Liver Transplantation After ex Vivo Liver Perfusion (EVOLVE)

Liver Transplantation After ex Vivo Liver Perfusion - The EVOLVE Study

Today, it is difficult to predict liver function after transplantation and therefore livers where poor function is assumed (marginal livers) become discarded. The study aim is to increase the number of available donor livers, especially for liver cancer patients, by pre-treating and testing marginal ones (extended criteria donor (ECD) livers) liver on a liver perfusion machine. A liver perfusion machine can simulate liver transplantation and enables functional/quality testing before transplantation. The machine will hopefully also make marginal livers more functional by reducing ischemia- & reperfusion injury. A marginal donor liver is perfused ex situ with oxygenated blood from a blood donor on a machine. The liver can be tested here for function using internationally recognized criteria. At the same time, the investigators will carry out analyzes with microdialysis which can give a better picture of organ function and damage. Additionally, various samples of the liver and perfusate will be collected. Liver that achieves criteria for transplantation will be offered to the recipient.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Metastases; Liver Transplant; Complications; Liver Cancer; Transplant; Transplant; Failure, Liver; Transplant; Complication, Rejection; Transplant Dysfunction
• Intervention / Treatment: Procedure: Liver transplantation

Detailed Description

The study is a single-center, prospective, open-label cohort study designed to determine the efficacy of liver perfusion of marginal ECD livers on a perfusion machine before liver transplantation. Donor livers will be preserved with standard cooling followed by three perfusion modes (Dual hypothermic oxygenated machine perfusion (DHOPE) / Controlled oxygenated rewarming (COR) / Normothermic machine perfusion (NMP)), a method used internationally to pre-treating marginal livers before liver transplantation and which able testing of function and quality before a transplantation is performed. Only livers that fulfill international criteria (Groningen criteria) will be approved for Ltx. In this study microdialysis will be used to monitoring the liver during machine perfusion and up to 14 days in the postoperative course to monitor the function of the liver. The hypothesis is that microdialysis will provide a better prediction of liver function than the existing Groeningen criteria. The investigators expect that most included patients, who receive ECD livers perfused on a machine, will receive a postoperative well-functioning liver graft which entails a significant survival benefit. The study is designed as a cohort study because included patients have a very poor prognosis (median overall survival of approx. 6 months) and others treatment options are lacking. The primary objective is to establish definitive, objective criteria for pre-transplant liver function by defining a threshold value for microdialysis parameters (especially lactate) between donor livers that will restore function and those that will not during ex vivo machine perfusion in ECD livers, which are superior to established criteria (Groeningen and Viability testing and transplantation of marginal livers (VITTAL) criteria)). The primary endpoint is microdialysis lactate level between donor livers after 4 hours of normothermic machine perfusion in ECD livers.

The follow-up period is 12 months.

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Søren E Pischke, MD, PhD; Phone Number: +47 45486579; Email: s.e.pischke@medisin.uio.no

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Signed informed consent
• ≥ 18 years
• Indication for liver transplantation (one criteria must be met):
• Colorectal cancer patients who have received 1st and 2nd line chemotherapy where the treatment has been stopped due to progression or toxicity and the patient is not eligible for SECA-2 (Survival Following Liver Transplantation for Patients With Nonresectable Liver-only Colorectal Metastases) study.
• Hepatocellular carcinoma patients who are not suitable for standard liver transplantation, liver resection or local treatment (Transarterial Chemoembolisation or Selective internal radiotherapy). The patients must have progression or intolerance (toxicity) for immune checkpoint inhibitors or 1st line treatment.
• Cholangiocarcinoma patients who have progression or intolerance to first-line chemotherapy.
• Benign liver disease with urgent need for transplantation within months, but no regular graft is available.
• Life expectancy ≤ 6 months
• Willing, able and expected cooperation to attend follow-up examinations
• Patients who have a need for liver transplantation but cannot participate in other transplant studies or participation in another clinical trial with randomization to liver transplantation.

For malignant disease the following criteria must be met:

• Good performance status assessed at the discretion of the treating physician.
• ECOG (Eastern Cooperative Oncology Group) 0 or 1

• Satisfactory blood tests

  • Hemoglobin >8 g/dl
  • Neutrophiles >1.0 (after any Granulocyte colony-stimulating factor)
  • Platelets >75
  • Bilirubin <1.5 x upper normal level
  • ASAT (Aspartate aminotransferase), ALAT (alanine aminotransferase) <5 x upper normal level
  • Albumin above lower normal level.

Exclusion Criteria:

