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5. Liver transplantation for non-resectable colorectal liver metastases: the International Hepato-Pancreato-Biliary Association consensus guidelines

Author

Bonney, Glenn K, Chew, Claire Alexandra, Lodge, Peter, Hubbard, Joleen, Halazun, Karim J, Trunecka, Pavel, Muiesan, Paolo, Mirza, Darius F, Isaac, John, Laing, Richard W, Iyer, Shridhar Ganpathi, Chee, Cheng Ean, Yong, Wei Peng, Muthiah, Mark Dhinesh, Panaro, Fabrizio, Sanabria, Juan, Grothey, Axel, Moodley, Keymanthri, Chau, Ian, Chan, Albert C Y, Wang, Chih Chi, Menon, Krishna, Sapisochin, Gonzalo, Hagness, Morten, Dueland, Svein, Line, Pål-Dag, and Adam, René

Published
2021
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6. Discarded livers tested by normothermic machine perfusion in the VITTAL trial: Secondary end points and 5-year outcomes

Author

Mergental, Hynek, primary, Laing, Richard W., additional, Kirkham, Amanda J., additional, Clarke, George, additional, Boteon, Yuri L., additional, Barton, Darren, additional, Neil, Desley A.H., additional, Isaac, John R., additional, Roberts, Keith J., additional, Abradelo, Manuel, additional, Schlegel, Andrea, additional, Dasari, Bobby V.M., additional, Ferguson, James W., additional, Cilliers, Hentie, additional, Morris, Chris, additional, Friend, Peter J., additional, Yap, Christina, additional, Afford, Simon C., additional, Perera, M. Thamara P.R., additional, and Mirza, Darius F., additional

Published
2023
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11. Transplantation of discarded livers following viability testing with normothermic machine perfusion

Author

Mergental, Hynek, Laing, Richard W., Kirkham, Amanda J., Perera, M. Thamara P. R., Boteon, Yuri L., Attard, Joseph, Barton, Darren, Curbishley, Stuart, Wilkhu, Manpreet, Neil, Desley A. H., Hübscher, Stefan G., Muiesan, Paolo, Isaac, John R., Roberts, Keith J., Abradelo, Manuel, Schlegel, Andrea, Ferguson, James, Cilliers, Hentie, Bion, Julian, Adams, David H., Morris, Chris, Friend, Peter J., Yap, Christina, Afford, Simon C., and Mirza, Darius F.

Published
2020
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13. Preoperative C-Reactive Protein-to-Albumin Ratio and Its Ability to Predict Outcomes of Pancreatic Cancer Resection: A Systematic Review

Author

Hajibandeh, Shahin, primary, Hajibandeh, Shahab, additional, Romman, Saleh, additional, Parente, Alessandro, additional, Laing, Richard W., additional, Satyadas, Thomas, additional, Subar, Daren, additional, Aroori, Somaiah, additional, Bhatt, Anand, additional, Durkin, Damien, additional, Athwal, Tejinderjit S., additional, and Roberts, Keith J., additional

Published
2023
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14. Discarded livers tested by normothermic machine perfusion in the VITTAL trial: Secondary end points and 5-year outcomes.

Author

Mergental, Hynek, Laing, Richard W., Kirkham, Amanda J., Clarke, George, Boteon, Yuri L., Barton, Darren, Neil, Desley A. H., Isaac, John R., Roberts, Keith J., Abradelo, Manuel, Schlegel, Andrea, Dasari, Bobby V. M., Ferguson, James W., Cilliers, Hentie, Morris, Chris, Friend, Peter J., Yap, Christina, Afford, Simon C., Perera, M. Thamara P. R., and Mirza, Darius F.

Published
2024
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15. In situ normothermic regional perfusion versus ex situ normothermic machine perfusion in liver transplantation from donation after circulatory death

