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

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: Early Allograft Dysfunction; Ischemia-Reperfusion Injury; Primary Non-function; Liver Transplantation (LT)
• Intervention / Treatment: Procedure: Hypothermic Oxygenated Machine Perfusion (HOPE/D-HOPE)

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ivan Vella; Phone Number: +39 3803403369; Email: ivella@ismett.edu
• Study Contact Backup: Name: Monica Rizzo; Phone Number: +39 0912192692; Email: ufficioricerca@ismett.edu

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: Ivan Vella; Phone Number: +39 3803403369; Email: ivella@ismett.edu
    • Contact: Monica Rizzo; Phone Number: +39 0912192692; Email: ufficioricerca@ismett.edu
    • Principal Investigator: Ivan Vella
  • Roma, Italy, 00152
    • Azienda Ospedaliera San Camillo Forlanini

Participation Criteria

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

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: 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	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

• Sponsor: The Mediterranean Institute for Transplantation and Advanced Specialized Therapies

Study record dates

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: liver transplantation; Ischemia-Reperfusion Injury; Early Allograft Dysfunction (EAD); Primary Non-Function (PNF); Liver Graft Viability Assessment
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Reperfusion Injury
• 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