• Already listed for ordinary Ltx with expectance of getting offered a regular liver graft within a reasonable time-frame.
• Patients included in the control arm of the SECA-3 study or the Excalibur studies except for the Ltx arm of the Excalibur I study.
• Mental conditions rendering the subject incapable to understand the nature, scope, and consequences of the trial.
• Any reason why, in the opinion of the investigator, the patient should not participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Liver transplanted patient; Patients who are transplanted with an ECD liver after pretreatment with a liver perfusion machine	Procedure: Liver transplantation; Patients who receive an ECD liver after an ex-vivo liver perfusion where the liver has been tested for function and approved according to international functional criteria (Groeningen criteria)
No Intervention: Non-liver transplanted patient; Patients who are not offered a liver transplantation during the inclusion period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lactate level in microdialysate from hilar plate after normothermic machine perfusion - 4 hours	Lactate level in microdialysate from hilar plate after normothermic machine perfusion in extended criteria donors livers.	4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lactate level in microdialysate from liver tissue after normothermic machine perfusion - 2.5 hours	Microdialysis lactate level in donor liver tissue after 2.5 hours of normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Lactate level in microdialysate from liver tissue after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours	Microdialysis lactate level in donor liver tissue after 2 hours of Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Pyruvate level in microdialysate from liver tissue after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours	Microdialysis pyruvate level in donor liver tissue after 2 hours of Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Glycerol level in microdialysate from liver tissue after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours	Microdialysis glycerol level in donor liver tissue after 2 hours of Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Glucose level in microdialysate from liver tissue after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours	Microdialysis glucose level in donor liver tissue after 2 hours of Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Lactate level in microdialysate from liver tissue after controlled oxygenated rewarming machine perfusion - 1 hour	Microdialysis lactate level in donor livers tissue after 1 hour of controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hour
Glycerol level in microdialysate from liver tissue after controlled oxygenated rewarming machine perfusion - 1 hour	Microdialysis glycerol level in donor livers tissue after 1 hour of controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hour
Glucose level in microdialysate from liver tissue after controlled oxygenated rewarming machine perfusion - 1 hour	Microdialysis glucose level in donor livers tissue after 1 hour of controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hour
Pyruvate level in microdialysate from liver tissue after controlled oxygenated rewarming machine perfusion - 1 hour	Microdialysis pyruvate level in donor livers tissue after 1 hour of controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hour
Glucose level in microdialysate from liver tissue after normothermic machine perfusion - 2.5 hours	Microdialysis glucose level in donor liver tissue after 2.5 hours of normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Glucose level in microdialysate from liver tissue after normothermic machine perfusion - 4 hours	Microdialysis glucose level in donor liver tissue after 4 hours of normothermic machine perfusion in extended criteria donors livers.	4 hours
Pyruvate level in microdialysate from liver tissue after normothermic machine perfusion - 2.5 hours	Microdialysis pyruvate level in donor liver tissue after 2.5 hours of normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Pyruvate level in microdialysate from liver tissue after normothermic machine perfusion - 4 hours	Microdialysis pyruvate level in donor liver tissue after 4 hours of normothermic machine perfusion in extended criteria donors livers.	4 hours
Glycerol level in microdialysate from liver tissue after normothermic machine perfusion - 2.5 hours	Microdialysis glycerol level in donor liver tissue after 2.5 hours of normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Glycerol level in microdialysate from liver tissue after normothermic machine perfusion - 4 hours	Microdialysis glycerol level in donor liver tissue after 4 hours of normothermic machine perfusion in extended criteria donors livers.	4 hours
Lactate level in microdialysate from bile after normothermic machine perfusion - 4 hours	Microdialysis lactate level from bile after normothermic machine perfusion - 4 hours in extended criteria donors livers.	4 hours
Lactate level in microdialysate from bile after normothermic machine perfusion - 2.5 hours	Microdialysis lactate level from bile after normothermic machine perfusion - 2.5 hours in extended criteria donors livers.	2.5 hours
Glucose level in microdialysate from bile after normothermic machine perfusion - 4 hours	Microdialysis glucose levels from bile after normothermic machine perfusion - 4 hours in extended criteria donors livers.	4 hours
Glucose level in microdialysate from bile after normothermic machine perfusion - 2.5 hours	Microdialysis glucose levels from bile after normothermic machine perfusion - 2.5 hours in extended criteria donors livers.	2.5 hours
Pyruvate level in microdialysate from bile after normothermic machine perfusion - 4 hours	Microdialysis pyruvate levels from bile after normothermic machine perfusion - 4 hours in extended criteria donors livers.	4 hours
Pyruvate level in microdialysate from bile after normothermic machine perfusion - 2.5 hours	Microdialysis pyruvate levels from bile after normothermic machine perfusion - 2.5 hours in extended criteria donors livers.	2.5 hours
Glycerol level in microdialysate from bile after normothermic machine perfusion - 4 hours	Glycerol levels from bile after normothermic machine perfusion - 4 hours in extended criteria donors livers.	4 hours
Glycerol level in microdialysate from bile after normothermic machine perfusion - 2.5 hours	Glycerol levels from bile after normothermic machine perfusion - 2.5 hours in extended criteria donors livers.	2.5 hours
Glycerol level in microdialysate from bile after controlled oxygenated rewarming machine perfusion - 1 hour	Glycerol levels from bile after controlled oxygenated rewarming machine perfusion - 1 hour - in extended criteria donors livers.	1 hour
Glucose level in microdialysate from bile after controlled oxygenated rewarming machine perfusion - 1 hour	Glucose levels from bile after controlled oxygenated rewarming machine perfusion - 1 hour - in extended criteria donors livers.	1 hour
Lactate level in microdialysate from bile after controlled oxygenated rewarming machine perfusion - 1 hour	Lactate levels from bile after controlled oxygenated rewarming machine perfusion - 1 hour - in extended criteria donors livers.	1 hour
Pyruvate level in microdialysate from bile after controlled oxygenated rewarming machine perfusion - 1 hour	Pyruvate levels from bile after controlled oxygenated rewarming machine perfusion - 1 hour - in extended criteria donors livers.	1 hour
Pyruvate level in microdialysate from bile after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours	Pyruvate levels from bile after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours - in extended criteria donors livers.	2 hours
Glycerol level in microdialysate from bile after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours	Glycerol levels from bile after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours - in extended criteria donors livers.	2 hours
Lactate level in microdialysate from bile after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours	Lactate levels from bile after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours - in extended criteria donors livers.	2 hours
Glucose level in microdialysate from bile after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours	Glucose levels from bile after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours - in extended criteria donors livers.	2 hours
