Prolonged Ex Vivo Normothermic Perfusion of a Split Liver

Lau, Ngee-Soon; Ly, Mark; Jacques, Andrew; Ewenson, Kasper; Mestrovic, Nicole; Almoflihi, Abdullah; Koutalistras, N.; Liu, Ken; Kench, James G.; McCaughan, Geoffrey W.; Crawford, Michael; Pulitano, Carlo

doi:10.1097/txd.0000000000001216

Cited by 19 publications

(20 citation statements)

References 5 publications

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“…Although livers considered for split procedures are highly selected, they can nonetheless suffer from the consequences of surgical manipulation and prolonged cold ischemia time and might benefit from an enhanced preservation modality. Liver splitting during NMP is technically feasible 86 and recently, prolonged NMP preservation of a split liver graft has been recently reported 87 . Ideally, the liver could be placed on the NMP device at the donor hospital, transported and split while on the device at the first recipient hospital, and then transported under continuous NMP at the second recipient hospital, an approach that would combine better preservation with the optimization of human resources.…”

Section: Transplant Logisticsmentioning

confidence: 99%

Some Like It Hot. Utility and Mechanisms of Ex-Situ Normothermic Machine Perfusion of the Liver

Patrono

Stefano

Rigo

et al. 2023

EJT

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The need for donor pool expansion in liver transplantation has increased utilization of grafts from so-called extended-criteria donors. Machine perfusion technology can improve preservation of these grafts, and its use has been associated with improved short-and long-term outcomes. During normothermic machine perfusion the graft is preserved at 37°C, and continuously supplied with oxygen and nutrients. The main advantages of this preservation technique are the reduction of ischemia-reperfusion injury, the prolongation of preservation time, and the possibility to assess graft viability or delivering therapies ex-vivo. However, it is still considered as a complex technique, which has elicited some reticence about its utilization among transplant professionals. The aim of this narrative review is to give a synthetic but comprehensive update on normothermic machine perfusion in liver transplantation, discussing its fundamental principles and clinical implications. Technical and procedural aspects, along with physiological bases, will be discussed. Results of clinical trials will be summarized, including those highlighting the role of this technology in the delicate process of assessing liver viability and its impact on transplant logistics. Finally, latest findings in the field of basic and translational research on organ reconditioning will be reported.

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Section: Transplant Logisticsmentioning

confidence: 99%

Some Like It Hot. Utility and Mechanisms of Ex-Situ Normothermic Machine Perfusion of the Liver

Patrono

Stefano

Rigo

et al. 2023

EJT

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“…The liver was split ex-vivo with continuous dual perfusion using the technique we have previously described. [9][10][11] In brief, the liver was divided into a left lateral segment graft (LLSG, segments 2 and 3) and an extended right graft (ERG, segments 1 and 4-8). The coeliac trunk was allocated to the LLSG, and the main portal vein was kept with the ERG.…”

Section: Perfusion Protocolmentioning

confidence: 99%

“…We modi ed a commercial liver perfusion system (Liver assist, Xvivo, Gronigen, Netherlands) as previously described using commercially-available equipment. [9][10][11] This system utilises a dual-pump con guration with an open venous reservoir and thermoregulatory unit. The modi cations are summarised in Fig.…”

Section: Modi Ed Perfusion Machinementioning

confidence: 99%

“…Long-term ex-vivo perfusion of human livers using normothermic conditions also represents a unique opportunity for studying living human tissue ex-vivo. By splitting whole human livers during normothermic machine perfusion as we have previously described, [9][10][11] this technology can be applied to two partial grafts. This could provide a simulated environment for the testing of therapeutics with a matched control, and the study liver injury and regeneration.…”

Section: Introductionmentioning

confidence: 99%

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Long-term ex-vivo normothermic perfusion of human split livers: a unique model to study new therapeutics and increase the number of available organs

Lau¹,

Ly²,

Dennis³

et al. 2023

Preprint

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Current perfusion technology only allows livers to be preserved ex-vivo for short periods. Long-term normothermic perfusion of livers is an emerging field with tremendous potential for the assessment, recovery, and modification of organs. In this study, we aimed develop a long-term model of ex-vivo perfusion including a surgical split and simultaneous perfusion of both partial grafts. Our long-term perfusion system included long-term oxygenators, a gas-mixer and a dialysis filter. Human livers declined for transplantation were perfused using a red-cell based perfusate under normothermic conditions (36°C) and then split and simultaneously perfused on separate machines. Ten human livers were split resulting in 20 partial grafts. The median ex-vivo survival was 165 hours (7 days). Long-term graft survival was demonstrated by lactate clearance, bile production, Factor-V production, and storage of adenosine triphosphate. The grafts that survived > 7 days demonstrated significantly higher bile production, Factor-V production, and hepatic arterial flow and significantly lower microvesicular steatosis. We report reliable long-term ex-vivo perfusion of human livers and demonstrate the ability to split and perfuse these organs using a reproducible protocol. This provides the opportunity for improved assessment of organs and could act as a model for the testing of therapeutics with a matched control.

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“…In an effort to increase the availability of transplantable human liver grafts, split-liver perfusion of the left and right hepatic lobes has also been reported [ 4 ]. Schreiter et al described a human ex vivo model for acetaminophen-induced liver injury [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Development of a Novel Ex Vivo Porcine Hepatic Segmental Perfusion Proof-of-Concept Model Towards More Ethical Translational Research

Kanani¹,

Isherwood²,

ElSamani³

et al. 2023

Cureus

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IntroductionEx vivo machine perfusion describes the technique where organs are continuously perfused and oxygenated extracorporeally (at physiological conditions) to maintain the organs' viability. To our knowledge, there are currently no reported studies describing ex vivo perfusion of a single hepatic segment. Here, we describe the development of a porcine ex vivo hepatic segmental perfusion model to demonstrate proof of concept and support further research into the ex vivo perfusion of the human liver using discarded tissue. MethodsWhole livers were retrieved from abattoir-derived pigs and connected to a normothermic extracorporeal perfusion circuit. Constant segmental perfusion via the common or segmental hepatic artery and portal vein with heparinised autologous blood was established. The viability of the perfused organ was assessed by monitoring perfusion pressures, flow rates and histology samples. ResultsFollowing perfusion and optimisation of the model for three hepatic segments, the third perfusion demonstrated viable hepatocytes centrally after 4 h of segmental perfusion. ConclusionEx vivo hepatic segmental perfusion is technically challenging but its success in a porcine model and the principles learned should facilitate the development of an analogous human model using discarded tissue following formal liver resections. The model would use a healthy liver segment following a major formal resection such as a hemi-hepatectomy and ex vivo perfusion performed via a segmental hepatic artery and portal vein. If successful this model would represent a significant development and enable ethical translation research to assess the response of human livers to a variety of stressors, including toxicity and infection.

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Prolonged Ex Vivo Normothermic Perfusion of a Split Liver

Cited by 19 publications

References 5 publications

Some Like It Hot. Utility and Mechanisms of Ex-Situ Normothermic Machine Perfusion of the Liver

Some Like It Hot. Utility and Mechanisms of Ex-Situ Normothermic Machine Perfusion of the Liver

Long-term ex-vivo normothermic perfusion of human split livers: a unique model to study new therapeutics and increase the number of available organs

Development of a Novel Ex Vivo Porcine Hepatic Segmental Perfusion Proof-of-Concept Model Towards More Ethical Translational Research

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