Machine Perfusion of Donor Livers for Transplantation: A Proposal for Standardized Nomenclature and Reporting Guidelines

doi:10.1111/ajt.13843

Review

. 2016 Oct;16(10):2932-2942.

doi: 10.1111/ajt.13843. Epub 2016 Jun 13.

Machine Perfusion of Donor Livers for Transplantation: A Proposal for Standardized Nomenclature and Reporting Guidelines

S A Karangwa^{1

2}, P Dutkowski³, P Fontes^{4

5}, P J Friend⁶, J V Guarrera⁷, J F Markmann⁸, H Mergental⁹, T Minor¹⁰, C Quintini¹¹, M Selzner¹², K Uygun¹³, C J Watson¹⁴, R J Porte¹

Affiliations

¹ Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
² Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
³ Department of Surgery & Transplantation, University Hospital Zurich, Zurich, Switzerland.
⁴ Thomas E. Starzl Transplantation Institute Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA.
⁵ McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA.
⁶ Nuffield Department of Surgery, Oxford Transplant Centre, University of Oxford, Churchill Hospital, Oxford, UK.
⁷ Department of Surgery, Center for Liver Disease and Transplantation, Columbia University Medical Center, New York, NY.
⁸ Transplant Center, Massachusetts General Hospital, Boston, MA.
⁹ Liver Unit, University Hospital Birmingham, Birmingham, UK.
¹⁰ Department of Surgical Research, Clinic for General Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany.
¹¹ Department of Surgery, Transplant Center, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH.
¹² Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
¹³ Department of Surgery, Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
¹⁴ University of Cambridge Department of Surgery and the NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

PMID: 27129409
PMCID: PMC5132023
DOI: 10.1111/ajt.13843

Review

Machine Perfusion of Donor Livers for Transplantation: A Proposal for Standardized Nomenclature and Reporting Guidelines

S A Karangwa et al. Am J Transplant. 2016 Oct.

. 2016 Oct;16(10):2932-2942.

doi: 10.1111/ajt.13843. Epub 2016 Jun 13.

Authors

Affiliations

¹ Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
² Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
³ Department of Surgery & Transplantation, University Hospital Zurich, Zurich, Switzerland.
⁴ Thomas E. Starzl Transplantation Institute Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA.
⁵ McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA.
⁶ Nuffield Department of Surgery, Oxford Transplant Centre, University of Oxford, Churchill Hospital, Oxford, UK.
⁷ Department of Surgery, Center for Liver Disease and Transplantation, Columbia University Medical Center, New York, NY.
⁸ Transplant Center, Massachusetts General Hospital, Boston, MA.
⁹ Liver Unit, University Hospital Birmingham, Birmingham, UK.
¹⁰ Department of Surgical Research, Clinic for General Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany.
¹¹ Department of Surgery, Transplant Center, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH.
¹² Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
¹³ Department of Surgery, Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
¹⁴ University of Cambridge Department of Surgery and the NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

PMID: 27129409
PMCID: PMC5132023
DOI: 10.1111/ajt.13843

Abstract

With increasing demand for donor organs for transplantation, machine perfusion (MP) promises to be a beneficial alternative preservation method for donor livers, particularly those considered to be of suboptimal quality, also known as extended criteria donor livers. Over the last decade, numerous studies researching MP of donor livers have been published and incredible advances have been made in both experimental and clinical research in this area. With numerous research groups working on MP, various techniques are being explored, often applying different nomenclature. The objective of this review is to catalog the differences observed in the nomenclature used in the current literature to denote various MP techniques and the manner in which methodology is reported. From this analysis, we propose a standardization of nomenclature on liver MP to maximize consistency and to enable reliable comparison and meta-analyses of studies. In addition, we propose a standardized set of guidelines for reporting the methodology of future studies on liver MP that will facilitate comparison as well as clinical implementation of liver MP procedures.

Keywords: clinical research/practice; donors and donation: extended criteria; guidelines; liver transplantation/hepatology; organ perfusion and preservation.

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Figures

**Figure 1**
**Flow chart illustrating study selection and inclusion procedure.** Irrelevant titles included studies mainly involving *in vivo* perfusion (and not machine perfusion), *in vitro* cell studies, follow‐up studies on MP or studies involving analysis of data from studies on MP of donor livers without including the MP procedure description in the methodology.