Bile gases pH - 4 hours after normothermic machine perfusion	Bile gas pH - 4 hours after normothermic machine perfusion in extended criteria donors livers.	4 hours
Bile gases pH - 2.5 hours after normothermic machine perfusion	Bile gas pH - 2.5 hours after normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Bile gases Lactate - 4 hours after normothermic machine perfusion	Bile gas Lactate - 4 hours after normothermic machine perfusion in extended criteria donors livers.	4 hours
Bile gases Lactate - 2.5 hours after normothermic machine perfusion	Bile gas Lactate - 2.5 hours after normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Bile gases Glucose - 4 hours after normothermic machine perfusion	Bile gas Glucose - 4 hours after normothermic machine perfusion in extended criteria donors livers.	4 hours
Bile gases Glucose - 2.5 hours after normothermic machine perfusion	Bile gas Glucose - 2.5 hours after normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Bile gases Oxygen (O2) - 4 hours after normothermic machine perfusion	Bile gas O2 - 4 hours after normothermic machine perfusion in extended criteria donors livers.	4 hours
Bile gases O2 - 2.5 hours after normothermic machine perfusion	Bile gas O2 - 2.5 hours after normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Bile gases carbon dioxide (CO2) - 4 hours after normothermic machine perfusion	Bile gas CO2 - 4 hours after normothermic machine perfusion in extended criteria donors livers.	4 hours
Bile gases CO2 - 2.5 hours after normothermic machine perfusion	Bile gas CO2 - 2.5 hours after normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Bile gases bicarbonate (HCO3) - 4 hours after normothermic machine perfusion	Bile gas HCO3 - 4 hours after normothermic machine perfusion in extended criteria donors livers.	4 hours
Bile gases HCO3 - 2.5 hours after normothermic machine perfusion	Bile gas HCO3 - 2.5 hours after normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Bile gases base excess (BE) - 4 hours after normothermic machine perfusion	Bile gas BE - 4 hours after normothermic machine perfusion in extended criteria donors livers.	4 hours
Ischemia/reperfusion injury - 4 hours after normothermic machine perfusion	Ischemia/reperfusion injury in liver biopsies, graded according to Ali JM et al, Liver transplant 2015; nil, mild, moderate, and severe. - 4 hours after normothermic machine perfusion in extended criteria donors livers.	4 hours
Ischemia/reperfusion damage - 4 hours after normothermic machine perfusion	Ischemia/reperfusion damage in liver biopsies, graded according to Suzuki score (Tian Y et al, Stem Cell Research & Therapy, 2016); score 0, 1, 2, 3, (0=none, 4= severe) - 4 hours after normothermic machine perfusion in extended criteria donors livers.	4 hours
Ischemia/reperfusion injury - after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion	Ischemia/reperfusion injury in liver biopsies, graded according to Tian Y et al et al, Liver transplant 2015; nil, mild, moderate, and severe. - after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	4 hours
Ischemia/reperfusion damage - after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion	Ischemia/reperfusion damage in liver biopsies, graded according to Suzuki score (Tian Y et al, Stem Cell Research & Therapy, 2016); score 0, 1, 2, 3, (0=none, 4= severe) - after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	4 hours
Ischemia/reperfusion injury - before machine perfusion	Ischemia/reperfusion injury in liver biopsies, graded according to Ali JM et al, Liver transplant 2015; nil, mild, moderate, and severe. - before machine perfusion in extended criteria donors livers	1 minute
Ischemia/reperfusion damage - before machine perfusion	Ischemia/reperfusion damage in liver biopsies, graded according to Suzuki score (Tian Y et al, Stem Cell Research & Therapy, 2016); score 0, 1, 2, 3, (0=none, 4= severe) - before machine perfusion in extended criteria donors livers	1 minute
Ischemia/reperfusion injury - after controlled oxygenated rewarming machine perfusion - 1 hour	Ischemia/reperfusion injury in liver biopsies, graded according to Ali JM et al, Liver transplant 2015; nil, mild, moderate, and severe - after controlled oxygenated rewarming machine perfusion - 1 hour in extended criteria donors livers	1 hour
Ischemia/reperfusion damage - after controlled oxygenated rewarming machine perfusion - 1 hour	Ischemia/reperfusion damage in liver biopsies, graded according to Suzuki score (Tian Y et al, Stem Cell Research & Therapy, 2016); score 0, 1, 2, 3, (0=none, 4= severe) - after controlled oxygenated rewarming machine perfusion - 1 hour in extended criteria donors livers	1 hour
Ischemia/reperfusion injury - 2.5 hours after normothermic machine perfusion	Ischemia/reperfusion injury in liver biopsies, graded according to Ali JM et al, Liver transplant 2015; nil, mild, moderate, and severe. - 2.5 hours after normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Ischemia/reperfusion damage - 2.5 hours after normothermic machine perfusion	Ischemia/reperfusion damage in liver biopsies, graded according to Suzuki score (Tian Y et al, Stem Cell Research & Therapy, 2016); score 0, 1, 2, 3, (0=none, 4= severe) - 2.5 hours after normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Bile gases BE - 2.5 hours after normothermic machine perfusion	Bile gas BE - 2.5 hours after normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Bile gases oxygen saturation (SO2) - 4 hours after normothermic machine perfusion	Bile gas SO2- 4 hours after normothermic machine perfusion in extended criteria donors livers.	4 hours
Bile gases SO2 - 2.5 hours after normothermic machine perfusion	Bile gas SO2- 2.5 hours after normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Bile gases hemoglobin (Hb)- 4 hours after normothermic machine perfusion	Bile gas Hb - 4 hours after normothermic machine perfusion in extended criteria donors livers.	4 hours
Bile gases Hb - 2.5 hours after normothermic machine perfusion	Bile gas Hb - 2.5 hours after normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Bile gases sodium (Na) - 4 hours after normothermic machine perfusion	Bile gas Na - 4 hours after normothermic machine perfusion in extended criteria donors livers.	4 hours
Bile gases Na - 2.5 hours after normothermic machine perfusion	Bile gas Na - 2.5 hours after normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Bile gases potassium (K) - 4 hours after normothermic machine perfusion	Bile gas K - 4 hours after normothermic machine perfusion in extended criteria donors livers.	4 hours
Bile gases K - 2.5 hours after normothermic machine perfusion	Bile gas K - 2.5 hours after normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Bile gases Calcium (Ca) - 4 hours after normothermic machine perfusion	Bile gas Ca - 4 hours after normothermic machine perfusion in extended criteria donors livers.	4 hours
Bile gases Ca - 2.5 hours after normothermic machine perfusion	Bile gas Ca - 2.5 hours after normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Markers of injury, inflammation - 2.5 hours after normothermic machine perfusion	Markers of injury, inflammation - 2.5 hours after normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Bile gas lactate 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion	Bile gas lactate 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Markers of injury, inflammation 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion	Markers of injury, inflammation 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Bile gas Glucose 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion	Bile gas Glucose 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Bile gas pH 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion	Bile gas pH 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Bile gas O2 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion	Bile gas O2 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Bile gas CO2 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion	Bile gas CO2 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Bile gas HCO3 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion	Bile gas HCO3 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Bile gas SO2 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion	Bile gas SO2 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Bile gas Hemoglobin 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion	Bile gas Hemoglobin 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Bile gas Na 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion	Bile gas Na 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Bile gas K 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion	Bile gas K 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Bile gas Ca 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion	Bile gas Ca 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Bile gas BE 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion	Bile gas BE 2 hours after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Markers of injury, inflammation 1 hour after controlled oxygenated rewarming machine perfusion	Markers of injury, inflammation 1 hour after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hour
