APHP Plateform of Normothermic Perfusion for Rehabilitation of Hepatic Grafts

Study Overview
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Brief Summary
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This study aimed to evaluate fatty liver grafts, considered as unsuitable for upfront liver transplantation, by using normothermic perfusion. Grafts have to be allocated to one of 3 liver transplantation centres of Paris. After evidence of viability while on perfusion, these grafts will be transplanted to recipients with an estimated waiting time > 6 months.

Detailed Description
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In this study, the coordinator investigator proposes to build a platform for perfusing in normothermic conditions all grafts with histologically proven macrosteatosis ≥ 30% that will be considered as unsuitable for upfront LT. These grafts have to be alloacted to one of the 3 liver transplantation centers of Assistance Publique des Hôpitaux de Paris. Eligible grafts (macrosteatosis ≥ 30%, no severe fibrosis or cirrhosis) will be shipped to the platform for normothermic perfusion. Perfusion will be started provided that cold ischemia time do not exceed 8 hours. Parameters of grafts viability (lactates, bile production, flow) will be monitored. After a minimum of 4 hours of normothermic perfusion (not exceeding 16 hours), grafts fulfilling strict criteria (homogeneous aspect of the liver without any necrotic regions, lactates < 2.5 mmol/l and continuous production of bile with at least one of the following criteria: pH of perfusate > 7.3, arterial flow > 150 ml/min and portal flow > 500 ml/min, homogeneous perfusion of the graft) will be considered suitable for transplantation. Recipient will be transferred to the operating room, and first phase of LT (i.e, laparotomy and total hepatectomy) will be started. Simultaneously, grafts will be shipped to the center of initial allocation. Perfusion will be pursued during the transport from the platform to the recipient. Recipients (≥18 years and ≤ 70 years) have to be enlisted for LT with an estimated waiting time > 6 months (i.e., MELD score < 25) and who signed an informed consent.

Official Title
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APHP Plateform for Assessement of Hepatic Grafts Initialy Discarded by Normothermic Perfusion

Conditions
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Liver Diseases

Intervention / Treatment
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* Procedure: Liver transplantation of a graft after assessment by normothermic perfusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients enlisted for liver transplantation for liver disease or HCC (AFP score≤ 2); Ongoing cotraception in women of reproductive age ; Patient with social security ; informed signed consent Exclusion criteria: Extra-hepatic tumor disease; Re-transplantation ; Pregnancy or brest-feeding; Patients participting in another study; Patients under psychiatric treatment; Patients under tutorship or curatorship

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

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
Intervention Model: Single Group Assignment
Interventional Model Description: Liver transplantation of a graft after assessment by normothermic perfusion
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normothermic perfusion of a graft<br> | Procedure: Liver transplantation of a graft after assessment by normothermic perfusion<br>* Liver transplantation of a graft after assessment by normothermic perfusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the proportion of grafts that can be transplanted after evaluation by normothermic perfusion (Hypothesis 50%) with a 3-year graft survival ≥ 90% | Graft survival | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of hepatic grafts allocated to the 3 transplant centres of Paris and considered as initially not transplantable during the study period | Proportion of hepatic grafts allocated to the 3 transplant centres of Paris and considered as initially not transplantable during the study period | 36 months | 
| Proportion of fatty grafts allocated to the 3 transplant centres of Paris and considered as initially not transplantable during the study period eligible for normothermic perfusion | Proportion of fatty grafts allocated to the 3 transplant centres of Paris and considered as initially not transplantable during the study period eligible for normothermic perfusion | 36 months | 
| Proportion of grafts perfused | Proportion of grafts perfused | 36 months | 
| Proportion of grafts that were transplanted after perfusion | Proportion of grafts that were transplanted after perfusion | 36 months | 
| Time interval until liver function recovery while on normothermic perfusion (according to viability criteria defined above) | Time interval until liver function recovery while on normothermic perfusion (according to viability criteria defined above) | 15 hours | 
| Proportions of grafts transplanted after normotheric perfusion wthout early allograft dysfunction (according to Olthoff definition) | Proportions of grafts transplanted after normotheric perfusion wthout early allograft dysfunction (according to Olthoff definition) | one month | 
| Time interval until liver function recovery after transplantation | Time interval until liver function recovery after transplantation | one day | 
| One-month overall survival (without retransplantation or graft dysfunction) | One-month overall survival (without retransplantation or graft dysfunction) | one month | 
| One -year graft survival | One -year graft survival | one year | 
| Comparison of 3-months graft survival with a control group of graft considered as initially transplantable | Comparison of 3-months graft survival with a control group of graft considered as initially transplantable | 3 months | 
| Waiting time between the two groups |  | 36 months | 
| Incidence of biliary stenosis (anastomotic or non anastomotic) defined by cholangio MRI at one year | Incidence of biliary stenosis (anastomotic or non anastomotic) defined by cholangio MRI at one year | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Steatotic liver graft, Liver transplantation, Normothermic perfusion