Liver splitting during normothermic machine perfusion: a novel method to combine the advantages of both in-situ and ex-vivo techniques

Lau, Ngee-Soon; Ly, Mark; Dennis, Claude; Ewenson, Kasper; Ly, Hayden; Huang, Joanna Lou; Cabanes‐Creus, Marti; Chanda, Sumon; Wang, Chuanmin; Lisowski, Leszek; Liu, Ken; Kench, James G.; McCaughan, Geoffrey W.; Crawford, Michael; Pulitano, Carlo

doi:10.1016/j.hpb.2023.02.003

Cited by 13 publications

(17 citation statements)

References 12 publications

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“…All livers were split and then perfused according to our protocol for long-term perfusion using a modified commercial perfusion machine as previously described. 6,10,11 In brief, perfusion was achieved using a commercial system (Liver assist, Xvivo, Groningen, the Netherlands) that was modified for the purpose of long-term perfusion by addition of long-term oxygenators (Quadrox-iD Pediatric, Macquet, Getinge Group, Rastatt, Germany), a gas blender (Low Flow 2003 Series, Bio-Med Devices, CT), and a dialysis filter (Prismaflex or Polyflux, Baxter Healthcare, IL) (Figure 1A).…”

Section: Liver Perfusionmentioning

confidence: 99%

“…The impact of bile spillage and extended handling of the liver may become more important as techniques for liver splitting during machine perfusion are developed to improve split liver transplantation. [6][7][8][9][10] Furthermore, microbial contamination of perfusate during the long-term perfusion of human livers in the range of days-to-weeks has not been described and could be a limiting factor on the use of these organs for transplantation.…”

Section: Introductionmentioning

confidence: 99%

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Microbial Contamination During Long-term Ex Vivo Normothermic Machine Perfusion of Human Livers

Lau

Dennis

et al. 2023

Transplantation

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Background. Normothermic machine perfusion permits the ex vivo preservation of human livers before transplantation. Long-term perfusion for days-to-weeks provides the opportunity for enhanced pretransplant assessment and potential regeneration of organs. However, this risks microbial contamination and infection of the recipient if the organ is transplanted. An understanding of perfusate microbial contamination is required to inform infection control procedures and antimicrobial prophylaxis for this technology. Methods. We modified a liver perfusion machine for long-term use by adding long-term oxygenators and a dialysis filter. Human livers that were not suitable for transplantation were perfused using a red-cell-based perfusate under aseptic and normothermic conditions (36 °C) with a goal of 14 d. Cephazolin was added to the perfusate for antimicrobial prophylaxis. Perfusate and bile were sampled every 72 h for microbial culture. Results. Eighteen partial human livers (9 left lateral segment grafts and 9 extended right grafts) were perfused using our perfusion system. The median survival was 7.2 d. All organs surviving longer than 7 d (9/18) had negative perfusate cultures at 24 and 48 h. Half of the grafts (9/18) became culture-positive by the end of perfusion. Microbial contaminants included Gram-negative (Pseudomonas species, Proteus mirabilis, Stenotrophomonas maltophilia) and Gram-positive bacteria (Staphylococcus epidermidis, Enterococcus faecalis, and Bacillus species) as well as yeast (Candida albicans). Conclusions. Microbial contamination of perfusate is common during long-term perfusion of human livers with both exogenous and endogenous sources. Enhanced infection control practices and review of targeted antimicrobial prophylaxis are likely to be necessary for translation into the clinical arena.

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Section: Liver Perfusionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Microbial Contamination During Long-term Ex Vivo Normothermic Machine Perfusion of Human Livers

Lau

Dennis

et al. 2023

Transplantation

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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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Long-term ex situ normothermic machine perfusion allows regeneration of human livers with severe bile duct injury

Ly,

Lau,

Dennis

et al. 2024

American Journal of Transplantation

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Liver splitting during normothermic machine perfusion: a novel method to combine the advantages of both in-situ and ex-vivo techniques

Cited by 13 publications

References 12 publications

Microbial Contamination During Long-term Ex Vivo Normothermic Machine Perfusion of Human Livers

Microbial Contamination During Long-term Ex Vivo Normothermic Machine Perfusion of Human Livers

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

Long-term ex situ normothermic machine perfusion allows regeneration of human livers with severe bile duct injury

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