Bile gas lactate 1 hour after controlled oxygenated rewarming machine perfusion	Bile gas lactate 1 hour after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hours
Bile gas Glucose 1 hour after controlled oxygenated rewarming machine perfusion	Bile gas Glucose 1 hour after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hours
Bile gas pH 1 hour after controlled oxygenated rewarming machine perfusion	Bile gas pH 1 hour after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hours
Markers of injury, inflammation 1 hour after controlled oxygenated rewarming machine perfusion	Markers of injury, inflammation 1 hour after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hours
Bile gas O2 1 hour after controlled oxygenated rewarming machine perfusion	Bile gas O2 1 hour after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hours
Bile gas CO2 1 hour after controlled oxygenated rewarming machine perfusion	Bile gas CO2 1 hour after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hours
Bile gas HCO3 1 hour after controlled oxygenated rewarming machine perfusion	Bile gas HCO3 1 hour after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hours
Bile gas BE 1 hour after controlled oxygenated rewarming machine perfusion	Bile gas BE 1 hour after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hours
Bile gas SO2 1 hour after controlled oxygenated rewarming machine perfusion	Bile gas SO2 1 hour after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hours
Bile gas hemoglobin 1 hour after controlled oxygenated rewarming machine perfusion	Bile gas hemoglobin 1 hour after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hours
Bile gas Na 1 hour after controlled oxygenated rewarming machine perfusion	Bile gas Na 1 hour after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hours
Bile gas K 1 hour after controlled oxygenated rewarming machine perfusion	Bile gas K 1 hour after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hours
Bile gas Ca 1 hour after controlled oxygenated rewarming machine perfusion	Bile gas Ca 1 hour after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hours
Perfusate gas Ca - during machine perfusion	Perfusate gas Ca during machine perfusion in extended criteria donors livers.	24 hours
Perfusate gas pH - during machine perfusion	Perfusate gas pH during machine perfusion in extended criteria donors livers.	24 hours
Perfusate gas SO2 - during machine perfusion	Perfusate gas SO2 during machine perfusion in extended criteria donors livers.	24 hours
Perfusate gas O2 - during machine perfusion	Perfusate gas O2 during machine perfusion in extended criteria donors livers.	24 hours
Perfusate gas CO2 - during machine perfusion	Perfusate gas CO2 during machine perfusion in extended criteria donors livers.	24 hours
Perfusate gas K - during machine perfusion	Perfusate gas K during machine perfusion in extended criteria donors livers.	24 hours
Perfusate gas Na - during machine perfusion	Perfusate gas Na during machine perfusion in extended criteria donors livers.	24 hours
Perfusate gas BE - during machine perfusion	Perfusate gas BE during machine perfusion in extended criteria donors livers.	24 hours
Perfusate gas HCO3 - during machine perfusion	Perfusate gas HCO3 during machine perfusion in extended criteria donors livers.	24 hours
Perfusate gas hemoglobin - during machine perfusion	Perfusate gas hemoglobin during machine perfusion in extended criteria donors livers.	24 hours
Perfusate gas lactate - during machine perfusion	Perfusate gas lactate during machine perfusion in extended criteria donors livers.	24 hours
Perfusate gas glucose - during machine perfusion	Perfusate gas glucose during machine perfusion in extended criteria donors livers.	24 hours
Postoperative complications	According to Clavien Dindo Classification	12 months
Length of stay	Length of initial ICU and initial hospital stay is determined in days of admission following liver transplantation.	4 months
Machine flow during controlled oxygenated rewarming	Machine flow (millilitre/hour)	1 hour
Machine flow during Dual-end-ischemic Hypothermic Oxygenated Perfusion	Machine flow (millilitre/hour)	1 hour
Machine pressure during controlled oxygenated rewarming	Machine pressure ((millimetre Hg))	1 hour
Machine pressure during Dual-end-ischemic Hypothermic Oxygenated Perfusion	Machine pressure ((millimetre Hg))	1 hour
Machine Fraction of oxygen during controlled oxygenated rewarming	Machine fraction of oxygen (%)	1 hour
Machine Fraction of oxygen Dual-end-ischemic Hypothermic Oxygenated Perfusion	Machine fraction of oxygen (%)	1 hour
Machine Resistance during controlled oxygenated rewarming	Machine Resistance (millilitre/minute/millimetre Hg)	1 hour
Machine Resistance during Dual-end-ischemic Hypothermic Oxygenated Perfusion	Machine Resistance (millilitre/minute/millimetre Hg)	1 hour
Machine flow during Dual-end-ischemic Hypothermic Oxygenated Perfusion	Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion flow (millilitre/hour)	2 hours
Machine flow during normothermic machine perfusion	Machine flow during normothermic machine perfusion (millilitre/hour)	4 hours
Machine flow during normothermic machine perfusion	Machine flow during normothermic machine perfusion (millilitre/hour)	2.5 hours
Machine pressure during normothermic machine perfusion	Machine pressure (millimetre Hg)	4 hours
Machine pressure during normothermic machine perfusion	Machine pressure (millimetre Hg)	2.5 hours
Machine Fraction of oxygen during normothermic machine perfusion	Machine fraction of oxygen (%)	4 hours
Machine Fraction of oxygen during normothermic machine perfusion	Machine fraction of oxygen (%)	2.5 hours
Machine Resistance during normothermic machine perfusion	Machine Resistance (millilitre/minute/millimetre Hg)	4 hours
Machine Resistance during normothermic machine perfusion	Machine Resistance (millilitre/minute/millimetre Hg)	2.5 hours
Total preservation time	Total preservation time (machine perfusion time)	48 hours
Alanine amino transferase in perfusate during machine perfusion	Alanine amino transferase in perfusate during machine perfusion (U/Litre)	24 hours
Aspartate amino transferase in perfusate during machine perfusion	Aspartate amino transferase in perfusate during machine perfusion (U/Litre)	24 hours
Alkaline phosphatase in perfusate during machine perfusion	Aspartate amino transferase in perfusate during machine perfusion (U/Litre)	24 hours
Gamma-glutamyl transferase in perfusate during machine perfusion	Gamma-glutamyl transferase in perfusate during machine perfusion (U/Litre)	24 hours
Urea in perfusate during machine perfusion	Urea in perfusate during machine perfusion (millimol/Litre)	24 hours
Bilirubin in perfusate during machine perfusion	Bilirubin in perfusate during machine perfusion (micromol/Litre)	24 hours
Not yet decided types of cytokines/interleukins, endothelium markers, miRNA's in perfusate during machine perfusion	Different cytokines/interleukins, endothelium markers, miRNA's in perfusate during machine perfusion	24 hours
Not yet decided types of cytokines/interleukins, endothelium markers, miRNA's in liver tissue during machine perfusion	Different cytokines/interleukins, endothelium markers, miRNA's in liver tissue during machine perfusion	24 hours
Not yet decided types of cytokines/interleukins, endothelium markers, miRNA's in bile during machine perfusion	Different cytokines/interleukins, endothelium markers, miRNA's in bile during machine perfusion	24 hours
Histopathology - liver tissue. Mitochondrial function	Histological analysis of parenchymal biopsies which are assessed for mitochondrial function.	During machine perfusion - 24 hours