**Figure 2**
**Charts illustrating classification of the timing of machine perfusion.** MP conducted within 3 h of organ procurement and followed by a period of SCS is considered as pre‐SCS MP, whereas that performed after a period of at least 3 h of SCS preservation prior to implantation is considered as post‐SCS MP. Additionally, MP can be performed between periods of SCS. Duration of SCS and preservation MP conducted within the 3 h windows on either end of the procedure remains unspecified and can be widely varied. Lastly, MP can also be performed for the entire preservation period (immediately after organ procurement until just before implantation).

**Figure 3**
**Graphic presentation of the change in the rate of metabolism with decreasing temperature.** Based on Van't Hoff's principle (expressed as $Q_{10} = {(k_{2} / k_{1})}^{10 / (t_{2} - t_{1})}$ ), this graph demonstrates the significantly reduced metabolism at hypothermic temperatures (0°C–12°C). The vertical lines in the graphs indicate the lower endpoint of temperature ranges of the different types of MP proposed. NMP; normothermic machine perfusion (35°C–38°C); SMP, subnormothermic machine perfusion (25°C–34°C); MMP, mid‐thermic machine perfusion (13°C–24°C); HMP, hypothermic machine perfusion (0°C–12°C).

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References

1. Yanaga K, Makowka L, Lebeau G, et al. A new liver perfusion and preservation system for transplantation research in large animals. J Invest Surg 1990; 3: 65–75. - PMC - PubMed
1. Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta‐analysis protocols (PRISMA‐P) 2015 statement. Syst Rev 2015; 4: 1. - PMC - PubMed
1. Berendsen TA, Bruinsma BG, Lee J, et al. A simplified subnormothermic machine perfusion system restores ischemically damaged liver grafts in a rat model of orthotopic liver transplantation. Transplant Res 2012; 1: 6. - PMC - PubMed
1. Berendsen TA, Bruinsma BG, Puts CF, et al. Supercooling enables long‐term transplantation survival following 4 days of liver preservation. Nat Med 2014; 20: 790–793. - PMC - PubMed
1. Boehnert MU, Yeung JC, Bazerbachi F, et al. Normothermic acellular ex vivo liver perfusion reduces liver and bile duct injury of pig livers retrieved after cardiac death. Am J Transplant 2013; 13: 1441–1449. - PubMed

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[1] Yanaga K, Makowka L, Lebeau G, et al. A new liver perfusion and preservation system for transplantation research in large animals. J Invest Surg 1990; 3: 65–75. - PMC - PubMed

[2] Yanaga K, Makowka L, Lebeau G, et al. A new liver perfusion and preservation system for transplantation research in large animals. J Invest Surg 1990; 3: 65–75. - PMC - PubMed

[3] Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta‐analysis protocols (PRISMA‐P) 2015 statement. Syst Rev 2015; 4: 1. - PMC - PubMed

[4] Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta‐analysis protocols (PRISMA‐P) 2015 statement. Syst Rev 2015; 4: 1. - PMC - PubMed

[5] Berendsen TA, Bruinsma BG, Lee J, et al. A simplified subnormothermic machine perfusion system restores ischemically damaged liver grafts in a rat model of orthotopic liver transplantation. Transplant Res 2012; 1: 6. - PMC - PubMed

[6] Berendsen TA, Bruinsma BG, Lee J, et al. A simplified subnormothermic machine perfusion system restores ischemically damaged liver grafts in a rat model of orthotopic liver transplantation. Transplant Res 2012; 1: 6. - PMC - PubMed

[7] Berendsen TA, Bruinsma BG, Puts CF, et al. Supercooling enables long‐term transplantation survival following 4 days of liver preservation. Nat Med 2014; 20: 790–793. - PMC - PubMed

[8] Berendsen TA, Bruinsma BG, Puts CF, et al. Supercooling enables long‐term transplantation survival following 4 days of liver preservation. Nat Med 2014; 20: 790–793. - PMC - PubMed

[9] Boehnert MU, Yeung JC, Bazerbachi F, et al. Normothermic acellular ex vivo liver perfusion reduces liver and bile duct injury of pig livers retrieved after cardiac death. Am J Transplant 2013; 13: 1441–1449. - PubMed

[10] Boehnert MU, Yeung JC, Bazerbachi F, et al. Normothermic acellular ex vivo liver perfusion reduces liver and bile duct injury of pig livers retrieved after cardiac death. Am J Transplant 2013; 13: 1441–1449. - PubMed

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Machine Perfusion of Donor Livers for Transplantation: A Proposal for Standardized Nomenclature and Reporting Guidelines

Affiliations

Machine Perfusion of Donor Livers for Transplantation: A Proposal for Standardized Nomenclature and Reporting Guidelines

Authors

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Abstract

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