Evaluation of Liver Grafts With FibroScan® Before Organ Retrieval in Patients With Brain Death (FIBROSCAME)

According to the French Biomedicine Agency annual report on retrieval activities and transplants, 1,164 liver transplants were performed in 2011 and 1,161 in 2012. If the amount of brain death donors and retrieved liver grafts appears relatively stable, it remains clearly insufficient compared to the increasing number of patients on the waiting list for liver transplantation (2,462 in 2011). The median time on the waiting list before liver transplantation which was established from the cohort of patients registered between 2007 and 2011 (excluding patients registered for emergency transplantation and for living related-donor transplantation) increased significantly from 4.4 months between 2007 and 2009 to 6.6 months between 2010 and 2011. In order to compensate for the lack of liver grafts, donors acceptance criteria were broadened. For example, alternative transplantation lists were created with liver grafts coming from so-called "marginal" donors. However, despite these efforts, livers were retrieved on only two out of three brain death donors, i.e. in 1,572 and 1,589 organ donors in 2011 and 2012, respectively. This is unfortunately not enough to meet the increasing needs in liver grafts and a growing number of patients wait each year for transplant. Strategic lines of improvement were defined in order to meet the "2012-2016 transplant perspective" which targets 5,700 transplants carried out in 2015 (+5% every year, all transplants included, with 5,023 transplants in 2012).

According to the last consensus conference on liver transplantation of the HAS (French High Authority of Health) the assessment of the degree of macrovacuolar and microvacuolar steatosis determines the possibility to retrieve the graft or not. Liver steatosis consists in an accumulation of fatty droplets in hepatocytes. Its prevalence is high, ranging from 16% to 31% in the general population, and increases up to 46% in heavy drinkers and to 50-80% in the obese population. Steatosis results mostly from alcohol consumption and from metabolic syndrome (obesity, type 2 diabetes, hypertriglyceridemia) called non-alcoholic fatty liver disease (NAFLD), and is more rarely secondary to viral hepatitis or exposure to certain medications. NAFLD involves up to 30% of the population in Western countries and its prevalence is increasing. NAFLD may lead to asymptomatic steatosis, but also to steatohepatitis or advanced fibrosis including cirrhosis and its complications Accordingly, the improvement of liver grafts selection based on objective quantitative criteria which takes into account the degree of liver steatosis appears crucial to increase the number of hepatic transplants.

Study Overview

• Status: Completed
• Conditions: Liver Transplantation; Brain Death; Tissue and Organ Harvesting
• Intervention / Treatment: Procedure: Fibroscan

Detailed Description

Medical procedure: Fibroscan® based on vibration control transient elastography (VCTETM) with evaluation of controlled attenuation parameter (CAP™) by ultrasounds (Echosens, Paris, France).

• Study Type: Interventional
• Enrollment (Actual): 740
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80054
    • University Hospital
  • Angers, France, 49100
    • University Hospital
  • Besançon, France, 25030
    • University Hospital
  • Bordeaux, France, 33000
    • University Hospital
  • Brest, France, 29200
    • University Hospital
  • Caen, France, 14033
    • University Hospital
  • Clermont Ferrand, France, 63100
    • Estaing University Hospital
  • Creteil, France, 94010
    • AP-HP Henri Mondor
  • Grenoble, France, 38043
    • University Hospital
  • Lille, France, 59037
    • University Hospital
  • Limoges, France, 87042
    • University Hospital
  • Lyon, France, 69004
    • Croix Rousse Hospital
  • Nice, France, 06000
    • Nice University Hospital
  • Paris, France, 84270
    • AP-HP Kremlin Bicêtre
  • Poitiers, France, 86021
    • University Hospital
  • Reims, France, 51100
    • Univesity Hospital
  • Rennes, France, 35033
    • University Hospital
  • Tours, France, 37044
    • University Hospital
  • Vandoeuvre-les-nancy, France, 54500
    • University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients older than 18 years with recognized clinical brain death confirmed by clinical examination, who are considered for organ retrieval and clinically stable to achieve the retrieval procedure

Exclusion Criteria:

