre, additional, Patrono, Damiano, additional, Cescon, Matteo, additional, Croome, Sarah, additional, Panconesi, Rebecca, additional, Carvalho, Mauricio Flores, additional, Ravaioli, Matteo, additional, Caicedo, Juan Carlos, additional, Loss, George, additional, Lucidi, Valerio, additional, Sapisochin, Gonzalo, additional, Romagnoli, Renato, additional, Jassem, Wayel, additional, Colledan, Michele, additional, De Carlis, Luciano, additional, Rossi, Giorgio, additional, Di Benedetto, Fabrizio, additional, Miller, Charles M., additional, van Hoek, Bart, additional, Attia, Magdy, additional, Lodge, Peter, additional, Hernandez-Alejandro, Roberto, additional, Detry, Olivier, additional, Quintini, Cristiano, additional, Oniscu, Gabriel C., additional, Fondevila, Constantino, additional, Malagó, Massimo, additional, Pirenne, Jacques, additional, IJzermans, Jan N.M., additional, Porte, Robert J., additional, Dutkowski, Philipp, additional, Taner, C. Burcin, additional, Heaton, Nigel, additional, Clavien, Pierre-Alain, additional, Polak, Wojciech G., additional, Muiesan, Paolo, additional, Alwayn, Ian P.J., additional, van der Berg, Aad P., additional, Carbonaro, Margherita, additional, Claasen, Marco, additional, Daud, Amna, additional, de Meijer, Vincent E., additional, Metselaar, Herold J., additional, Monbaliu, Diethard, additional, Paolucci, Maite, additional, Vets, Sofie, additional, and Winter, Erin, additional

Published
2022
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21. Dual Versus Single Oxygenated Hypothermic Machine Perfusion of Porcine Livers: Impact on Hepatobiliary and Endothelial Cell Injury

Author

de Vries, Yvonne, primary, Brüggenwirth, Isabel M. A., additional, Karangwa, Shanice A., additional, von Meijenfeldt, Fien A., additional, van Leeuwen, Otto B., additional, Burlage, Laura C., additional, de Jong, Iris E. M., additional, Gouw, Annette S. H., additional, de Meijer, Vincent E., additional, Lisman, Ton, additional, and Porte, Robert J., additional

Published
2021
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25. Hypothermic Machine Perfusion in Liver Transplantation — A Randomized Trial

Author

van Rijn, Rianne, primary, Schurink, Ivo J., additional, de Vries, Yvonne, additional, van den Berg, Aad P., additional, Cortes Cerisuelo, Miriam, additional, Darwish Murad, Sarwa, additional, Erdmann, Joris I., additional, Gilbo, Nicholas, additional, de Haas, Robbert J., additional, Heaton, Nigel, additional, van Hoek, Bart, additional, Huurman, Volkert A.L., additional, Jochmans, Ina, additional, van Leeuwen, Otto B., additional, de Meijer, Vincent E., additional, Monbaliu, Diethard, additional, Polak, Wojciech G., additional, Slangen, Jules J.G., additional, Troisi, Roberto I., additional, Vanlander, Aude, additional, de Jonge, Jeroen, additional, and Porte, Robert J., additional

Published
2021
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27. Evaluation of Liver Graft Donation After Euthanasia.

Author

UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service de chirurgie et transplantation abdominale, van Reeven, Marjolein, Gilbo, Nicholas, Monbaliu, Diethard, van Leeuwen, Otto B, Porte, Robert J, Ysebaert, Dirk, van Hoek, Bart, Alwayn, Ian P J, Meurisse, Nicolas, Detry, Olivier, Coubeau, Laurent, Ciccarelli, Olga, Berrevoet, Frederik, Vanlander, Aude, IJzermans, Jan N M, Polak, Wojciech G, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service de chirurgie et transplantation abdominale, van Reeven, Marjolein, Gilbo, Nicholas, Monbaliu, Diethard, van Leeuwen, Otto B, Porte, Robert J, Ysebaert, Dirk, van Hoek, Bart, Alwayn, Ian P J, Meurisse, Nicolas, Detry, Olivier, Coubeau, Laurent, Ciccarelli, Olga, Berrevoet, Frederik, Vanlander, Aude, IJzermans, Jan N M, and Polak, Wojciech G

