A multicenter randomized-controlled trial of hypothermic oxygenated perfusion (HOPE) for human liver grafts before transplantation

Schlegel, Andrea; Mueller, Matteo; Muller, Xavier; Eden, Janina; Panconesi, Rebecca; Felten, Stefanie von; Steigmiller, Klaus; Silva, Richard X. Sousa Da; Rougemont, Olivier de; Mabrut, Jean‐Yves; Lesurtel, Mickaël; Cerisuelo, Miriam Cortés; Heaton, Nigel; Allard, Marc Antoine; Adam, René; Monbaliu, Diethard; Jochmans, Ina; Haring, Martijn P D; Porte, Robert J.; Parente, Alessandro; Muiesan, Paolo; Kron, Philipp; Attia, Magdy; Kollmann, Dagmar; Berlakovich, Gabriela; Rogiers, Xavier; Petterson, Karin; Kranich, Anne L.; Amberg, Stefanie; Müllhaupt, Beat; Clavien, Pierre‐Alain; Dutkowski, Philipp

doi:10.1016/j.jhep.2022.12.030

Cited by 69 publications

(101 citation statements)

References 26 publications

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“…Interestingly, the HOPE approach delivering high-perfusate oxygen levels under cold conditions was found to reprogram mitochondria and to prevent later IRI-associated inflammation after liver implantation. Various mechanistic and clinical studies exist together with four randomized controlled trials [ 62 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ]. Based on the underlying mechanism of protection, this perfusion technique reduces posttransplant complications, improves graft survival and reduces re-transplantation rates [ 76 , 82 ].…”

Section: Discussionmentioning

confidence: 99%

“…Various mechanistic and clinical studies exist together with four randomized controlled trials [ 62 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ]. Based on the underlying mechanism of protection, this perfusion technique reduces posttransplant complications, improves graft survival and reduces re-transplantation rates [ 76 , 82 ]. The concept of improved peripheral sinusoidal flow and microvascular protection through the HOPE concept is also interesting [ 83 , 84 ].…”

Section: Discussionmentioning

confidence: 99%

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Association between Hepatocellular Carcinoma Recurrence and Graft Size in Living Donor Liver Transplantation: A Systematic Review

Parente

Cho

Kim

et al. 2023

IJMS

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The aim of this work was to assess the association between graft-to-recipient weight ratio (GRWR) in adult-to-adult living donor liver transplantation (LDLT) and hepatocellular carcinoma (HCC) recurrence. A search of the MEDLINE and EMBASE databases was performed until December 2022 for studies comparing different GRWRs in the prognosis of HCC recipients in LDLT. Data were pooled to evaluate 1- and 3-year survival rates. We identified three studies, including a total of 782 patients (168 GRWR < 0.8 vs. 614 GRWR ≥ 0.8%). The pooled overall survival was 85% and 77% at one year and 90% and 83% at three years for GRWR < 0.8 and GRWR ≥ 0.8, respectively. The largest series found that, in patients within Milan criteria, the GRWR was not associated with lower oncological outcomes. However, patients with HCC outside the Milan criteria with a GRWR < 0.8% had lower survival and higher tumor recurrence rates. The GRWR < 0.8% appears to be associated with lower survival rates in HCC recipients, particularly for candidates with tumors outside established HCC criteria. Although the data are scarce, the results of this study suggest that considering the individual GRWR not only as risk factor for small-for-size-syndrome but also as contributor to HCC recurrence in patients undergoing LDLT would be beneficial. Novel perfusion technologies and pharmacological interventions may contribute to improving outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Association between Hepatocellular Carcinoma Recurrence and Graft Size in Living Donor Liver Transplantation: A Systematic Review

Parente

Cho

Kim

et al. 2023

IJMS

Self Cite

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“…Exploratory findings suggest that HOPE decreases the risk of severe liver graft-related events (fewer severe liver graft-related complications and a lower risk of liver-related graft loss) within a 12-month period after liver transplantation. The HOPE approach can be applied easily after organ transport during recipient hepatectomy [ 40 ]. Additionally, extracellular vesicles (EV) derived from mesenchymal stromal cells delivered during HOPE can be considered a new organ preservation strategy for increasing the donor pool and improving the transplant outcome because the gluconeogenesis system in HOPE+EV group was preserved [ 41 ].…”