Histopathology - bile duct. Mitochondrial function	Histological analysis of bile duct biopsies which are assessed for mitochondrial function.	During machine perfusion - 24 hours
Histopathology - liver tissue. Perfusion/reperfusion injury	Histological analysis of parenchymal biopsies which are assessed for perfusion/reperfusion injury	During machine perfusion - 24 hours
Histopathology - bile duct. Perfusion/reperfusion injury	Histological analysis of bile duct biopsies which are assessed for perfusion/reperfusion injury	During machine perfusion - 24 hours
Histopathology - liver tissue. Cell death	Histological analysis of parenchymal biopsies which are assessed for cell death	During machine perfusion - 24 hours
Histopathology - bile duct. Cell death	Histological analysis of bile duct biopsies which are assessed for cell death	During machine perfusion - 24 hours
Histopathology - liver tissue. Inflammation	Histological analysis of parenchymal biopsies which are assessed for inflammation	During machine perfusion - 24 hours
Histopathology - bile duct. Inflammation	Histological analysis of bile duct biopsies which are assessed for inflammation	During machine perfusion - 24 hours
Histopathology - liver tissue. Metabolomics	Histological analysis of parenchymal biopsies which are assessed for metabolomics	During machine perfusion - 24 hours
Histopathology - bileduct. Metabolomics	Histological analysis of bile duct biopsies which are assessed for metabolomics	During machine perfusion - 24 hours
Histopathology - liver tissue. Lipidomics	Histological analysis of parenchymal biopsies which are assessed for lipidomics	During machine perfusion - 24 hours
Histopathology - bile duct. Lipidomics	Histological analysis of bile duct biopsies which are assessed for lipidomics	During machine perfusion - 24 hours
Histopathology - liver tissue. RNA sequencing	Histological analysis of parenchymal biopsies which are assessed for RNA sequencing	During machine perfusion - 24 hours
Histopathology - bile duct. RNA sequencing	Histological analysis of bile duct biopsies which are assessed for RNA sequencing	During machine perfusion - 24 hours
Histopathology - liver tissue. Endothelium properties	Histological analysis of parenchymal biopsies which are assessed for endothelium properties	During machine perfusion - 24 hours
Histopathology - bile duct. Endothelium properties	Histological analysis of bile duct biopsies which are assessed for endothelium properties	During machine perfusion - 24 hours
International normalized ratio on postoperative day 7	Blood sample from recipient: International normalized ratio on postoperative day 7	7 postoperative day
Alanine amino transferase postoperative day 0	Alanine amino transferase postoperative day 0 in the donated recipients (U/Litre)	Postoperative day 0
Aspartate amino transferase postoperative day 0	Aspartate amino transferase postoperative day 0 in the donated recipients (U/Litre)	Postoperative day 0
Alkaline phosphatase postoperative day 0	Alkaline phosphatase postoperative day 0 in the donated recipients (U/Litre)	Postoperative day 0
Gamma-glutamyl transferase postoperative day 0	Gamma-glutamyl transferase postoperative day 0 in the donated recipients (U/Litre)	Postoperative day 0
Urea postoperative day 0	Urea postoperative day 0 in the donated recipients (millimol/Litre)	Postoperative day 0
Bilirubin postoperative day 0	Bilirubin postoperative day 0 in the donated recipients (micromol/Litre)	Postoperative day 0
Bilirubin postoperative day 1	Bilirubin postoperative day 1 in the donated recipients (micromol/Litre)	Postoperative day 1
Bilirubin postoperative day 2	Bilirubin postoperative day 2 in the donated recipients (micromol/Litre)	Postoperative day 2
Bilirubin postoperative day 3	Bilirubin postoperative day 3 in the donated recipients (micromol/Litre)	Postoperative day 3
Bilirubin postoperative day 4	Bilirubin postoperative day 4 in the donated recipients (micromol/Litre)	Postoperative day 4
Bilirubin postoperative day 5	Bilirubin postoperative day 5 in the donated recipients (micromol/Litre)	Postoperative day 5
Bilirubin postoperative day 6	Bilirubin postoperative day 6 in the donated recipients (micromol/Litre)	Postoperative day 6
Bilirubin postoperative day 7	Bilirubin postoperative day 7 in the donated recipients (micromol/Litre)	Postoperative day 7
Urea postoperative day 1	Urea postoperative day 1 in the donated recipients (millimol/Litre)	Postoperative day 1
Urea postoperative day 2	Urea postoperative day 2 in the donated recipients (millimol/Litre)	Postoperative day 2
Urea postoperative day 3	Urea postoperative day 3 in the donated recipients (millimol/Litre)	Postoperative day 3
Urea postoperative day 4	Urea postoperative day 4 in the donated recipients (millimol/Litre)	Postoperative day 4
Urea postoperative day 5	Urea postoperative day 5 in the donated recipients (millimol/Litre)	Postoperative day 5
Urea postoperative day 6	Urea postoperative day 6 in the donated recipients (millimol/Litre)	Postoperative day 6
Urea postoperative day 7	Urea postoperative day 7 in the donated recipients (millimol/Litre)	Postoperative day 7
Aspartate amino transferase postoperative day 1	Aspartate amino transferase postoperative day 1 in the donated recipients (U/Litre)	Postoperative day 1
Alkaline phosphatase postoperative day 1	Alkaline phosphatase postoperative day 1 in the donated recipients (U/Litre)	Postoperative day 1
Gamma-glutamyl transferase postoperative day 1	Gamma-glutamyl transferase postoperative day 1 in the donated recipients (U/Litre)	Postoperative day 1
Alanine amino transferase postoperative day 2	Alanine amino transferase postoperative day 2 in the donated recipients (U/Litre)	Postoperative day 2
Aspartate amino transferase postoperative day 2	Aspartate amino transferase postoperative day 2 in the donated recipients (U/Litre)	Postoperative day 2
Alkaline phosphatase postoperative day 2	Alkaline phosphatase postoperative day 2 in the donated recipients (U/Litre)	Postoperative day 2
Gamma-glutamyl transferase postoperative day 2	Gamma-glutamyl transferase postoperative day 2 in the donated recipients (U/Litre)	Postoperative day 2
Alanine amino transferase postoperative day 3	Alanine amino transferase postoperative day 3 in the donated recipients (U/Litre)	Postoperative day 3
Aspartate amino transferase postoperative day 3	Aspartate amino transferase postoperative day 3 in the donated recipients (U/Litre)	Postoperative day 3
Alkaline phosphatase postoperative day 3	Alkaline phosphatase postoperative day 3 in the donated recipients (U/Litre)	Postoperative day 3
Gamma-glutamyl transferase postoperative day 3	Gamma-glutamyl transferase postoperative day 3 in the donated recipients (U/Litre)	Postoperative day 3
Alanine amino transferase postoperative day 4	Alanine amino transferase postoperative day 4 in the donated recipients (U/Litre)	Postoperative day 4
Aspartate amino transferase postoperative day 4	Aspartate amino transferase postoperative day 4 in the donated recipients (U/Litre)	Postoperative day 4
Alkaline phosphatase postoperative day 4	Alkaline phosphatase postoperative day 4 in the donated recipients (U/Litre)	Postoperative day 4
Gamma-glutamyl transferase postoperative day 4	Gamma-glutamyl transferase postoperative day 4 in the donated recipients (U/Litre)	Postoperative day 4
Alanine amino transferase postoperative day 5	Alanine amino transferase postoperative day 5 in the donated recipients (U/Litre)	Postoperative day 5
Aspartate amino transferase postoperative day 5	Aspartate amino transferase postoperative day 5 in the donated recipients (U/Litre)	Postoperative day 5
Alkaline phosphatase postoperative day 5	Alkaline phosphatase postoperative day 5 in the donated recipients (U/Litre)	Postoperative day 5
Gamma-glutamyl transferase postoperative day 5	Gamma-glutamyl transferase postoperative day 5 in the donated recipients (U/Litre)	Postoperative day 5
Alanine amino transferase postoperative day 6	Alanine amino transferase postoperative day 6 in the donated recipients (U/Litre)	Postoperative day 6
Aspartate amino transferase postoperative day 6	Aspartate amino transferase postoperative day 6 in the donated recipients (U/Litre)	Postoperative day 6
Alkaline phosphatase postoperative day 6	Aspartate amino transferase postoperative day 6 in the donated recipients (U/Litre)	Postoperative day 6
Gamma-glutamyl transferase postoperative day 6	Gamma-glutamyl transferase postoperative day 6 in the donated recipients (U/Litre)	Postoperative day 6
