Hypothermic Oxygenated Machine Perfusion Reduces Early Allograft Injury and Improves Post-transplant Outcomes in Extended Criteria Donation Liver Transplantation From Donation After Brain Death: Results From a Multicenter Randomized Controlled Trial (HOPE ECD-DBD)

Zoltan Czigany¹, Johann Pratschke², Jiří Froněk³, Markus Guba⁴, Wenzel Schöning^{1

2}, Dimitri Aristotle Raptis^{5

6}, Joachim Andrassy⁴, Matthijs Kramer⁷, Pavel Strnad⁸, Rene Hany Tolba⁹, Wenjia Liu¹, Theresa Keller¹⁰, Hannah Miller¹, Sandra Pavicevic², Deniz Uluk², Matej Kocik³, Isabella Lurje¹¹, Christian Trautwein⁸, Arianeb Mehrabi¹², Irinel Popescu¹³, Florian Wolfgang Rudolf Vondran¹⁴, Cynthia Ju¹⁵, Frank Tacke^{8

11}, Ulf Peter Neumann¹, Georg Lurje^{1

2}

Affiliations

¹ Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
² Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Germany.
³ Department of Transplantation Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
⁴ Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany.
⁵ Department of HPB Surgery and Liver Transplantation, Royal Free Hospital, London, UK.
⁶ University College London, London, UK.
⁷ Department of Hepatology, Maastricht University Medical Center (MUMC), Maastricht, The Netherlands.
⁸ Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
⁹ Institute for Laboratory Animal Science and Experimental Surgery, University Hospital RWTH Aachen, Aachen, Germany.
¹⁰ Institute for Biometry and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
¹¹ Department of Hepatology and Gastroenterology, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Germany.
¹² Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Germany.
¹³ Department of General Surgery and Liver transplantation, Fundeni Clinical Institute, Bucharest, Romania.
¹⁴ Department for General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany.
¹⁵ Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX.

PMID: 34334635
DOI: 10.1097/SLA.0000000000005110

Randomized Controlled Trial

Hypothermic Oxygenated Machine Perfusion Reduces Early Allograft Injury and Improves Post-transplant Outcomes in Extended Criteria Donation Liver Transplantation From Donation After Brain Death: Results From a Multicenter Randomized Controlled Trial (HOPE ECD-DBD)

Zoltan Czigany et al. Ann Surg. 2021.

. 2021 Nov 1;274(5):705-712.

doi: 10.1097/SLA.0000000000005110.

Authors

Affiliations

¹ Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
² Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Germany.
³ Department of Transplantation Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
⁴ Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany.
⁵ Department of HPB Surgery and Liver Transplantation, Royal Free Hospital, London, UK.
⁶ University College London, London, UK.
⁷ Department of Hepatology, Maastricht University Medical Center (MUMC), Maastricht, The Netherlands.
⁸ Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
⁹ Institute for Laboratory Animal Science and Experimental Surgery, University Hospital RWTH Aachen, Aachen, Germany.
¹⁰ Institute for Biometry and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
¹¹ Department of Hepatology and Gastroenterology, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Germany.
¹² Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Germany.
¹³ Department of General Surgery and Liver transplantation, Fundeni Clinical Institute, Bucharest, Romania.
¹⁴ Department for General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany.
¹⁵ Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX.

PMID: 34334635
DOI: 10.1097/SLA.0000000000005110

Abstract

Objective: The aim of this study was to evaluate peak serum alanine aminotransferase (ALT) and postoperative clinical outcomes after hypothermic oxygenated machine perfusion (HOPE) versus static cold storage (SCS) in extended criteria donation (ECD) liver transplantation (LT) from donation after brain death (DBD).

Background: HOPE might improve outcomes in LT, particularly in high-risk settings such as ECD organs after DBD, but this hypothesis has not yet been tested in a randomized controlled clinical trial (RCT).

Methods: Between September 2017 and September 2020, 46 patients undergoing ECD-DBD LT from four centers were randomly assigned to HOPE (n = 23) or SCS (n = 23). Peak-ALT levels within 7 days following LT constituted the primary endpoint. Secondary endpoints included incidence of postoperative complications [Clavien-Dindo classification (CD), Comprehensive Complication Index (CCI)], length of intensive care- (ICU) and hospital-stay, and incidence of early allograft dysfunction (EAD).

Results: Demographics were equally distributed between both groups [donor age: 72 (IQR: 59-78) years, recipient age: 62 (IQR: 55-65) years, labMELD: 15 (IQR: 9-25), 38 male and 8 female recipients]. HOPE resulted in a 47% decrease in serum peak ALT [418 (IQR: 221-828) vs 796 (IQR: 477-1195) IU/L, P = 0.030], a significant reduction in 90-day complications [44% vs 74% CD grade ≥3, P = 0.036; 32 (IQR: 12-56) vs 52 (IQR: 35-98) CCI, P = 0.021], and shorter ICU- and hospital-stays [5 (IQR: 4-8) vs 8 (IQR: 5-18) days, P = 0.045; 20 (IQR: 16-27) vs 36 (IQR: 23-62) days, P = 0.002] compared to SCS. A trend toward reduced EAD was observed for HOPE (17% vs 35%; P = 0.314).

Conclusion: This multicenter RCT demonstrates that HOPE, in comparison to SCS, significantly reduces early allograft injury and improves post-transplant outcomes in ECD-DBD liver transplantation.

Trial registration: ClinicalTrials.gov NCT03124641.

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Conflict of interest statement

The authors report no conflicts of interest.

References

1. Czigany Z, Lurje I, Tolba RH, et al. Machine perfusion for liver transplantation in the era of marginal organs—new kids on the block. Liver Int 2019; 39:228–249.
1. Nasralla D, Coussios CC, Mergental H, et al. A randomized trial of normothermic preservation in liver transplantation. Nature 2018; 557:50–56.
1. van Leeuwen OB, de Vries Y, Fujiyoshi M, et al. Transplantation of high-risk donor livers after ex situ resuscitation and assessment using combined hypo- and normothermic machine perfusion: a prospective clinical trial. Ann Surg 2019; 270:906–914.
1. Schlegel A, de Rougemont O, Graf R, et al. Protective mechanisms of end-ischemic cold machine perfusion in DCD liver grafts. J Hepatol 2013; 58:278–286.
1. Patrono D, Surra A, Catalano G, et al. Hypothermic oxygenated machine perfusion of liver grafts from brain-dead donors. Sci Rep 2019; 9:9337.

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Hypothermic Oxygenated Machine Perfusion Reduces Early Allograft Injury and Improves Post-transplant Outcomes in Extended Criteria Donation Liver Transplantation From Donation After Brain Death: Results From a Multicenter Randomized Controlled Trial (HOPE ECD-DBD)

Affiliations

Hypothermic Oxygenated Machine Perfusion Reduces Early Allograft Injury and Improves Post-transplant Outcomes in Extended Criteria Donation Liver Transplantation From Donation After Brain Death: Results From a Multicenter Randomized Controlled Trial (HOPE ECD-DBD)

Authors

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Abstract

Conflict of interest statement

References

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MeSH terms

Associated data

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Full Text Sources