Author

Mohkam, Kayvan, Nasralla, David, Mergental, Hynek, Muller, Xavier, Butler, Andrew, Jassem, Wayel, Imber, Charles, Monbaliu, Diethard, Perera, M Thamara PR, Laing, Richard W, García-Valdecasas, Juan Carlos, Paul, Andreas, Dondero, Federica, Cauchy, François, Savier, Eric, Scatton, Olivier, Robin, Fabien, Sulpice, Laurent, Bucur, Petru, Salamé, Ephrem, Pittau, Gabriella, Allard, Marc-Antoine, Pradat, Pierre, Rossignol, Guillaume, Mabrut, Jean-Yves, Ploeg, Rutger J, Friend, Peter J, Mirza, Darius F, Lesurtel, Mickaël, Consortium For Organ Preservation In Europe (COPE), Mohkam, Kayvan [0000-0002-9695-0902], Mergental, Hynek [0000-0001-5480-9380], Muller, Xavier [0000-0002-8849-5495], Savier, Eric [0000-0003-4131-2222], Rossignol, Guillaume [0000-0002-9896-4144], Mabrut, Jean-Yves [0000-0002-5701-3588], Lesurtel, Mickaël [0000-0003-2397-4599], and Apollo - University of Cambridge Repository

Subjects
End Stage Liver Disease, Perfusion, Carcinoma, Hepatocellular, Graft Survival, Liver Neoplasms, Humans, Aspartate Aminotransferases, Organ Preservation, Severity of Illness Index, Liver Transplantation
Abstract

In situ normothermic regional perfusion (NRP) and ex situ normothermic machine perfusion (NMP) aim to improve the outcomes of liver transplantation (LT) using controlled donation after circulatory death (cDCD). NRP and NMP have not yet been compared directly. In this international observational study, outcomes of LT performed between 2015 and 2019 for organs procured from cDCD donors subjected to NRP or NMP commenced at the donor center were compared using propensity score matching (PSM). Of the 224 cDCD donations in the NRP cohort that proceeded to asystole, 193 livers were procured, resulting in 157 transplants. In the NMP cohort, perfusion was commenced in all 40 cases and resulted in 34 transplants (use rates: 70% vs. 85% [p = 0.052], respectively). After PSM, 34 NMP liver recipients were matched with 68 NRP liver recipients. The two cohorts were similar for donor functional warm ischemia time (21 min after NRP vs. 20 min after NMP; p = 0.17), UK-Donation After Circulatory Death risk score (5 vs. 5 points; p = 0.38), and laboratory Model for End-Stage Liver Disease scores (12 vs. 12 points; p = 0.83). The incidence of nonanastomotic biliary strictures (1.5% vs. 2.9%; p > 0.99), early allograft dysfunction (20.6% vs. 8.8%; p = 0.13), and 30-day graft loss (4.4% vs. 8.8%; p = 0.40) were similar, although peak posttransplant aspartate aminotransferase levels were higher in the NRP cohort (872 vs. 344 IU/L; p < 0.001). NRP livers were more frequently allocated to recipients suffering from hepatocellular carcinoma (HCC; 60.3% vs. 20.6%; p < 0.001). HCC-censored 2-year graft and patient survival rates were 91.5% versus 88.2% (p = 0.52) and 97.9% versus 94.1% (p = 0.25) after NRP and NMP, respectively. Both perfusion techniques achieved similar outcomes and appeared to match benchmarks expected for donation after brain death livers. This study may inform the design of a definitive trial.

Published
2022

17. Introduction of the Concept of Diagnostic Sensitivity and Specificity of Normothermic Perfusion Protocols to Assess High‐Risk Donor Livers

Author

Mergental, Hynek, primary, Laing, Richard W., additional, Hodson, James, additional, Boteon, Yuri L., additional, Attard, Joseph A., additional, Walace, Laine L., additional, Neil, Desley A. H., additional, Barton, Darren, additional, Schlegel, Andrea, additional, Muiesan, Paolo, additional, Abradelo, Manuel, additional, Isaac, John R., additional, Roberts, Keith, additional, Perera, M. Thamara P. R., additional, Afford, Simon C., additional, and Mirza, Darius F., additional

Published
2021
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21. The Delivery of Multipotent Adult Progenitor Cells to Extended Criteria Human Donor Livers Using Normothermic Machine Perfusion

Author

Laing, Richard W., primary, Stubblefield, Samantha, additional, Wallace, Lorraine, additional, Roobrouck, Valerie D., additional, Bhogal, Ricky H., additional, Schlegel, Andrea, additional, Boteon, Yuri L., additional, Reynolds, Gary M., additional, Ting, Anthony E., additional, Mirza, Darius F., additional, Newsome, Philip N., additional, Mergental, Hynek, additional, and Afford, Simon C., additional

Published
2020
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22. Correction: The impact on the bioenergetic status and oxidative-mediated tissue injury of a combined protocol of hypothermic and normothermic machine perfusion using an acellular haemoglobin-based oxygen carrier: The cold-to-warm machine perfusion of the liver