Alanine amino transferase postoperative day 7	Alanine amino transferase postoperative day 7 in the donated recipients (U/Litre)	Postoperative day 7
Aspartate amino transferase postoperative day 7	Aspartate amino transferase postoperative day 7 in the donated recipients (U/Litre)	Postoperative day 7
Alkaline phosphatase postoperative day 7	Alkaline phosphatase postoperative day 7 in the donated recipients (U/Litre)	Postoperative day 7
Gamma-glutamyl transferase postoperative day 7	Gamma-glutamyl transferase postoperative day 7 in the donated recipients (U/Litre)	Postoperative day 7
Alanine amino transferase postoperative month 1	Alanine amino transferase postoperative month 1 in the donated recipients (U/Litre)	1 month after surgery
Aspartate amino transferase postoperative month 1	Aspartate amino transferase postoperative month 1 in the donated recipients (U/Litre)	1 month after surgery
Alkaline phosphatase postoperative month 1	Alkaline phosphatase postoperative month 1 in the donated recipients (U/Litre)	1 month after surgery
Gamma-glutamyl transferase postoperative month 1	Gamma-glutamyl transferase postoperative month 1 in the donated recipients (U/Litre)	1 month after surgery
Urea postoperative month 1	Urea postoperative month 1 in the donated recipients (millimol/Litre)	1 month after surgery
Bilirubin postoperative month 1	Bilirubin postoperative month 1 in the donated recipients (micromol/Litre)	1 month after surgery
Bilirubin postoperative month 2	Bilirubin postoperative month 2 in the donated recipients (micromol/Litre)	2 month after surgery
Bilirubin postoperative month 3	Bilirubin postoperative month 3 in the donated recipients (micromol/Litre)	3 month after surgery
Bilirubin postoperative month 4	Bilirubin postoperative month 4 in the donated recipients (micromol/Litre)	4 month after surgery
Bilirubin postoperative month 5	Bilirubin postoperative month 5 in the donated recipients (micromol/Litre)	5 month after surgery
Bilirubin postoperative month 6	Bilirubin postoperative month 6 in the donated recipients (micromol/Litre)	6 month after surgery
Bilirubin postoperative month 7	Bilirubin postoperative month 7 in the donated recipients (micromol/Litre)	7 month after surgery
Bilirubin postoperative month 8	Bilirubin postoperative month 8 in the donated recipients (micromol/Litre)	8 month after surgery
Bilirubin postoperative month 9	Bilirubin postoperative month 9 in the donated recipients (micromol/Litre)	9 month after surgery
Bilirubin postoperative month 10	Bilirubin postoperative month 10 in the donated recipients (micromol/Litre)	10 month after surgery
Bilirubin postoperative month 11	Bilirubin postoperative month 11 in the donated recipients (micromol/Litre)	11 month after surgery
Bilirubin postoperative month 12	Bilirubin postoperative month 12 in the donated recipients (micromol/Litre)	12 month after surgery
Urea postoperative month 2	Urea postoperative month 2 in the donated recipients (millimol/Litre)	2 month after surgery
Urea postoperative month 3	Urea postoperative month 3 in the donated recipients (millimol/Litre)	3 month after surgery
Urea postoperative month 4	Urea postoperative month 4 in the donated recipients (millimol/Litre)	4 month after surgery
Urea postoperative month 5	Urea postoperative month 5 in the donated recipients (millimol/Litre)	5 month after surgery
Urea postoperative month 6	Urea postoperative month 6 in the donated recipients (millimol/Litre)	6 month after surgery
Urea postoperative month 7	Urea postoperative month 7 in the donated recipients (millimol/Litre)	7 month after surgery
Urea postoperative month 8	Urea postoperative month 8 in the donated recipients (millimol/Litre)	8 month after surgery
Urea postoperative month 9	Urea postoperative month 9 in the donated recipients (millimol/Litre)	9 month after surgery
Urea postoperative month 10	Urea postoperative month 10 in the donated recipients (millimol/Litre)	10 month after surgery
Urea postoperative month 11	Urea postoperative month 11 in the donated recipients (millimol/Litre)	11 month after surgery
Urea postoperative month 12	Urea postoperative month 12 in the donated recipients (millimol/Litre)	12 month after surgery
Alanine amino transferase postoperative month 2	Alanine amino transferase postoperative month 2 in the donated recipients (U/Litre)	2 month after surgery
Aspartate amino transferase postoperative month 2	Aspartate amino transferase postoperative month 2 in the donated recipients (U/Litre)	2 month after surgery
Alkaline phosphatase postoperative month 2	Alkaline phosphatase postoperative month 2 in the donated recipients (U/Litre)	2 month after surgery
Gamma-glutamyl transferase postoperative month 2	Gamma-glutamyl transferase postoperative month 2 in the donated recipients (U/Litre)	2 month after surgery
Alanine amino transferase postoperative month 3	Alanine amino transferase postoperative month 3 in the donated recipients (U/Litre)	3 month after surgery
Aspartate amino transferase postoperative month 3	Aspartate amino transferase postoperative month 3 in the donated recipients (U/Litre)	3 month after surgery
Alkaline phosphatase postoperative month 3	Alkaline phosphatase postoperative month 3 in the donated recipients (U/Litre)	3 month after surgery
Gamma-glutamyl transferase postoperative month 3	Gamma-glutamyl transferase postoperative month 3 in the donated recipients (U/Litre)	3 month after surgery
Alanine amino transferase postoperative month 4	Alanine amino transferase postoperative month 4 in the donated recipients (U/Litre)	4 month after surgery
Aspartate amino transferase postoperative month 4	Aspartate amino transferase postoperative month 4 in the donated recipients (U/Litre)	4 month after surgery
Alkaline phosphatase postoperative month 4	Alkaline phosphatase postoperative month 4 in the donated recipients (U/Litre)	4 month after surgery
Gamma-glutamyl transferase postoperative month 4	Gamma-glutamyl transferase postoperative month 4 in the donated recipients (U/Litre)	4 month after surgery
Alanine amino transferase postoperative month 5	Alanine amino transferase postoperative month 5 in the donated recipients (U/Litre)	5 month after surgery
Aspartate amino transferase postoperative month 5	Aspartate amino transferase postoperative month 5 in the donated recipients (U/Litre)	5 month after surgery
Alkaline phosphatase postoperative month 5	Alkaline phosphatase postoperative month 5 in the donated recipients (U/Litre)	5 month after surgery
Gamma-glutamyl transferase postoperative month 5	Gamma-glutamyl transferase postoperative month 5 in the donated recipients (U/Litre)	5 month after surgery
Alanine amino transferase postoperative month 6	Alanine amino transferase postoperative month 6 in the donated recipients (U/Litre)	6 month after surgery
Aspartate amino transferase postoperative month 6	Aspartate amino transferase postoperative month 6 in the donated recipients (U/Litre)	6 month after surgery
Alkaline phosphatase postoperative month 6	Alkaline phosphatase postoperative month 6 in the donated recipients (U/Litre)	6 month after surgery
Gamma-glutamyl transferase postoperative month 6	Gamma-glutamyl transferase postoperative month 6 in the donated recipients (U/Litre)	6 month after surgery
Alanine amino transferase postoperative month 7	Alanine amino transferase postoperative month 7 in the donated recipients (U/Litre)	7 month after surgery
Aspartate amino transferase postoperative month 7	Aspartate amino transferase postoperative month 7 in the donated recipients (U/Litre)	7 month after surgery
Alkaline phosphatase postoperative month 7	Alkaline phosphatase postoperative month 7 in the donated recipients (U/Litre)	7 month after surgery
Gamma-glutamyl transferase postoperative month 7	Gamma-glutamyl transferase postoperative month 7 in the donated recipients (U/Litre)	7 month after surgery
Alanine amino transferase postoperative month 8	Alanine amino transferase postoperative month 8 in the donated recipients (U/Litre)	8 month after surgery
Aspartate amino transferase postoperative month 8	Aspartate amino transferase postoperative month 8 in the donated recipients (U/Litre)	8 month after surgery
Alkaline phosphatase postoperative month 8	Alkaline phosphatase postoperative month 8 in the donated recipients (U/Litre)	8 month after surgery
Gamma-glutamyl transferase postoperative month 8	Gamma-glutamyl transferase postoperative month 8 in the donated recipients (U/Litre)	8 month after surgery
