DCN for ECD Livers

Safe Transplantation of Extended Criteria Donor Livers: Two-center Experience With Resuscitation and Viability Assessment of 206 Livers Using Sequential Hypo- and Normothermic Machine Perfusion

The goal of this observational study is to learn whether extended criteria donor livers can be safely transplanted after sequential hypo- and normothermic machine perfusion in recipients requiring a liver transplant for end-stage liver disease, including a long-term follow-up. The main questions it aims to answer are:

• Death censored graft-survival
• Overall patient survival
• Frequency of frequent post-transplant complications (e.g. non-anastomotic biliary strictures)

Study Overview

• Status: Completed
• Conditions: Liver Transplantation
• Intervention / Treatment: Procedure: DHOPE-COR-NMP

Detailed Description

With the increasing shortage of suitable donor livers for transplantation, extended criteria donor (ECD) livers may bridge the gap between available donor organs and donor livers needed. However, these ECD livers are associated with a higher risk of posttransplant complications. With the development of machine perfusion (MP) strategies over the recent years, (dual) hypothermic oxygenated perfusion ((D)HOPE) is established as a safe and effective way to reduce ischemia reperfusion injury. This leads to a decrease in early allograft dysfunction and non-anastomotic biliary strictures (NAS). On the other hand, normothermic machine perfusion (NMP) is mainly used for hepatobiliary functional assessment of liver grafts prior to transplantation. Combining both perfusion techniques through 1 hour of controlled oxygenated rewarming (COR), enables safe selection and transplantation of ECD livers after DHOPE-COR-NMP. Long-term outcomes are now available from two centers.

• Study Type: Observational
• Enrollment (Actual): 143

Contacts and Locations

Study Locations

• Netherlands
  • Provincie Groningen
    • Groningen, Provincie Groningen, Netherlands, 9713GZ
      • University Medical Center Groningen
  • South Holland
    • Rotterdam, South Holland, Netherlands, 3015GD
      • Erasmus Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients (>18 years) undergoing liver transplantation of extended criteria donor livers, which therefore required resuscitation and viability assessment through the previously published DHOPE-COR-NMP protocol based on a blood-based perfusate.

Description

Inclusion Criteria:

• Adult patients (>18 years old)
• Donor livers that required resuscitation and viability assessment through the previously published sequential hypo- and normothermic liver machine perfusion (DHOPE-COR-NMP) protocol based on a blood-based perfusate.

Exclusion Criteria:

• Multiorgan transplantation
• Split liver transplant
• Living donor liver transplantation
• Previous donor organ perfusion (e.g. Normothermic Regional Perfusion)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; Adult patients (>18 years) who underwent liver transplantation of donor livers that required resuscitation and viability assessment through the previously published protocol for sequential hypo- and normothermic liver machine perfusion with controlled oxygenated rewarming (DHOPE-COR-NMP) based on a blood-based perfusate.	Procedure: DHOPE-COR-NMP; Resuscitation and viability assessment through the previously published protocol of sequential hypo- and normothermic liver machine perfusion with controlled oxygenated rewarming (DHOPE-COR-NMP) based on a blood-based perfusate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death-censored graft survival	Time from liver transplantation until re-transplantation or death due to graft dysfunction, with censoring of subjects who died with a functioning graft.	1 year post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall patient survival	Time from liver transplantation until all-cause death	1 year post-transplant
• Overall graft survival	Time from liver transplantation until re-transplantation or all-cause death.	1 year post-transplant
Number of participants with primary non function	Livers failing to sustain their primary function, leading to death or re-transplantation within 7 days of the primary procedure, in the presence of patent blood supply and outflow (8).	From transplantation until 7 days post-transplant
Occurrence of hepatic arterial thrombosis	Radiologically or surgically proven thrombosis of the hepatic artery.	1 year post-transplant
Occurrence of portal vein thrombosis	Radiologically or surgically proven thrombosis of the portal vein.	1 year post-transplant
Occurrence of venous outflow tract obstruction	Radiologically or surgically proven thrombosis of the main hepatic veins or the inferior vena cava.	1 year post-transplant
Occurrence of non-anastomotic biliary strictures	Any irregularity or narrowing of the lumen of the intrahepatic or extrahepatic donor bile ducts, excluding the biliary anastomosis, diagnosed with the use of cholangiography in combination with clinical symptoms (e.g., jaundice or cholangitis) or an elevation of cholestatic laboratory variables, in the presence of a patent hepatic artery (5).	1 year post-transplant
Occurrence of anastomotic biliary strictures	Strictures occurring at the anastomosis of donor choledochal duct and recipient choledochal duct or jejunal Roux-limb.	1 year post-transplant
Occurrence of biliary leakage	Fluid with an elevated (>3x serum) bilirubin level in the abdominal drain or intra-abdominal fluid on or after post-operative day 3 or the need for radiological intervention (i.e. interventional drainage) owing to biliary collections or re-laparotomy due to biliary peritonitis (9).	From 3 days after transplantation until the the first year post-transplant
Biliary complications: as a composite	A composite of individually studied outcome measures (reported as one single outcome measure), composed of: non-anastomotic biliary strictures, anastomotic biliary strictures and biliary leakage.	1 year post-transplant
Intensive care stay	Intensive care stay post-transplantation	From transplantation until discharge from the Intensive care unit to the ward after transplantation or date of death from any cause during initial admission, whichever came first, assessed up to 6 months
Total hospital stay	Defined as total hospital stay from transplantation until discharge, including intensive care unit stay	From transplantation until discharge after transplantation, or date of death from any cause during initial admission, whichever came first, assessed up to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of post-transplant incidence of biliary interventions	The occurrence and frequency of the composite of one of the following biliary interventions (reported as one single outcome measure): Endoscopic Retrograde Cholangio- and Pancreaticography, drainage performed by percutaneous transhepatic cholangiography and re-interventions for biliary complications (e.g. bile leaks)	Until 6 months after liver transplantation

