Pyrophosphate Homeostasis and Hepatic Expression of ABCC6.Pyro-TH (Pyro-TH)

Pyrophosphate Homeostasis and Hepatic Expression of ABCC6. Pilot Study in Liver Transplantation

In animals, normal hepatic expression of ABCC6 (ATP-binding transporter cassette, subfamily C, member 6) determines plasma pyrophosphate (PPi) concentration. PPi prevents the formation of hydroxyapatite crystals on tissues by precipitation of calcium and inorganic phosphate (Pi). It is an endogenous compound whose deficiency causes diffuse vascular calcifications in certain rare monogenic diseases, including the elastic pseudoxanthoma caused by the mutation of ABCC6. PPi is produced by enzymatic transformation of extracellular ATP and, in animals, the liver is the main supplier of ATP and PPi (more than 90%). In humans, liver transplantation offers the possibility of correlating the plasma concentration of PPi ([PPi]pl) with hepatic expression of ABCC6. Liver transplantation is performed in the treatment of chronic liver failure (Child B or C) or, in the absence of liver failure, in the treatment of hepatocellular carcinoma. By measuring[PPi]pl before transplantation and after liver function restoration and by measuring ABCC6 in the diseased liver and healthy liver, it is possible to determine whether liver failure is associated with decreased[PPi]pl and decreased liver expression of ABCC6, which is the objective of our pilot study. Its interest is to establish a physiopathological link between the frequent vascular calcifications in obese patients with hepatic steatosis and the production of PPi.

prupose: Look for a deficit in[PPi]pl in patients before the transplant compared to the phase of restoration of liver function

Study Overview

• Status: Completed
• Conditions: Hepatic Failure
• Intervention / Treatment: Other: blood sample

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Antonio IANNELLI, PHD; Phone Number: 33 492 03 60 44; Email: iannelli.a@chu-nice.fr

Study Locations

• France
  • Nice, France, 06000
    • Untiversity Hospital of Nice

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Indication for liver transplantation Age greater than or equal to 18 years Patients affiliated to social security

Exclusion Criteria:

Patient not affiliated to social security Non-consenting patient or unable to understand the protocol and how it works Fulminant Hepatitis

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: cirrhotic patients with chronic liver failure	Other: blood sample; Peripheral venous blood is collected before liver transplantation and after restoration of liver function
Other: cirrhotic patients without chronic liver failure	Other: blood sample; Peripheral venous blood is collected before liver transplantation and after restoration of liver function

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
plasma PPi concentration between before transplantation and liver function restoration in the both arms	24 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2018
• Primary Completion (Actual): October 29, 2020
• Study Completion (Actual): October 29, 2020

Study Registration Dates

• First Submitted: June 22, 2018
• First Submitted That Met QC Criteria: June 22, 2018
• First Posted (Actual): July 3, 2018

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency
• Other Study ID Numbers: 18-AOI-11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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