Section: Cross Tolerancementioning

confidence: 99%

Ischemic Tolerance—A Way to Reduce the Extent of Ischemia–Reperfusion Damage

Burda

Bürda

Morochovič

2023

Cells

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Individual tissues have significantly different resistance to ischemia–reperfusion damage. There is still no adequate treatment for the consequences of ischemia–reperfusion damage. By utilizing ischemic tolerance, it is possible to achieve a significant reduction in the extent of the cell damage due to ischemia–reperfusion injury. Since ischemia–reperfusion damage usually occurs unexpectedly, the use of preconditioning is extremely limited. In contrast, postconditioning has wider possibilities for use in practice. In both cases, the activation of ischemic tolerance can also be achieved by the application of sublethal stress on a remote organ. Despite very encouraging and successful results in animal experiments, the clinical results have been disappointing so far. To avoid the factors that prevent the activation of ischemic tolerance, the solution has been to use blood plasma containing tolerance effectors. This plasma is taken from healthy donors in which, after exposure to two sublethal stresses within 48 h, effectors of ischemic tolerance occur in the plasma. Application of this activated plasma to recipient animals after the end of lethal ischemia prevents cell death and significantly reduces the consequences of ischemia–reperfusion damage. Until there is a clear chemical identification of the end products of ischemic tolerance, the simplest way of enhancing ischemic tolerance will be the preparation of activated plasma from young healthy donors with the possibility of its immediate use in recipients during the initial treatment.

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“…While the HMP concept was introduced first in the United States (US), centres in Europe have started to use this technology to perfuse high-risk human livers in 2012 using highly oxygenated perfusates. The protective effect of this Hypothermic Oxygenated Perfusion (HOPE) on posttransplant outcomes was described in many retrospective clinical studies and randomized controlled trials (RCTs) in various solid organs [10][11][12][13]. Available studies showed a reduction of early allograft dysfunction (EAD) and recipient complications (e.g., biliary complications for livers and acute rejection for kidneys), better graft survival and lower retransplantation rates after liver and kidney transplantation [10][11][12]14,15].…”

Section: Introductionmentioning

confidence: 99%

“…The protective effect of this Hypothermic Oxygenated Perfusion (HOPE) on posttransplant outcomes was described in many retrospective clinical studies and randomized controlled trials (RCTs) in various solid organs [10][11][12][13]. Available studies showed a reduction of early allograft dysfunction (EAD) and recipient complications (e.g., biliary complications for livers and acute rejection for kidneys), better graft survival and lower retransplantation rates after liver and kidney transplantation [10][11][12]14,15]. The underlying mechanism of the HOPE-technique is based on mitochondrial protection with the reestablishment of an aerobe cellular respiration, previously interrupted during warm and cold ischemia.…”

Section: Introductionmentioning

confidence: 99%

Machine Perfusion of the Pancreas: What Can We Learn from five Decades of Experimental Studies?

2023

J Surg

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Background: Pancreas transplantation is currently the best option for patients with severe complications of diabetes. This organ is however particularly vulnerable to Ischemia-Reperfusion-Injury (IRI) and the transplant procedure is associated with a high risk for recipient complications. It is therefore surprising, that testing and routine use of dynamic preservation strategies is lacking behind other solid organs.Methods: This study includes first, a literature review on the evolution of cold and warm pancreas machine perfusion strategies. Second, pressure-controlled hypothermic oxygenated perfusion (HOPE, pO 2 >60kPa) with fluoresceine is performed in porcine pancreases. Results:No single human pancreas transplant study with machine perfusion is available. A few older animal studies exist with prolonged Hypothermic Machine Perfusion (HMP), with however high perfusion pressures and a lack of active perfusate oxygenation. Tissue oedema and inflammation were the direct consequences. Only recently, such HMP-conditions were adapted, providing an actively oxygenated perfusate at lower perfusion pressures and shorter durations. Such HOPEtreatment was found superior to cold storage and normothermic perfusion in early experimental studies. In our series, HOPE achieved a complete pancreas perfusion, as confirmed by fluorescence despite lower perfusion pressures. Conclusion:HMP with active perfusate oxygenation may achieve similar protective effects in pancreases as seen with livers and kidneys. Lower perfusion pressures appear sufficient to distribute the required oxygen for mitochondrial reprogramming to reduce posttransplant IRI. Prospective clinical studies are planned to test the HOPE-technique in human pancreas transplantation.

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A multicenter randomized-controlled trial of hypothermic oxygenated perfusion (HOPE) for human liver grafts before transplantation

Cited by 69 publications

References 26 publications

Association between Hepatocellular Carcinoma Recurrence and Graft Size in Living Donor Liver Transplantation: A Systematic Review

Association between Hepatocellular Carcinoma Recurrence and Graft Size in Living Donor Liver Transplantation: A Systematic Review

Ischemic Tolerance—A Way to Reduce the Extent of Ischemia–Reperfusion Damage

Machine Perfusion of the Pancreas: What Can We Learn from five Decades of Experimental Studies?

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