Author

Boteon, Yuri L., primary, Laing, Richard W., additional, Schlegel, Andrea, additional, Wallace, Lorraine, additional, Smith, Amanda, additional, Attard, Joseph, additional, Bhogal, Ricky H., additional, Reynolds, Gary, additional, Thamara PR Perera, M., additional, Muiesan, Paolo, additional, Mirza, Darius F., additional, Mergental, Hynek, additional, and Afford, Simon C., additional

Published
2020
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23. The impact on the bioenergetic status and oxidative-mediated tissue injury of a combined protocol of hypothermic and normothermic machine perfusion using an acellular haemoglobin-based oxygen carrier: The cold-to-warm machine perfusion of the liver

Author

Boteon, Yuri L., primary, Laing, Richard W., additional, Schlegel, Andrea, additional, Wallace, Lorraine, additional, Smith, Amanda, additional, Attard, Joseph, additional, Bhogal, Ricky H., additional, Reynolds, Gary, additional, PR Perera, M. Thamara, additional, Muiesan, Paolo, additional, Mirza, Darius F., additional, Mergental, Hynek, additional, and Afford, Simon C., additional

Published
2019
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24. Combined Hypothermic and Normothermic Machine Perfusion Improves Functional Recovery of Extended Criteria Donor Livers

Author

Boteon, Yuri L., primary, Laing, Richard W., additional, Schlegel, Andrea, additional, Wallace, Lorraine, additional, Smith, Amanda, additional, Attard, Joseph, additional, Bhogal, Ricky H., additional, Neil, Desley A. H., additional, Hübscher, Stefan, additional, Perera, M. Thamara P. R., additional, Mirza, Darius F., additional, Afford, Simon C., additional, and Mergental, Hynek, additional

Published
2018
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25. Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, non-randomised, prospective, single-arm trial

Author

Laing, Richard W, Mergental, Hynek, Yap, Christina, Kirkham, Amanda, Whilku, Manpreet, Barton, Darren, Curbishley, Stuart, Boteon, Yuri L, Neil, Desley A, Hübscher, Stefan G, Perera, M Thamara P R, Muiesan, Paolo, Isaac, John, Roberts, Keith J, Cilliers, Hentie, Afford, Simon C, and Mirza, Darius F

Subjects
Tissue Survival, Time Factors, Tissue and Organ Procurement, Non-Randomized Controlled Trials as Topic, Organ Preservation, hepatobiliary tumours, hepatobiliary disease, Transplant Recipients, Liver Transplantation, Perfusion, Liver, transplant surgery, hepatology, Practice Guidelines as Topic, Protocol, Feasibility Studies, Humans, Surgery, Prospective Studies
Abstract

Introduction The use of marginal or extended criteria donor livers is increasing. These organs carry a greater risk of initial dysfunction and early failure, as well as inferior long-term outcomes. As such, many are rejected due to a perceived risk of use and use varies widely between centres. Ex situ normothermic machine perfusion of the liver (NMP-L) may enable the safe transplantation of organs that meet defined objective criteria denoting their high-risk status and are currently being declined for use by all the UK transplant centres. Methods and analysis Viability testing and transplantation of marginal livers is an open-label, non-randomised, prospective, single-arm trial designed to determine whether currently unused donor livers can be salvaged and safely transplanted with equivalent outcomes in terms of patient survival. The procured rejected livers must meet predefined criteria that objectively denote their marginal condition. The liver is subjected to NMP-L following a period of static cold storage. Organs metabolising lactate to ≤2.5 mmol/L within 4 hours of the perfusion commencing in combination with two or more of the following parameters—bile production, metabolism of glucose, a hepatic arterial flow rate ≥150 mL/min and a portal venous flow rate ≥500 mL/min, a pH ≥7.30 and/or maintain a homogeneous perfusion—will be considered viable and transplanted into a suitable consented recipient. The coprimary outcome measures are the success rate of NMP-L to produce a transplantable organ and 90-day patient post-transplant survival. Ethics and dissemination The protocol was approved by the National Research Ethics Service (London—Dulwich Research Ethics Committee, 16/LO/1056), the Medicines and Healthcare Products Regulatory Agency and is endorsed by the National Health Service Blood and Transplant Research, Innovation and Novel Technologies Advisory Group. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications. Trial registration number NCT02740608; Pre-results.

