Tissue Analysis of Liver Grafts as a Predictor of Transplant Outcome.

Tissue Analysis (Histological, Ultrastructural and Molecular) of Liver Grafts as a Predictor of Transplant Outcome.

Despite the good clinical results in terms of outcome with the application of HOPE prior to liver transplantation, very little is still known about the phenotypic and molecular changes that occur during perfusion/preservation during HOPE, particularly with regard to endothelial trophism and activation. Delving into these aspects would be very useful to allow personalised perfusion treatments in the future, thus improving the outcome of transplantation.

Study Overview

• Status: Recruiting
• Conditions: Rejection; Transplant, Liver; Hepatic Transplantation
• Intervention / Treatment: Diagnostic test: histochemical and immunohistochemical analysis; Diagnostic test: RT-PCR

Detailed Description

The primary aim of the study is the identification of specific 'endothelial signatures' (markers on tissue with immunohistochemistry and gene expression with RT-PCR) in liver grafts after HOPE treatment, predictive of transplant outcome. Interventional study without drug, including two cohorts of patients: (1) liver donors, on whom an allocation biopsy for organ quality will be performed (as standard of care); (2) liver recipients (from donors in cohort 1) on whom a study-specific biopsy will be performed as soon as the transplant has taken place (after vascular anastomoses with organ revascularisation). The study-specific biopsy constitutes the intervention of the study; patients will be treated according to the judgement of the physician and the information reported in the Technical Data Sheet of each product of any concomitant therapies administered according to clinical practice.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Francecso Vasuri, MD; Phone Number: 0512143761; Email: francesco.vasuri2@unibo.it
• Study Contact Backup: Name: Deborah Malvi, MD; Phone Number: 0512143761; Email: deborah.malvi@aosp.bo.it

Study Locations

• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna
    • Contact: Francesco Vasuri, MD; Phone Number: 0512143761; Email: francesco.vasuri2@unibo.it
    • Principal Investigator: Francesco Vasuri, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• For Donors:

Availability of enough tissue for histological, immunohistochemical and RT-PCR analysis.

• HOPE performed on the liver graft prior to transplantation.
• For Recipients:
• Availability of enough tissue for histological, immunohistochemical and RT-PCR analysis.
• Age greater than/equal to 18 years.

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Organ donors; organ donors (legally deceased, brain death or cardiac death)	Diagnostic test: histochemical and immunohistochemical analysis; 2 µm sections will be cut from the paraffin blocks for histochemical and immunohistochemical (IHC) investigations. IHC will be performed with an automated stainer (Ventana/Roche®, Ventana Medical Systems, USA) for the endothelial markers CD34, ERG, Nestin and Caveolin-1; Diagnostic test: RT-PCR; Custom RT-PCR analyses will be performed manually for the transcripts (mRNA) of the ERG, Nestin, VEGFR and other genes, at the Pathology Anatomy lab hall. 18 (Prof. D'Errico). Total RNA will be extracted from the paraffin blocks with the RecoverAll™ Total Nucleic Acid Isolation kit (Invitrogen). Reverse Transcriptase will be performed with the High Capacity Reverse Transcription kit (Life Technologies), using the specific primers. Real-Time PCR will be performed with the CFX Connect Real-Time PCR Identification System (BioRad).
Other: Organ recipients	Diagnostic test: histochemical and immunohistochemical analysis; 2 µm sections will be cut from the paraffin blocks for histochemical and immunohistochemical (IHC) investigations. IHC will be performed with an automated stainer (Ventana/Roche®, Ventana Medical Systems, USA) for the endothelial markers CD34, ERG, Nestin and Caveolin-1; Diagnostic test: RT-PCR; Custom RT-PCR analyses will be performed manually for the transcripts (mRNA) of the ERG, Nestin, VEGFR and other genes, at the Pathology Anatomy lab hall. 18 (Prof. D'Errico). Total RNA will be extracted from the paraffin blocks with the RecoverAll™ Total Nucleic Acid Isolation kit (Invitrogen). Reverse Transcriptase will be performed with the High Capacity Reverse Transcription kit (Life Technologies), using the specific primers. Real-Time PCR will be performed with the CFX Connect Real-Time PCR Identification System (BioRad).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of specific '"endothelial signatures"	Main outcomes to assess the outcome of transplantation will be the percentage of early (PNF and EAD, within 1 week after transplantation) and late (rejection and complications) complications, as well as mortality among recipients within 24 months.	Within 24 months

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Francesco Vasuri, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: December 1, 2024
• First Submitted That Met QC Criteria: December 1, 2024
• First Posted (Estimated): December 5, 2024

Study Record Updates

• Last Update Posted (Estimated): December 5, 2024
• Last Update Submitted That Met QC Criteria: December 1, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Transplant; Liver
• Other Study ID Numbers: donorHOPE_2022; RC-2022-2773274 (Other Grant/Funding Number: Ministero della Salute)

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