Interest of Oxygenated Hypothermic Perfusion (PHO) in Preservation of Hepatic Grafts From Expanded Criteria Donors

Study Overview
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Brief Summary
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Interest of oxygenated hypothermic perfusion in preservation of hepatic grafts from expanded criteria donors.

Detailed Description
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The excellent results of liver transplantation (LT) have led to a significant increase in the number of patients awaiting transplantation. At the same time, the number of grafts remains stable. To extend the donor pool, the use of Extended Criteria Donor (ECD) donors graft increased each year despite the fact that these graft are known to be more vulnerable to ischemia-reperfusion injuries induced by cold storage preservation (CS). Their use is therefore associated with a greater risk of postoperative dysfunction of the graft. This risk can be reduced by improving preservation quality. The preservation by hypothermic oxygenated perfusion (HOPE) consists of keeping the graft in hypothermia (4 to 12 °C) on an machine perfusion (MP) using a specific solution, saturated with oxygen. In kidney transplantation, the use of MP has been shown to improve graft function as well as graft survival, especially for ECD grafts. In liver transplantation, experimental studies on animal models have demonstrated the superiority of HOPE over CS regarding graft function and survival. These results have been confirmed in humans on small retrospective series. As HOPE is an expensive procedure, obtaining evidence of its effectiveness could result in a reimbursement of the additional cost.

Official Title
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Interest of Oxygenated Hypothermic Perfusion in Preservation of Hepatic Grafts From Expanded Criteria Donors. A Prospective Monocentric Study.

Conditions
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Hepatocellular Injury

Intervention / Treatment
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* Device: Hypothermic oxygenated perfusion (HOPE)
* Other: Conventional cold storage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients older than 18 years Candidates for a first orthotopic liver transplantation, without transplantation of another associated organ (kidney, pancreas, heart, lung, intestine) With cirrhosis whatever its etiology and gravity With or without hepatocarcinoma Having given free, informed and written consent LT made from a whole graft, harvested from a brain-dead donor with ECD criteria, defined as the presence of at least one of the following criteria: Age> 65 years BMI> 30 kg / m2 Duration of hospitalization in intensive care unit> 7 days Natremia> 155 mmol / l AST> 150 IU / ml ALT> 170 IU / ml Occurrence of cardiac arrest before harvesting Macrovacuolar steatosis> 30% on liver histology Exclusion Criteria: History of organ transplantation Transplantation in emergency Transplantation from a living donor, a reduced graft or a graft from a deceased donor by cardiac arrest (DCD) Major persons subject to legal protection (safeguard of justice, guardianship), persons deprived of their liberty

Ages Eligible for Study
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Minimum Age: 18 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypothermic oxygenated perfusion (HOPE)<br>Application of HOPE for 2 hours | Device: Hypothermic oxygenated perfusion (HOPE)<br>* 25 patients: Application of HOPE for 2 hours, perfusion rate 100-150 ml/min, pressure controlled, perfusion pressure < 3 mm Hg, perfusion route portal vein, recirculating system, perfusion volume 2 L, perfusate solution (UWMP®), perfusate temperature 4-12 °C, perfusate oxygenation 40 KPa<br>|
| Active Comparator: Conventional cold storage<br> | Other: Conventional cold storage<br>* 75 patients transplanted in Rennes between 2010 and 2015 with a cold stored grafts, matched (ratio 1: 3) using a propensity score calculated according to some parameters<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the performance of HOPE in the preservation of ECD liver grafts on graft function recovery | Occurrence of early allograft dysfunction and / or primary non function | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the impact of PHO during the conservation of ECD liver grafts on intraoperative morbidity | Number of intraoperative transfusions | Day 1 | 
| Evaluation of the impact of PHO during the conservation of ECD liver grafts on intraoperative morbidity | Incidence of reperfusion syndrome defined as a 30 % decrease of mean arterial pressure, for at least 1 minute, during the 5 minutes following revascularization | Day 1 | 
| Evaluation of the impact of PHO during the conservation of ECD liver grafts on postoperative morbidity |  | Day 7 | 
| Evaluation of graft's survival | Occurrence of a vascular and biliary complication | Month 3 | 
| Number of days of hospitalization (initial stay) after transplantation |  | Postoperative course | 
| Number of days of hospitalization after transplantation |  | Month 3 | 
| Cost of the initial stay |  | Postoperative course | 
| Cost of the hospitalization stay |  | Month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver transplantation, hypothermic machine liver perfusion, extended criteria liver grafts