Abstract

IMPORTANCE: The option of donating organs after euthanasia is not well known. Assessment of the results of organ transplants with grafts donated after euthanasia is essential to justify the use of this type of organ donation. OBJECTIVES: To assess the outcomes of liver transplants (LTs) with grafts donated after euthanasia (donation after circulatory death type V [DCD-V]), and to compare them with the results of the more commonly performed LTs with grafts from donors with a circulatory arrest after the withdrawal of life-supporting treatment (type III [DCD-III]). DESIGN, SETTING, AND PARTICIPANTS: This retrospective multicenter cohort study analyzed medical records and LT data for most transplant centers in the Netherlands and Belgium. All LTs with DCD-V grafts performed from the start of the donation after euthanasia program (September 2012 for the Netherlands, and January 2005 for Belgium) through July 1, 2018, were included in the analysis. A comparative cohort of patients who received DCD-III grafts was also analyzed. All patients in both cohorts were followed up for at least 1 year. Data analysis was performed from September 2019 to December 2019. EXPOSURES: Liver transplant with either a DCD-V graft or DCD-III graft. MAIN OUTCOMES AND MEASURES: Primary outcomes were recipient and graft survival rates at years 1, 3, and 5 after the LT. Secondary outcomes included postoperative complications (early allograft dysfunction, hepatic artery thrombosis, and nonanastomotic biliary strictures) within the first year after the LT. RESULTS: Among the cohort of 47 LTs with DCD-V grafts, 25 organ donors (53%) were women and the median (interquartile range [IQR]) age was 51 (44-59) years. Among the cohort of 542 LTs with DCD-III grafts, 335 organ donors (62%) were men and the median (IQR) age was 49 (37-57) years. Median (IQR) follow-up was 3.8 (2.1-6.3) years. In the DCD-V cohort, 30 recipients (64%) were men, and the median (IQR) age was 56 (48-64) years. Recipient survival

Published
2020

29. Oxygenated versus non‐oxygenated flush out and storage of donor livers: An experimental study.

Author

Brüggenwirth, Isabel M. A., van der Plas, Willemijn S., van Leeuwen, Otto B., Thorne, Adam M., Rayar, Michel, de Meijer, Vincent E., and Porte, Robert J.

Subjects
FLAVIN mononucleotide, CELL-free DNA, LIVER, ADENOSINE triphosphate, REPERFUSION injury
Abstract

Background: During donor organ procurement and subsequent static cold storage (SCS), hepatic adenosine triphosphate (ATP) levels are progressively depleted, which contributes to ischemia‐reperfusion injury (IRI). We sought to investigate a simple approach to prevent ATP depletion and IRI using a porcine donation after circulatory death (DCD) liver reperfusion model. Methods: After 30 min warm ischemia, porcine livers were flushed via the portal vein with cold (4°C) non‐oxygenated University of Wisconsin (UW) preservation solution (n = 6, control group) or with oxygenated UW (n = 6, OxyFlush group). Livers were then subjected to 4 h SCS in non‐oxygenated (control) or oxygenated (OxyFlush) UW, followed by 4 h normothermic reperfusion using whole blood. Hepatic ATP levels were compared, and hepatobiliary function and injury were assessed. Results: At the end of SCS, ATP was higher in the OxyFlush group compared to controls (delta ATP of +0.26 vs. −0.68 µmol/g protein, p = 0.04). All livers produced bile and metabolized lactate, and there were no differences between the groups. Grafts in the OxyFlush group had lower blood glucose levels after reperfusion (p = 0.04). Biliary pH, glucose and bicarbonate were not different between the groups. Injury markers including liver transaminases, lactate dehydrogenase, malondialdehyde, cell‐free DNA and flavin mononucleotide in the SCS solution and during reperfusion were also similar. Histological assessment of the parenchyma and bile ducts did not reveal differences between the groups. Conclusion: Oxygenated flush out and storage of DCD porcine livers prevents ATP depletion during ischemia, but this does not seem sufficient to mitigate early signs of IRI. [ABSTRACT FROM AUTHOR]

Published
2022
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30. Pretransplant sequential hypo- and normothermic machine perfusion of suboptimal livers donated after circulatory death using a hemoglobin-based oxygen carrier perfusion solution

Author

de Vries, Yvonne, Matton, Alix P.M., Nijsten, Maarten W.N., Werner, Maureen J.M., van den Berg, Aad P., de Boer, Marieke T., Buis, Carlijn I., Fujiyoshi, Masato, de Kleine, Ruben H.J., van Leeuwen, Otto B., Meyer, Peter, van den Heuvel, Marius C., de Meijer, Vincent E., and Porte, Robert J.

