The role of normothermic machine perfusion in liver transplantation

Martins, Paulo N.; Buchwald, Julianna; Mergental, Hynek; Vargas, Luciano; Quintini, Cristiano

doi:10.1016/j.ijsu.2020.05.026

Cited by 30 publications

(29 citation statements)

References 44 publications

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“…Many physicians envision a future where MP is used to improve the function of each donor liver to achieve maximal graft utilization and minimize discard rates [ 10 , 11 ], and one potential method to improve graft function is targeting metabolism. While numerous studies have demonstrated potential metabolic targets in the liver, renal, and intestinal IRI response [ 12 , 13 , 14 , 15 , 16 ], few studies have examined the metabolic changes that occur in the human liver during transplantation [ 12 , 17 , 18 , 19 , 20 ] and fewer still during ex situ machine perfusion [ 4 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Tryptophan Metabolism via the Kynurenine Pathway: Implications for Graft Optimization during Machine Perfusion

Zhang

Carroll

Raigani

et al. 2020

JCM

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Access to liver transplantation continues to be hindered by the severe organ shortage. Extended-criteria donor livers could be used to expand the donor pool but are prone to ischemia-reperfusion injury (IRI) and post-transplant graft dysfunction. Ex situ machine perfusion may be used as a platform to rehabilitate discarded or extended-criteria livers prior to transplantation, though there is a lack of data guiding the utilization of different perfusion modalities and therapeutics. Since amino acid derivatives involved in inflammatory and antioxidant pathways are critical in IRI, we analyzed differences in amino acid metabolism in seven discarded non-steatotic human livers during normothermic- (NMP) and subnormothermic-machine perfusion (SNMP) using data from untargeted metabolomic profiling. We found notable differences in tryptophan, histamine, and glutathione metabolism. Greater tryptophan metabolism via the kynurenine pathway during NMP was indicated by significantly higher kynurenine and kynurenate tissue concentrations compared to pre-perfusion levels. Livers undergoing SNMP demonstrated impaired glutathione synthesis indicated by depletion of reduced and oxidized glutathione tissue concentrations. Notably, ATP and energy charge ratios were greater in livers during SNMP compared to NMP. Given these findings, several targeted therapeutic interventions are proposed to mitigate IRI during liver machine perfusion and optimize marginal liver grafts during SNMP and NMP.

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Section: Introductionmentioning

confidence: 99%

Tryptophan Metabolism via the Kynurenine Pathway: Implications for Graft Optimization during Machine Perfusion

Zhang

Carroll

Raigani

et al. 2020

JCM

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“…NMP has been successfully used to resuscitate ECD or marginal livers, prolong the liver preservation time, and reduce IRI-related complications (11,20,21). The cold ischemia time can be reduced using NMP, while graft ischemia still cannot be fully avoided during the conventional procedure of organ procurement, preparation, and implantation (22).…”

Section: Discussionmentioning

confidence: 99%

A marginal liver graft with hyperbilirubinemia transplanted successfully by ischemia-free liver transplantation

Huang¹,

Chen²,

Wang³

et al. 2021

Ann Transl Med

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The shortage of transplant organs remains a serious issue worldwide, and using liver grafts from extended criteria donors could expand the donor pool. Extended criteria donor liver allografts have a high chance of complications such as primary nonfunction, early allograft dysfunction, and ischemictype biliary lesions. How to employ these extended criteria donors safely and effectively warrants further investigation. Herein, we report the successful use of a marginal donor liver with hyperbilirubinemia to save the life of an acute-on-chronic liver failure recipient using a new surgical technique: ischemia-free liver transplantation (IFLT). The graft was retrieved for transplantation due to the following reasons: (I) the recipient was in a life-threatening situation and no living donor donation candidate was available; (II) the graft was considered transplantable except for cholestasis; and (III) IFLT could reduce ischemia/reperfusion injury (IRI), resuscitate the allograft ex situ, and maintain organ viability before transplantation. The graft was transplanted successfully using the IFLT procedure. Although anatomic biliary stricture occurred after surgery, no IRI-related complications were found during the follow-up. The use of liver grafts from extended criteria donors is safe and effective under IFLT. Additional IFLT clinical studies need to be performed, particularly concerning donor management, graft selection, and ex situ resuscitation.

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“…A machine used to preserve donor organs under physiological conditions outside the body mimics an in vivo situation and maintains full metabolic organ function. Especially for ECD organs, NMP may be ideal to cautiously bridge time to implantation since it allows for in-depth organ quality assessment [ 28 ]. The first in man renal transplantation after NMP was described in 2011 by the group around Hosgood and Nicholson [ 29 ].…”

Section: Bridging Time To Transplantation—from Static Cold Storage To Machine Perfusionmentioning

confidence: 99%

Ex Vivo Mesenchymal Stem Cell Therapy to Regenerate Machine Perfused Organs

Bogensperger

Hofmann

Messner

et al. 2021

IJMS

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Transplantation represents the treatment of choice for many end-stage diseases but is limited by the shortage of healthy donor organs. Ex situ normothermic machine perfusion (NMP) has the potential to extend the donor pool by facilitating the use of marginal quality organs such as those from donors after cardiac death (DCD) and extended criteria donors (ECD). NMP provides a platform for organ quality assessment but also offers the opportunity to treat and eventually regenerate organs during the perfusion process prior to transplantation. Due to their anti-inflammatory, immunomodulatory and regenerative capacity, mesenchymal stem cells (MSCs) are considered as an interesting tool in this model system. Only a limited number of studies have reported on the use of MSCs during ex situ machine perfusion so far with a focus on feasibility and safety aspects. At this point, no clinical benefits have been conclusively demonstrated, and studies with controlled transplantation set-ups are urgently warranted to elucidate favorable effects of MSCs in order to improve organs during ex situ machine perfusion.

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The role of normothermic machine perfusion in liver transplantation

Cited by 30 publications

References 44 publications

Tryptophan Metabolism via the Kynurenine Pathway: Implications for Graft Optimization during Machine Perfusion

Tryptophan Metabolism via the Kynurenine Pathway: Implications for Graft Optimization during Machine Perfusion

A marginal liver graft with hyperbilirubinemia transplanted successfully by ischemia-free liver transplantation

Ex Vivo Mesenchymal Stem Cell Therapy to Regenerate Machine Perfused Organs

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