New Biomarkers for Organ Viability Assessment During Hypothermic Machine Perfusion in Liver Transplantation: the Role of Extemporaneous Histological Examination. (LOVE)

June 23, 2026 updated by: The Mediterranean Institute for Transplantation and Advanced Specialized Therapies

Liver transplantation is a life-saving treatment for patients with severe liver disease. Because of the shortage of donor organs, transplant centers increasingly use donor livers that may be more vulnerable to injury and dysfunction. To improve the quality of these organs before transplantation, many centers use hypothermic oxygenated machine perfusion (HOPE or D-HOPE), a technique that preserves the liver under cold, oxygenated conditions. However, there are currently no widely accepted methods to determine whether a liver is functioning well enough during this preservation process.

The purpose of this study is to investigate whether changes observed in liver tissue during hypothermic machine perfusion can help predict how well the transplanted liver will function after surgery. The study will compare liver biopsy samples collected before and after one hour of perfusion and will analyze biological markers released into the perfusion fluid, including markers of mitochondrial injury and inflammation.

The main question this study aims to answer is whether histological changes occurring during hypothermic perfusion, alone or in combination with biochemical biomarkers, can accurately predict liver graft viability and post-transplant outcomes. Researchers will also evaluate whether these data can be used to develop an artificial intelligence-based model to support clinical decision-making during organ preservation.

A total of 150 adult liver transplant recipients receiving donor livers treated with HOPE or D-HOPE will be enrolled at three Italian liver transplant centers. Participants will be followed for 90 days after transplantation to assess liver graft function, graft survival, patient survival, and post-transplant complications.

The results of this study may improve the assessment of donor liver quality before transplantation and help clinicians make more informed decisions about organ use, ultimately increasing the safety and effectiveness of liver transplantation.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Milan, Italy, 20162
        • Asst Grande Ospedale Metropolitano Niguarda
      • Palermo, Italy, 90127
        • IRCCS ISMETT - Istituto Mediterraneo per i Trapianti e le Terapie ad Alta Specializzazione,
        • Contact:
        • Contact:
        • Principal Investigator:
          • Ivan Vella
      • Roma, Italy, 00152
        • Azienda Ospedaliera San Camillo Forlanini

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adult liver transplant recipients (≥18 years of age).
  2. Donor liver grafts from either Donation after Brain Death (DBD) or Donation after Circulatory Death (DCD).
  3. Grafts undergoing hypothermic oxygenated perfusion (HOPE) (HOPE or D-HOPE) for a minimum duration of 1 hour prior to transplantation.
  4. Availability of two wedge liver biopsy samples: one pre perfusion and one post-perfusion.
  5. Grafts preserved using standard cold storage protocols and transported in ice-cold Servator C™ solution.
  6. Informed consent obtained from the recipient (or legal representative, where applicable) for the use of clinical and histological data for research purposes.

Exclusion Criteria:

  1. Inadequate or fragmented biopsy samples, preventing proper histological evaluation.
  2. Biopsy samples showing histological features of pre-existing chronic liver disease (e.g., cirrhosis, autoimmune hepatitis, chronic viral hepatitis).
  3. Liver grafts subjected to normothermic perfusion or other non hypothermic perfusion techniques.
  4. Organs undergoing experimental or non-standard perfusion protocols.
  5. Grafts from donors <18 years of age.
  6. Recipient refusal or inability to provide informed consent.
  7. Technical failure during perfusion (e.g., incomplete perfusion due to device malfunction or vascular anomalies).
  8. Known malignancy in the donor with potential liver involvement, excluding donors with small incidentalomas as per standard guidelines.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HOPE/D-HOPE Liver Transplant Recipients
Adult liver transplant recipients receiving donor liver grafts preserved with hypothermic oxygenated machine perfusion (HOPE or D-HOPE) prior to transplantation. Liver biopsies and perfusate samples are collected before and during perfusion for histological and biomarker analyses, and participants are followed for 90 days after transplantation.
Procedure: Hypothermic Oxygenated Machine Perfusion (HOPE/D-HOPE)
Standard-of-care hypothermic oxygenated machine perfusion of donor liver grafts before transplantation, with collection of biopsies and perfusate samples for research analyses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Graft Survival
Time Frame: 90 days after liver transplantation
Graft survival defined as the absence of Early Allograft Dysfunction (EAD) or Primary Non-Function (PNF) following liver transplantation. Histological changes observed between pre-perfusion and post-perfusion liver biopsies will be evaluated for their association with graft outcomes.
90 days after liver transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Mediterranean Institute for Transplantation and Advanced Specialized Therapies

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

June 1, 2029

Study Registration Dates

First Submitted

June 23, 2026

First Submitted That Met QC Criteria

June 23, 2026

First Posted (Actual)

June 29, 2026

Study Record Updates

Last Update Posted (Actual)

June 29, 2026

Last Update Submitted That Met QC Criteria

June 23, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRRB/13/26

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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