Alanine amino transferase postoperative month 9	Alanine amino transferase postoperative month 9 in the donated recipients (U/Litre)	9 month after surgery
Aspartate amino transferase postoperative month 9	Aspartate amino transferase postoperative month 9 in the donated recipients (U/Litre)	9 month after surgery
Alkaline phosphatase postoperative month 9	Alkaline phosphatase postoperative month 9 in the donated recipients (U/Litre)	9 month after surgery
Gamma-glutamyl transferase postoperative month 9	Gamma-glutamyl transferase postoperative month 9 in the donated recipients (U/Litre)	9 month after surgery
Alanine amino transferase postoperative month 10	Alanine amino transferase postoperative month 10 in the donated recipients (U/Litre)	10 month after surgery
Aspartate amino transferase postoperative month 10	Aspartate amino transferase postoperative month 10 in the donated recipients (U/Litre)	10 month after surgery
Alkaline phosphatase postoperative month 10	Alkaline phosphatase postoperative month 10 in the donated recipients (U/Litre)	10 month after surgery
Gamma-glutamyl transferase postoperative month 10	Gamma-glutamyl transferase postoperative month 10 in the donated recipients (U/Litre)	10 month after surgery
Alanine amino transferase postoperative month 11	Alanine amino transferase postoperative month 11 in the donated recipients (U/Litre)	11 month after surgery
Aspartate amino transferase postoperative month 11	Aspartate amino transferase postoperative month 11 in the donated recipients (U/Litre)	11 month after surgery
Alkaline phosphatase postoperative month 11	Alkaline phosphatase postoperative month 11 in the donated recipients (U/Litre)	11 month after surgery
Gamma-glutamyl transferase postoperative month 11	Gamma-glutamyl transferase postoperative month 11 in the donated recipients (U/Litre)	11 month after surgery
Alanine amino transferase postoperative month 12	Alanine amino transferase postoperative month 12 in the donated recipients (U/Litre)	12 month after surgery
Aspartate amino transferase postoperative month 12	Aspartate amino transferase postoperative month 12 in the donated recipients (U/Litre)	12 month after surgery
Alkaline phosphatase postoperative month 12	Alkaline phosphatase postoperative month 12 in the donated recipients (U/Litre)	12 month after surgery
Gamma-glutamyl transferase postoperative month 12	Gamma-glutamyl transferase postoperative month 12 in the donated recipients (U/Litre)	12 month after surgery
Postoperative microdialysis levels of lactate	Postoperative microdialysis levels of lactate in transplanted livers the first 14 postoperative days	14 days
Postoperative microdialysis levels of pyruvate	Postoperative microdialysis levels of pyruvate in transplanted livers the first 14 postoperative days	14 days
Postoperative microdialysis levels of glycerol	Postoperative microdialysis levels of glycerol in transplanted livers the first 14 postoperative days	14 days
Postoperative microdialysis levels of glucose	Postoperative microdialysis levels of glucose in transplanted livers the first 14 postoperative days	14 days
Systolic blood pressure	Systolic blood pressure (millimeter Hg)	From 5 min before reperfusion, up to 20 minutes after reperfusion
Diastolic blood pressure	Diastolic blood pressure (millimeter Hg)	From 5 min before reperfusion, up to 20 minutes after reperfusion
Heart rate	Heart rate (Beats/minute)	From 5 min before reperfusion, up to 20 minutes after reperfusion
Vasopressor dosage	Vasopressor dosage (microgram/kilogram/minutes)	From 5 min before reperfusion, up to 20 minutes after reperfusion
Patient survival	Patient survival (days)	Through study completion, an average of 12 months
Graft survival	Graft (censored and uncensored for patient death) survival (days)	Through study completion, an average of 12 months
Number of deaths	Number of deaths first 7 days after transplantation	7 days after transplantation
Number of retransplantation	Number of retransplantation first 7 days after transplantation	7 days after transplantation
Incidens of new onset diabetes after transplantation	New onset diabetes after transplantation after transplantation. New onset diabetes after transplantation is defined according to the World Health Organization criteria (Report 2003 S5-20).	Through study completion, an average of 12 months
Estimated glomerular filtration rate - Renal function	Estimated glomerular filtration rate according to the 4-variable Modification of Diet in Renal Disease equation.	Through study completion, an average of 12 months
The incidence of symptomatic Non-anastomotic Biliary Strictures	The incidence of symptomatic non-anastomotic biliary strictures	6 months
The incidence of asymptomatic Non-anastomotic Biliary Strictures	The incidence of asymptomatic non-anastomotic biliary strictures	6 months
The incidence of asymptomatic Non-anastomotic Biliary Strictures	The incidence of asymptomatic non-anastomotic biliary strictures	12 months
The incidence of symptomatic Non-anastomotic Biliary Strictures	The incidence of symptomatic non-anastomotic biliary strictures	12 months
The severity of Non-anastomotic Biliary Strictures	The severity of Non-anastomotic Biliary Strictures based on a scoring system described by Buis et. al (mild, moderate, or severe)	Through study completion, an average of 12 months
The location of Non-anastomotic Biliary Strictures	The location of Non-anastomotic Biliary Strictures is assessed by images of the magnetic resonance cholangiopancreatography	Through study completion, an average of 12 months
The incidence of infections	The incidence of infections leading to administration of antibiotics/antifungal/antiviral treatment	Through study completion, an average of 12 months
Lactate level in microdialysate from liver tissue - 4 hours	Microdialysis lactate level in donor liver tissue after 4 hours of normothermic machine perfusion in extended criteria donors livers.	4 hours
Pyruvate level in microdialysate from hilar plate after normothermic machine perfusion - 4 hours	Pyruvate level in microdialysate from hilar plate after normothermic machine perfusion in extended criteria donors livers.	4 hours
Glycerol level in microdialysate from hilar plate after normothermic machine perfusion - 4 hours	Glycerol level in microdialysate from hilar plate after normothermic machine perfusion in extended criteria donors livers.	4 hours
Glucose level in microdialysate from hilar plate after normothermic machine perfusion - 4 hours	Glucose level in microdialysate from hilar plate after normothermic machine perfusion in extended criteria donors livers.	4 hours
Glycerol level in microdialysate from hilar plate after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours	Glycerol level in microdialysate from hilar plate after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Lactate level in microdialysate from hilar plate after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours	Lactate level in microdialysate from hilar plate after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hours
Glucose level in microdialysate from hilar plate after controlled oxygenated rewarming machine perfusion - 1 hour	Glucose level in microdialysate from hilar plate after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hour
Pyruvate level in microdialysate from hilar plate after controlled oxygenated rewarming machine perfusion - 1 hour	Pyruvate level in microdialysate from hilar plate after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hour
Glycerol level in microdialysate from hilar plate after controlled oxygenated rewarming machine perfusion - 1 hour	Glycerol level in microdialysate from hilar plate after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hour
Lactate level in microdialysate from hilar plate after controlled oxygenated rewarming machine perfusion - 1 hour	Lactate level in microdialysate from hilar plate after controlled oxygenated rewarming machine perfusion in extended criteria donors livers.	1 hour
Glucose level in microdialysate from hilar plate after of Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers - 2 hours	Glucose level in microdialysate from hilar plate after of Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hour
Pyruvate level in microdialysate from hilar plate after of Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers - 2 hours	Pyruvate level in microdialysate from hilar plate after of Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion in extended criteria donors livers.	2 hour

