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

NCT07674394 | Not Yet Recruiting

• 1 other identifier: IRRB/13/26
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Liver Transplantation (LT); Early Allograft Dysfunction; Primary Non-function; Ischemia-Reperfusion Injury

Keywords

liver transplantation; Early Allograft Dysfunction (EAD); Primary Non-Function (PNF); Ischemia-Reperfusion Injury; Liver Graft Viability Assessment

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

HOPE/D-HOPE Liver Transplant Recipients

EXPERIMENTAL

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)

Interventions

Hypothermic Oxygenated Machine Perfusion (HOPE/D-HOPE) PROCEDURE

Standard-of-care hypothermic oxygenated machine perfusion of donor liver grafts before transplantation, with collection of biopsies and perfusate samples for research analyses.

HOPE/D-HOPE Liver Transplant Recipients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (3)

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

IRCCS ISMETT - Istituto Mediterraneo per i Trapianti e le Terapie ad Alta Specializzazione,

Palermo, 90127, Italy

Location

Azienda Ospedaliera San Camillo Forlanini

Roma, 00152, Italy

Location

MeSH Terms

Conditions

Reperfusion Injury

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Ivan Vella

CONTACT

+39 3803403369; ivella@ismett.edu

Monica Rizzo

CONTACT

+39 0912192692; ufficioricerca@ismett.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2026
• First Posted: June 29, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: June 29, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3)