Published
2017

26. Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High‐Risk Livers Using Normothermic Machine Perfusion

Author

Mergental, Hynek, primary, Stephenson, Barnaby T. F., additional, Laing, Richard W., additional, Kirkham, Amanda J., additional, Neil, Desley A. H., additional, Wallace, Lorraine L., additional, Boteon, Yuri L., additional, Widmer, Jeannette, additional, Bhogal, Ricky H., additional, Perera, M. Thamara P. R., additional, Smith, Amanda, additional, Reynolds, Gary M., additional, Yap, Christina, additional, Hübscher, Stefan G., additional, Mirza, Darius F., additional, and Afford, Simon C., additional

Published
2018
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31. Is Hepatocyte Necrosis a Good Marker of Donor Liver Viability During Machine Perfusion?

Author

Neil, Desley A.H., Mergental, Hynek, Hann, Angus, Laing, Richard W, Hartog, Hermien, Mirza, Darius F, and Perera, M. Thamara P.R.

Subjects
LIVER, PERFUSION, NECROSIS, MACHINERY
Abstract

They use histological assessment of hepatocyte necrosis as the basis of determining whether a liver is nonviable and conclude that lactate clearance during NMP is not able to differentiate between viable and nonviable livers. In conclusion, significant hepatocyte necrosis in DBD grafts can be successfully transplanted following NMP, indicating that hepatocyte necrosis I per se i is not a reliable surrogate for viability of a donor liver. [Extracted from the article]

Published
2022
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32. In situ normothermic regional perfusion versus ex situ normothermic machine perfusion in liver transplantation from donation after circulatory death.

Author

Mohkam K, Nasralla D, Mergental H, Muller X, Butler A, Jassem W, Imber C, Monbaliu D, Perera MTPR, Laing RW, García-Valdecasas JC, Paul A, Dondero F, Cauchy F, Savier E, Scatton O, Robin F, Sulpice L, Bucur P, Salamé E, Pittau G, Allard MA, Pradat P, Rossignol G, Mabrut JY, Ploeg RJ, Friend PJ, Mirza DF, and Lesurtel M

Subjects
Aspartate Aminotransferases, Graft Survival, Humans, Organ Preservation methods, Perfusion methods, Severity of Illness Index, Carcinoma, Hepatocellular, End Stage Liver Disease surgery, Liver Neoplasms, Liver Transplantation methods
Abstract

In situ normothermic regional perfusion (NRP) and ex situ normothermic machine perfusion (NMP) aim to improve the outcomes of liver transplantation (LT) using controlled donation after circulatory death (cDCD). NRP and NMP have not yet been compared directly. In this international observational study, outcomes of LT performed between 2015 and 2019 for organs procured from cDCD donors subjected to NRP or NMP commenced at the donor center were compared using propensity score matching (PSM). Of the 224 cDCD donations in the NRP cohort that proceeded to asystole, 193 livers were procured, resulting in 157 transplants. In the NMP cohort, perfusion was commenced in all 40 cases and resulted in 34 transplants (use rates: 70% vs. 85% [p = 0.052], respectively). After PSM, 34 NMP liver recipients were matched with 68 NRP liver recipients. The two cohorts were similar for donor functional warm ischemia time (21 min after NRP vs. 20 min after NMP; p = 0.17), UK-Donation After Circulatory Death risk score (5 vs. 5 points; p = 0.38), and laboratory Model for End-Stage Liver Disease scores (12 vs. 12 points; p = 0.83). The incidence of nonanastomotic biliary strictures (1.5% vs. 2.9%; p > 0.99), early allograft dysfunction (20.6% vs. 8.8%; p = 0.13), and 30-day graft loss (4.4% vs. 8.8%; p = 0.40) were similar, although peak posttransplant aspartate aminotransferase levels were higher in the NRP cohort (872 vs. 344 IU/L; p < 0.001). NRP livers were more frequently allocated to recipients suffering from hepatocellular carcinoma (HCC; 60.3% vs. 20.6%; p < 0.001). HCC-censored 2-year graft and patient survival rates were 91.5% versus 88.2% (p = 0.52) and 97.9% versus 94.1% (p = 0.25) after NRP and NMP, respectively. Both perfusion techniques achieved similar outcomes and appeared to match benchmarks expected for donation after brain death livers. This study may inform the design of a definitive trial., (© 2022 The Authors. Liver Transplantation published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Published
2022
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