• Personal objection to organ retrieval and clinical research expressed during lifetime and registered in the Registre National des Refus (French registration of all refusals to organ donation)
• Family objection to liver retrieval after donor's death
• Ongoing pregnancy when brain death is declared
• For FT and ST measurements included in the panel FibroMaxTM, 4 exclusion criteria are defined specifically (Acute hepatitis or cytolysis with ALT higher than 622 IU/L, acute or chronic hemolysis, extrahepatic cholestasis, sepsis)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fibroscan; All included patients will undergo a Fibroscan (either Fibroscan Touch model or 402 model which enable CAPTM data extraction) once all eligibility criteria have been checked. Liver recipients will be followed up during one year. Biological and medical data used by all transplant sites for the follow-up of transplant patient will be collected	Procedure: Fibroscan; All included patients will undergo a Fibroscan (either Fibroscan Touch model or 402 model which enable CAPTM data extraction) once all eligibility criteria have been checked.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Controlled Attenuation Parameter™ (CAP™) measurement	Evaluation of the diagnostic accuracy of the CAP™ measured with Fibroscan® to objectively reflect the degree of liver steatosis, a parameter which can be used as an aid in selecting liver grafts before retrieval in donors with brain death (DBD).	1 Day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver Stiffness (LS) measurement	Evaluation of the diagnostic accuracy of LS measured with Fibroscan® to objectively reflect the degree of fibrosis and steatosis, a parameter which can be used as an aid in selecting liver grafts before retrieval in DBD	1 Day
Controlled Attenuation Parameter™ (CAP™) measurement	Determination of the prognostic value of CAP™ in terms of survival of liver grafts at one week after transplantation	1 week
Liver Stiffness (LS) measurement	Determination of the prognostic value of LS in terms of survival of liver grafts at one week after transplantation	1 week
Liver Stiffness (LS) measurement	Determination of the prognostic value of LS in terms of survival of liver grafts at one month after transplantation	1 month
Controlled Attenuation Parameter™ (CAP™) measurement	Determination of the prognostic value of CAP™ in terms of survival of liver grafts at one month after transplantation	1 month
Liver Stiffness (LS) measurement	Determination of the prognostic value of LS in terms of survival of liver grafts at one week, one month and one year after transplantation	1 year
Controlled Attenuation Parameter™ (CAP™) measurement	Determination of the prognostic value of CAP™ in terms of survival of liver grafts at one week, one month and one year after transplantation	1 year
Fibrosis measurement	evaluate the diagnostic a accuracy of FibroTest in selecting liver grafts before retrieval in DBD by comparing with 1) histological data obtained with liver biopsy (degree of steatosis, degree of fibrosis) and with 2) CAPTM/LS	1 Day
Steatosis measurement	evaluate the diagnostic a accuracy of SteatoTest in selecting liver grafts before retrieval in DBD by comparing with 1) histological data obtained with liver biopsy (degree of steatosis, degree of fibrosis) and with 2) CAPTM/LS	1 Day
Fibrosis measurement	Determination of the short-term prognostic values of FibroTest in terms of survival of liver grafts at one month after transplantation	1 month
Steatosis measurement	Determination of the short-term prognostic values of SteatoTest in terms of survival of liver grafts at one month after transplantation	1 month
Fibrosis measurement	Determination of the short-term prognostic values of FibroTest in terms of survival of liver grafts at one year after transplantation	1 year
Steatosis measurement	Determination of the short-term prognostic values of SteatoTest in terms of survival of liver grafts at one year after transplantation	1 year

Collaborators and Investigators

• Sponsor: University Hospital, Limoges
• Investigators: Principal Investigator: Nicolas PICHON, MD, University Hospital, Limoges

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): November 9, 2017
• Study Completion (Actual): November 9, 2018

Study Registration Dates

• First Submitted: May 13, 2015
• First Submitted That Met QC Criteria: May 28, 2015
• First Posted (Estimate): June 2, 2015

Study Record Updates

• Last Update Posted (Actual): October 24, 2019
• Last Update Submitted That Met QC Criteria: October 23, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Brain Death; Tissue and Organ Harvesting; Liver graft; FibroScan®
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Unconsciousness; Consciousness Disorders; Coma; Death; Brain Death
• Other Study ID Numbers: I12033 FIBROSCAME