Published
2019
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31. Evaluation of Liver Graft Donation After Euthanasia

Author

van Reeven, Marjolein, primary, Gilbo, Nicholas, additional, Monbaliu, Diethard, additional, van Leeuwen, Otto B., additional, Porte, Robert J., additional, Ysebaert, Dirk, additional, van Hoek, Bart, additional, Alwayn, Ian P. J., additional, Meurisse, Nicolas, additional, Detry, Olivier, additional, Coubeau, Laurent, additional, Cicarelli, Olga, additional, Berrevoet, Frederik, additional, Vanlander, Aude, additional, IJzermans, Jan N. M., additional, and Polak, Wojciech G., additional

Published
2020
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33. The First Case of Ischemia-Free Kidney Transplantation in Humans

Author

He, Xiaoshun, primary, Chen, Guodong, additional, Zhu, Zebin, additional, Zhang, Zhiheng, additional, Yuan, Xiaopeng, additional, Han, Ming, additional, Zhao, Qiang, additional, Zheng, Yitao, additional, Tang, Yunhua, additional, Huang, Shanzhou, additional, Wang, Linhe, additional, van Leeuwen, Otto B., additional, Wang, Xiaoping, additional, Chen, Chuanbao, additional, Mo, Liqiu, additional, Jiao, Xingyuan, additional, Li, Xianchang, additional, Wang, Changxi, additional, Huang, Jiefu, additional, Cui, Jun, additional, and Guo, Zhiyong, additional

Published
2019
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34. INCREASED AND SAFE UTILIZATION OF HIGH-RISK DONOR LIVERS FOR TRANSPLANTATION AFTER EX SITU RESUSCITATION AND ASSESSMENT USING SEQUENTIAL HYPO- AND NORMOTHERMIC MACHINE PERFUSION

Author

van Leeuwen, Otto B., deVries, Yvonne, Fujiyoshi, Masato, Ubbink, Rinse, Pelgrim, Gert Jan, Werner, Maureen J. M., Reyntjens, Koen M. E. M., vandenBerg, Aad P., deBoer, Marieke T., de Meijer, Vincent E., Porte, Robert J., Groningen Institute for Organ Transplantation (GIOT), and Center for Liver, Digestive and Metabolic Diseases (CLDM)

Published
2019

35. Transplantation of high-risk donor livers after resuscitation and viability assessment using a combined protocol of oxygenated hypothermic, rewarming and normothermic machine perfusion: study protocol for a prospective, single-arm study (DHOPE-COR-NMP trial)

Author

de Vries, Yvonne, primary, Berendsen, Tim A, additional, Fujiyoshi, Masato, additional, van den Berg, Aad P, additional, Blokzijl, Hans, additional, de Boer, Marieke T, additional, van der Heide, Frans, additional, de Kleine, Ruben H J, additional, van Leeuwen, Otto B, additional, Matton, Alix P M, additional, Werner, Maureen J M, additional, Lisman, Ton, additional, de Meijer, Vincent E, additional, and Porte, Robert, additional

Published
2019
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39. Hypothermic oxygenated machine perfusion reduces bile duct reperfusion injury after transplantation of donation after circulatory death livers

Author

van Rijn, Rianne, primary, van Leeuwen, Otto B., additional, Matton, Alix P. M., additional, Burlage, Laura C., additional, Wiersema‐Buist, Janneke, additional, van den Heuvel, Marius C., additional, de Kleine, Ruben H. J., additional, de Boer, Marieke T., additional, Gouw, Annette S. H., additional, and Porte, Robert J., additional

Published
2018
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41. Oxygen Transport during Ex Situ Machine Perfusion of Donor Livers Using Red Blood Cells or Artificial Oxygen Carriers.

Author

Bodewes, Silke B., van Leeuwen, Otto B., Thorne, Adam M., Lascaris, Bianca, Ubbink, Rinse, Lisman, Ton, Monbaliu, Diethard, De Meijer, Vincent E., Nijsten, Maarten W. N., and Porte, Robert J.

