Hypothermic Machine Perfusion in Liver Transplantation - A Randomized Trial

Rianne van Rijn; Ivo J Schurink; Yvonne de Vries; Aad P van den Berg; Miriam Cortes Cerisuelo; Sarwa Darwish Murad; Joris I Erdmann; Nicholas Gilbo; Robbert J de Haas; Nigel Heaton; Bart van Hoek; Volkert A L Huurman; Ina Jochmans; Otto B van Leeuwen; Vincent E de Meijer; Diethard Monbaliu; Wojciech G Polak; Jules J G Slangen; Roberto I Troisi; Aude Vanlander; Jeroen de Jonge; Robert J Porte; DHOPE-DCD Trial Investigators

doi:10.1056/NEJMoa2031532

Hypothermic Machine Perfusion in Liver Transplantation - A Randomized Trial

N Engl J Med. 2021 Apr 15;384(15):1391-1401. doi: 10.1056/NEJMoa2031532. Epub 2021 Feb 24.

Authors

Rianne van Rijn¹, Ivo J Schurink¹, Yvonne de Vries¹, Aad P van den Berg¹, Miriam Cortes Cerisuelo¹, Sarwa Darwish Murad¹, Joris I Erdmann¹, Nicholas Gilbo¹, Robbert J de Haas¹, Nigel Heaton¹, Bart van Hoek¹, Volkert A L Huurman¹, Ina Jochmans¹, Otto B van Leeuwen¹, Vincent E de Meijer¹, Diethard Monbaliu¹, Wojciech G Polak¹, Jules J G Slangen¹, Roberto I Troisi¹, Aude Vanlander¹, Jeroen de Jonge¹, Robert J Porte¹; DHOPE-DCD Trial Investigators

Collaborators

DHOPE-DCD Trial Investigators:
Robert J Porte, Rianne van Rijn, Yvonne de Vries, Otto B van Leeuwen, Martijn P D Haring, Jeroen de Jonge, Aad P van den Berg, Bart van Hoek, Eric A M Verschuuren, Mostafa El Moumni, Cyril Moers, Liza Lahaye, Jan Bottema, Robbert J de Haas, Jules J G Slangen, François E J A Willemssen, Marieke de Boer, Ruben de Kleine, Carlijn Buis, Vincent de Meijer, Joost Klaase, Maarten Nijkamp, Frederik Hoogwater, Alix Matton, Laura Burlage, Gert-Jan Pelgrim, Leonie Venema, Rinse Ubbink, Wojciech Polak, Sarwa Darwish Murad, Jan IJzermans, Herold Metselaar, Ivo Schurink, Sjoerd van den Hoek, Nemo Backx, Dimitri Sneiders, Özgür Eryigit, Stef Luimes, Femke de Goeij, Joris Erdmann, Volkert Huurman, Ian Alwayn, Babs de Klerk, Jason Doppenberg, Asel Arykbaeva, Lex Habets, Fenna van de Leemkolk, Diethard Monbaliu, Ina Jochmans, Nicholas Gilbo, Jacques Pirenne, Maurico Sainz-Barriga, Sarah Mertens, Linde Besard, Sofie Vets, Karlien Degezelle, Lieven Lenaerts, Kristof Van de Voorde, Frederik Gaublomme, Roberto Troisi, Aude Vanlander, Xavier Rogiers, Kathleen Segers, Betsy van Loo, Nigel Heaton, Miriam Cortes Cerisuelo, Melissa Preziosi, Anastazja Mroz, Vernie Ramalingham, Jo Gambell, Ane Zamalloa, Mona Dave, Augustine Joseph, Merve Surucu

Affiliation

¹ From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium.

PMID: 33626248
DOI: 10.1056/NEJMoa2031532

Abstract

Background: Transplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited.

Methods: In this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). The primary end point was the incidence of nonanastomotic biliary strictures within 6 months after transplantation. Secondary end points included other graft-related and general complications.

Results: A total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial). Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group (risk ratio, 0.36; 95% confidence interval [CI], 0.14 to 0.94; P = 0.03). Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group (risk ratio, 0.43; 95% CI, 0.20 to 0.91). Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers (risk ratio, 0.61; 95% CI, 0.39 to 0.96). The cumulative number of treatments for nonanastomotic biliary strictures was lower by a factor of almost 4 after machine perfusion, as compared with control. The incidence of adverse events was similar in the two groups.

Conclusions: Hypothermic oxygenated machine perfusion led to a lower risk of nonanastomotic biliary strictures following the transplantation of livers obtained from donors after circulatory death than conventional static cold storage. (Funded by Fonds NutsOhra; DHOPE-DCD ClinicalTrials.gov number, NCT02584283.).

Publication types

Comparative Study
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Biliary Tract / pathology*
Cold Ischemia*
Cold Temperature
Constriction, Pathologic / prevention & control
Female
Humans
Liver Transplantation*
Male
Middle Aged
Organ Preservation / methods*
Perfusion
Reperfusion Injury / prevention & control

Associated data

ClinicalTrials.gov/NCT02584283

Grants and funding

1404-012/Fonds NutsOhra