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Donor associated variables - age	Age of the donor (years)	1 hour
Donor associated variables - liver steatosis	Assessment of liver steatosis (%)	1 hour
Donor associated variables - gender	Gender of donor	1 hour
Donor associated variables - Body mass index	Body mass index of donor (kilogram/meter2)	1 hour
Donor associated variables - weight of the liver	Weight of the liver (gram)	1 hour
Ischemia time - warm	Estimation of warm ischemia time (minutes)	12 hour
Ischemia time - cold	Estimation of cold ischemia time (minutes)	12 hour
Donor associated variables - Donor risk index	Donor risk index score - Increasing donor risk index is associated with higher discard rates among deceased donor livers procured for transplant. Low value of 1= best prognosis. High value of 40 = worst prognosis	1 hour

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: South-Eastern Norway Regional Health Authority
• Investigators: Principal Investigator: Søren E Pischke, MD, PhD, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: April 4, 2023
• First Submitted That Met QC Criteria: July 15, 2023
• First Posted (Actual): July 18, 2023

Study Record Updates

• Last Update Posted (Actual): November 1, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Microdialysis; Transplantation; Liver; Perfusion; Normothermic Machine Perfusion; Dual-end-ischemic Hypothermic Oxygenated Perfusion; Controlled Oxygenated Rewarming
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms
• Other Study ID Numbers: 598448

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Due to Norwegian laws individual participant data are not shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No