Subjects
*OXYGEN carriers, *ERYTHROCYTES, *BLOOD substitutes, *ARTIFICIAL cells, *PERFUSION, *OXYGEN
Abstract

Oxygenated ex situ machine perfusion of donor livers is an alternative for static cold preservation that can be performed at temperatures from 0 °C to 37 °C. Organ metabolism depends on oxygen to produce adenosine triphosphate and temperatures below 37 °C reduce the metabolic rate and oxygen requirements. The transport and delivery of oxygen in machine perfusion are key determinants in preserving organ viability and cellular function. Oxygen delivery is more challenging than carbon dioxide removal, and oxygenation of the perfusion fluid is temperature dependent. The maximal oxygen content of water-based solutions is inversely related to the temperature, while cellular oxygen demand correlates positively with temperature. Machine perfusion above 20 °C will therefore require an oxygen carrier to enable sufficient oxygen delivery to the liver. Human red blood cells are the most physiological oxygen carriers. Alternative artificial oxygen transporters are hemoglobin-based oxygen carriers, perfluorocarbons, and an extracellular oxygen carrier derived from a marine invertebrate. We describe the principles of oxygen transport, delivery, and consumption in machine perfusion for donor livers using different oxygen carrier-based perfusion solutions and we discuss the properties, advantages, and disadvantages of these carriers and their use. [ABSTRACT FROM AUTHOR]

Published
2021
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42. Hypothermic Machine Perfusion in Liver Transplantation - A Randomized Trial.

Author

Rijn, Rianne van, Schurink, Ivo J., Vries, Yvonne de, van den Berg, Aad P., Cerisuelo, Miriam Cortes, Murad, Sarwa Darwish, Erdmann, Joris I., Gilbo, Nicholas, de Haas, Robbert J., Heaton, Nigel, Hoek, Bart van, Huurman, Volkert A. L., Jochmans, Ina, van Leeuwen, Otto B., de Meijer, Vincent E., Monbaliu, Diethard, Polak, Wojciech G., Slangen, Jules J. G., Troisi, Roberto I., and Vanlander, Aude

Subjects
*LIVER transplantation, *PERFUSION, *COLD storage, *MACHINERY, *CONFIDENCE intervals, *RESEARCH, *STENOSIS, *RESEARCH methodology, *MEDICAL cooperation, *EVALUATION research, *PRESERVATION of organs, tissues, etc., *COMPARATIVE studies, *BILIARY tract, *RESEARCH funding, *REPERFUSION injury, *COLD (Temperature)
Abstract

Background: Transplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited.Methods: In this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). The primary end point was the incidence of nonanastomotic biliary strictures within 6 months after transplantation. Secondary end points included other graft-related and general complications.Results: A total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial). Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group (risk ratio, 0.36; 95% confidence interval [CI], 0.14 to 0.94; P = 0.03). Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group (risk ratio, 0.43; 95% CI, 0.20 to 0.91). Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers (risk ratio, 0.61; 95% CI, 0.39 to 0.96). The cumulative number of treatments for nonanastomotic biliary strictures was lower by a factor of almost 4 after machine perfusion, as compared with control. The incidence of adverse events was similar in the two groups.Conclusions: Hypothermic oxygenated machine perfusion led to a lower risk of nonanastomotic biliary strictures following the transplantation of livers obtained from donors after circulatory death than conventional static cold storage. (Funded by Fonds NutsOhra; DHOPE-DCD ClinicalTrials.gov number, NCT02584283.). [ABSTRACT FROM AUTHOR]

Published
2021
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43. [Viability testing of discarded donor livers; More livers fit for transplantation because of machine perfusion].

Author

van Leeuwen OB, Brüggenwirth IMA, Haring MPD, Lantinga VA, de Meijer VE, and Porte RJ

Subjects
Humans, Netherlands, Organ Preservation instrumentation, Perfusion instrumentation, Liver surgery, Liver Transplantation methods, Organ Preservation methods, Perfusion methods, Tissue Donors, Tissue and Organ Procurement methods
Abstract

In the Netherlands, the average quality of donor organs continues to decrease as a result of the increasing life expectancy, as well as higher incidence of obesity, diabetes mellitus, and other comorbidities in the general population. Storing donor organs on ice, the current standard practice, appears to be inadequate for preserving these high-risk donor livers. Consequently, an increasing number of donor organs is discarded for transplantation. Over the past years, a novel dynamic preservation technique using a machine perfusion device has been developed. Preservation by machine perfusion enables optimisation and viability testing of high-risk donor livers prior to liver transplantation. A large proportion of initially declined donor livers appeared to be suitable for transplantation after evaluation during machine perfusion. Testing of donor livers has led to a significant increase in the number of liver transplantations performed in the Netherlands. This technique has the potential for use in other organs, such as kidney allografts.

