Prolonged preservation by hypothermic machine perfusion facilitates logistics in liver transplantation: A European observational cohort study

Brüggenwirth, Isabel M A; Mueller, Matteo; Lantinga, Veerle A; Camagni, Stefania; Carlis, Riccardo De; Carlis, Luciano De; Colledan, M.; Dondossola, Daniele; Drefs, Moritz; Eden, Janina; Ghinolfi, Davide; Koliogiannis, Dionysios; Lurje, Georg; Manzia, Tommaso Maria; Monbaliu, Diethard; Muiesan, Paolo; Patrono, Damiano; Pratschke, Johann; Romagnoli, Renato; Rayar, Michel; Roma, Francesca; Schlegel, Andrea; Dutkowski, Philipp; Porte, Robert J.; Meijer, Vincent E de

doi:10.1111/ajt.17037

Cited by 58 publications

(48 citation statements)

References 44 publications

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“…A recent multicentre study has collected outcomes of 93 human liver transplants (50 DCD, 43 DBD) with a prolonged HOPE treatment of >4hrs and a median overall preservation of 10hrs. Outcomes were excellent and comparable to other series reported with shorter endischemic HOPE (94). Of note, prolonged HOPE of >4hrs was also shown after more than 10hrs of cold storage in extended criteria donor livers in Germany and in combination with high MELD recipients in Brasil (95).…”

Section: The Role Of Organ Perfusion Techniques For Immune Modulationsupporting

confidence: 83%

Impact of Machine Perfusion on the Immune Response After Liver Transplantation – A Primary Treatment or Just a Delivery Tool

et al. 2022

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The frequent use of marginal livers forces transplant centres to explore novel technologies to improve organ quality and outcomes after implantation. Organ perfusion techniques are therefore frequently discussed with an ever-increasing number of experimental and clinical studies. Two main approaches, hypothermic and normothermic perfusion, are the leading strategies to be introduced in clinical practice in many western countries today. Despite this success, the number of studies, which provide robust data on the underlying mechanisms of protection conveyed through this technology remains scarce, particularly in context of different stages of ischemia-reperfusion-injury (IRI). Prior to a successful clinical implementation of machine perfusion, the concept of IRI and potential key molecules, which should be addressed to reduce IRI-associated inflammation, requires a better exploration. During ischemia, Krebs cycle metabolites, including succinate play a crucial role with their direct impact on the production of reactive oxygen species (ROS) at mitochondrial complex I upon reperfusion. Such features are even more pronounced under normothermic conditions and lead to even higher levels of downstream inflammation. The direct consequence appears with an activation of the innate immune system. The number of articles, which focus on the impact of machine perfusion with and without the use of specific perfusate additives to modulate the inflammatory cascade after transplantation is very small. This review describes first, the subcellular processes found in mitochondria, which instigate the IRI cascade together with proinflammatory downstream effects and their link to the innate immune system. Next, the impact of currently established machine perfusion strategies is described with a focus on protective mechanisms known for the different perfusion approaches. Finally, the role of such dynamic preservation techniques to deliver specific agents, which appear currently of interest to modulate this posttransplant inflammation, is discussed together with future aspects in this field.

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Section: The Role Of Organ Perfusion Techniques For Immune Modulationsupporting

confidence: 83%

Impact of Machine Perfusion on the Immune Response After Liver Transplantation – A Primary Treatment or Just a Delivery Tool

et al. 2022

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“…We encountered two such cases in our study in which HOPE allowed to optimize preservation of the pediatric split graft by prolonging perfusion until the recipient hepatectomy was completed. [31,32] Second, we would like to highlight several important technical points of the proposed standardized HOPE-Split procedure. [13] In contrast to the first report by Spada et al [12] on using dual-HOPE through both the hepatic artery and the portal vein, we advocate single portal perfusion as performed in several ongoing randomized clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Liver transplantation of partial grafts after ex situ splitting during hypothermic oxygenated perfusion—The HOPE–Split pilot study