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: University Medical Center Groningen

Publications and helpful links

General Publications

• van Rijn R, Schurink IJ, de Vries Y, van den Berg AP, Cortes Cerisuelo M, Darwish Murad S, Erdmann JI, Gilbo N, de Haas RJ, Heaton N, van Hoek B, Huurman VAL, Jochmans I, van Leeuwen OB, de Meijer VE, Monbaliu D, Polak WG, Slangen JJG, Troisi RI, Vanlander A, de Jonge J, Porte RJ; DHOPE-DCD Trial Investigators. 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.
• de Vries Y, Berendsen TA, Fujiyoshi M, van den Berg AP, Blokzijl H, de Boer MT, van der Heide F, de Kleine RHJ, van Leeuwen OB, Matton APM, Werner MJM, Lisman T, de Meijer VE, Porte R. Transplantation of high-risk donor livers after resuscitation and viability assessment using a combined protocol of oxygenated hypothermic, rewarming and normothermic machine perfusion: study protocol for a prospective, single-arm study (DHOPE-COR-NMP trial). BMJ Open. 2019 Aug 15;9(8):e028596. doi: 10.1136/bmjopen-2018-028596.
• van Leeuwen OB, de Vries Y, Fujiyoshi M, Nijsten MWN, Ubbink R, Pelgrim GJ, Werner MJM, Reyntjens KMEM, van den Berg AP, de Boer MT, de Kleine RHJ, Lisman T, de Meijer VE, Porte RJ. 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 Nov;270(5):906-914. doi: 10.1097/SLA.0000000000003540.
• Eden J, Bruggenwirth IMA, Berlakovich G, Buchholz BM, Botea F, Camagni S, Cescon M, Cillo U, Colli F, Compagnon P, De Carlis LG, De Carlis R, Di Benedetto F, Dingfelder J, Diogo D, Dondossola D, Drefs M, Fronek J, Germinario G, Gringeri E, Gyori G, Kocik M, Kucukerbil EH, Koliogiannis D, Lam HD, Lurje G, Magistri P, Monbaliu D, Moumni ME, Patrono D, Polak WG, Ravaioli M, Rayar M, Romagnoli R, Sorensen G, Uluk D, Schlegel A, Porte RJ, Dutkowski P, de Meijer VE. Long-term outcomes after hypothermic oxygenated machine perfusion and transplantation of 1,202 donor livers in a real-world setting (HOPE-REAL study). J Hepatol. 2025 Jan;82(1):97-106. doi: 10.1016/j.jhep.2024.06.035. Epub 2024 Jul 3.
• Foley DP, Fernandez LA, Leverson G, Anderson M, Mezrich J, Sollinger HW, D'Alessandro A. Biliary complications after liver transplantation from donation after cardiac death donors: an analysis of risk factors and long-term outcomes from a single center. Ann Surg. 2011 Apr;253(4):817-25. doi: 10.1097/SLA.0b013e3182104784.
• Nemes B, Gaman G, Polak WG, Gelley F, Hara T, Ono S, Baimakhanov Z, Piros L, Eguchi S. Extended-criteria donors in liver transplantation Part II: reviewing the impact of extended-criteria donors on the complications and outcomes of liver transplantation. Expert Rev Gastroenterol Hepatol. 2016 Jul;10(7):841-59. doi: 10.1586/17474124.2016.1149062. Epub 2016 Mar 2.
• Schlegel A, Porte R, Dutkowski P. Protective mechanisms and current clinical evidence of hypothermic oxygenated machine perfusion (HOPE) in preventing post-transplant cholangiopathy. J Hepatol. 2022 Jun;76(6):1330-1347. doi: 10.1016/j.jhep.2022.01.024.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Actual): May 1, 2025
• Study Completion (Actual): October 31, 2025

Study Registration Dates

• First Submitted: January 13, 2025
• First Submitted That Met QC Criteria: January 27, 2025
• First Posted (Actual): February 3, 2025

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Liver Transplantation; Machine Perfusion; Extended Criteria Donors
• Other Study ID Numbers: MEC-2024-0738

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No