Published
2021

45. Selected liver grafts from donation after circulatory death can be safely used for retransplantation - a multicenter retrospective study.

Author

van Reeven M, van Leeuwen OB, van der Helm D, Darwish Murad S, van den Berg AP, van Hoek B, Alwayn IPJ, Polak WG, and Porte RJ

Subjects
Brain Death, Death, Graft Survival, Humans, Liver, Netherlands, Reoperation, Retrospective Studies, Tissue Donors, Tissue and Organ Procurement
Abstract

Due to the growing number of liver transplantations (LTs), there is an increasing number of patients requiring retransplantation (reLT). Data on the use of grafts from extended criteria donors (ECD), especially donation after circulatory death (DCD), for reLT are lacking. We aimed to assess the outcome of patients undergoing reLT using a DCD graft in the Netherlands between 2001 and July 2018. Propensity score matching was used to match each DCD-reLT with three DBD-reLT cases. Primary outcomes were patient and graft survival. Secondary outcome was the incidence of biliary complications, especially nonanastomotic strictures (NAS). 21 DCD-reLT were compared with 63 matched DBD-reLTs. Donors in the DCD-reLT group had a significantly lower BMI (22.4 vs. 24.7 kg/m 2 , P-value = 0.02). Comparison of recipient demographics and ischemia times yielded no significant differences. Patient and graft survival rates were comparable between the two groups. However, the occurrence of nonanastomotic strictures after DCD-reLT was significantly higher (38.1% vs. 12.7%, P-value = 0.02). ReLT with DCD grafts does not result in inferior patient and graft survival compared with DBD grafts in selected patients. Therefore, DCD liver grafts should not routinely be declined for patients awaiting reLT., (© 2020 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

Published
2020
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46. First report of successful transplantation of a pediatric donor liver graft after hypothermic machine perfusion.

Author

Werner MJM, van Leeuwen OB, de Jong IEM, Bodewes FAJA, Fujiyoshi M, Luhker OC, Scheenstra R, de Vries Y, de Kleine RHJ, and Porte RJ

Subjects
Adolescent, Alanine Transaminase metabolism, Aspartate Aminotransferases metabolism, Cholestasis, Intrahepatic surgery, Female, Graft Survival, Humans, Liver Transplantation methods, Oxygen metabolism, Pediatrics, Postoperative Period, Prothrombin Time, Tissue and Organ Procurement methods, Treatment Outcome, Liver surgery, Liver Transplantation instrumentation, Organ Preservation instrumentation, Organ Preservation methods, Perfusion
Abstract

One of the main limiting factors in pediatric liver transplantation is donor availability. For adults, DCD liver grafts are increasingly used to expand the donor pool. To improve outcome after DCD liver transplantation, ex situ machine perfusion is used as an alternative organ preservation strategy, with the supplemental value of providing oxygen to the graft during preservation. We here report the first successful transplantation of a pediatric DCD liver graft after hypothermic oxygenated machine perfusion. The full-size liver graft was derived from a 13-year-old, female DCD donor and was end-ischemic pretreated with dual hypothermic oxygenated machine perfusion. Arterial and portal pressures were set at 18 and 4 mm Hg, slightly lower than protocolized settings for adult livers. During 2 hours of machine perfusion, portal and arterial flows increased from 100 to 210 mL/min and 30 to 63 mL/min, respectively. The pretreated liver graft was implanted in a 16-year-old girl with progressive familial intrahepatic cholestasis type 2. Postoperative AST, ALT, and prothrombin time normalized within a week. The recipient quickly recovered and was discharged from the hospital after 18 days. One year after transplantation, she is in excellent condition with a completely normal liver function and histology. This case is the first report of successful transplantation of a pediatric DCD liver graft after hypothermic oxygenated machine perfusion and illustrates the potential role of ex situ machine perfusion in expanding the donor pool and improving outcome after pediatric liver transplantation., (© 2019 The Authors. Pediatric Transplantation Published by Wiley Periodicals, Inc.)

Published
2019
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