Rossignol

Muller

Hervieu

et al. 2022

Liver Transplantation

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Partial liver grafts from ex situ splitting are considered marginal due to prolonged static cold storage. The use of ex situ hypothermic oxygenated perfusion (HOPE) may offer a strategy to improve preservation of ex situ split grafts. In this single‐center pilot study, we prospectively performed ex situ liver splitting during HOPE (HOPE–Split) for adult and pediatric partial grafts over a 1‐year period (November 1, 2020 to December 1, 2021). The primary safety endpoint was based on the number of liver graft–related adverse events (LGRAEs) per recipient, including primary nonfunction, biliary complications, hepatic vascular complications, and early relaparotomies and was compared with consecutive single‐center standard ex situ split transplantations (Static–Split) performed from 2018 to 2020. Secondary endpoints included preservation characteristics and early outcomes. Sixteen consecutive HOPE–Split liver transplantations (8 HOPE–Split procedures) were included and compared with 24 Static–Splits. All HOPE–Split grafts were successfully transplanted, and no graft loss nor recipient death was encountered during the median follow‐up of 7.5 months (interquartile range, 5.5–12.5). Mean LGRAE per recipient was similar in both groups (0.31 ± 0.60 vs. 0.46 ± 0.83; p = 0.78) and split duration was not significantly increased for HOPE–Split (216 vs. 180 min; p = 0.45). HOPE–Split grafts underwent perfusion for a median of 125 min, which significantly shortened static cold storage (472 vs. 544 min; p = 0.001), whereas it prolonged total ex vivo preservation (595 vs. 544 min; p = 0.007) and reduced neutrophil infiltration on reperfusion biopsies (p = 0.04) compared with Static–Split. This clinical pilot study presents first feasibility and safety data for transplantation of partial liver grafts undergoing ex situ split during HOPE and suggests improved preservation compared with static ex situ splitting. These preliminary results will allow to set up large‐scale trials on the use of machine perfusion in pediatric and split‐liver transplantation.

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“…Additional evidence comes from three RCTs, which confirmed the HOPE effect, with protection from post-transplant biliary complications, EAD, high peak transaminases, and better graft survival rates in various graft types, including DCD livers [ 119 , 120 , 121 ]. While further studies on the optimal perfusion timing and duration are ongoing, recent evidence from Europe demonstrates the safe facilitation of transplantation logistics and a prolonged preservation period with cold perfusion [ 122 ].…”

Section: Strategies With the Potential To Reduce Cancer Recurrencementioning

confidence: 99%

Mitochondria and Cancer Recurrence after Liver Transplantation—What Is the Benefit of Machine Perfusion?

Parente

Carvalho

Eden

et al. 2022

IJMS

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Tumor recurrence after liver transplantation has been linked to multiple factors, including the recipient’s tumor burden, donor factors, and ischemia-reperfusion injury (IRI). The increasing number of livers accepted from extended criteria donors has forced the transplant community to push the development of dynamic perfusion strategies. The reason behind this progress is the urgent need to reduce the clinical consequences of IRI. Two concepts appear most beneficial and include either the avoidance of ischemia, e.g., the replacement of cold storage by machine perfusion, or secondly, an endischemic organ improvement through perfusion in the recipient center prior to implantation. While several concepts, including normothermic perfusion, were found to reduce recipient transaminase levels and early allograft dysfunction, hypothermic oxygenated perfusion also reduced IRI-associated post-transplant complications and costs. With the impact on mitochondrial injury and subsequent less IRI-inflammation, this endischemic perfusion was also found to reduce the recurrence of hepatocellular carcinoma after liver transplantation. Firstly, this article highlights the contributing factors to tumor recurrence, including the surgical and medical tissue trauma and underlying mechanisms of IRI-associated inflammation. Secondly, it focuses on the role of mitochondria and associated interventions to reduce cancer recurrence. Finally, the role of machine perfusion technology as a delivery tool and as an individual treatment is discussed together with the currently available clinical studies.

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Prolonged preservation by hypothermic machine perfusion facilitates logistics in liver transplantation: A European observational cohort study

Cited by 58 publications

References 44 publications

Impact of Machine Perfusion on the Immune Response After Liver Transplantation – A Primary Treatment or Just a Delivery Tool

Impact of Machine Perfusion on the Immune Response After Liver Transplantation – A Primary Treatment or Just a Delivery Tool

Liver transplantation of partial grafts after ex situ splitting during hypothermic oxygenated perfusion—The HOPE–Split pilot study

Mitochondria and Cancer Recurrence after Liver Transplantation—What Is the Benefit of Machine Perfusion?

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