MicroRNA Profile As a Biomarker of Liver Damage in Different Types of Liver Donors.

NCT06611046 | Completed

• 1 other identifier: PR(AG)46/2019
• Study Type: observational
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to analyze the expression of liver-derived miRNAs in different types of liver donors to gain in depth knowledge about distinctive physiologic features within donors and find potential biomarkers for graft quality assessment. The main questions it aims to answer are: Is there a distinctive miRNA profile between donors after brain-stem death and donors after circulatory death? Is heparinase I treatment necessary to overcome miRNA quantification interference in heparinized liver donor samples ? Researchers will compare miRNA expression in donors after brain-stem death and donors after circulatory death with I) a subgroup of donors with unusable grafts due to significant steatosis, 2) and with a subgroup of healthy controls undergoing elective cholecystectomy to set the reference miRNA profiles in extreme conditions.

Conditions

MicroRNA Profile; Liver Transplant; Organ Donor

Keywords

microRNA; Liver donors; Liver transplant; heparinase

Outcome Measures

Primary Outcomes (1)

• miRNA expression profile in different types of liver donors.

  Compare the miRNA expression profile (miR-122 and miR-148a, miR-222, miR-22 and miR-155) from death brain donors and circulatory death donors in liver biopsies, serum and perfusion solution

  Data collection from regional donors in a period of two years based on donor availability and main investigator (data collector) availability. The samples were collected during organ procurement which entails over 4 to 6 hours in each donor.

Study Arms (4)

Death brain donors (DBD)

Liver grafts from brain death donors suffer systemic haemodynamic, inflammatory and endocrine changes during donor maintenance due to brain-stem activity cessation.

Other: organ donor

Donors after circulatory death (DCD)

Circulatory death donors do not suffer the physiologic features from brain death, almost mirroring a living donation. However, after withdrawal of life-sustaining measures these grafts suffer injury from severe ischemia.

Other: organ donor

Discarded DBD (dDBD)

Liver grafts from brain death donors that were unusable due to moderate to severe steatosis. Fatty livers are vulnerable to preservation injury resulting in a higher rate of primary non-function, early allograft dysfunction and post-transplant vascular and biliary complications

Other: organ donor

Control group

Serum samples from healthy patients who underwent elective cholecystectomy due to symptomatic gallstones were collected before incision. The patients included shared similar characteristics according to the centre living liver donor policy: 18 to 60-year-old, normal liver function and no steatosis in ultrasound.

Other: organ donor

Interventions

organ donor OTHER

Observational study with sample collection of serum, liver tissue and perfusate fluid from liver donors. No specific interventions were done to the donors as part of the study. The samples were analyzed for specific microNA expression by RT-qPCR. \*Control group: only serum samples were collected from this group.

Control group; Death brain donors (DBD); Discarded DBD (dDBD); Donors after circulatory death (DCD)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Fourteen combined perfusates, liver biopsies and serum samples were collected prospectively from brain death donors (DBD, n=14) and donors after circulatory death (DCD, n=14). Three combined perfusates, liver biopsies and serum samples were collected prospectively from brain death donors discarded for transplantation due to significant steatosis (DBDd, n=3). Seven serum samples were collected prospectively from healthy controls undergoing elective cholecystectomy (Control, n=7). Single centre study with samples collected at Vall d'Hebron University Hospital, Spain, between October 2019 and May 2021.

You may qualify if:

• Adult deceased liver donors

You may not qualify if:

• Pediatric donors (less than18 year-old)
• Donors for re-transplantation cases
• Donors who underwent split or partition liver technique to obtain two small grafts for two recipients (adult and pediatric).
• II) Discarded DBD grafts:
• \- Unusable grafts for transplantation due to moderate (30% to 60%) or severe (more than 60%) steatosis in liver biopsies.
• Unusable grafts discarded for other reasons.
• Pediatric donors (less than18 year-old)
• Donors for re-transplantation cases
• Donors who underwent split or partition liver technique to obtain two small grafts for two recipients (adult and pediatric).
• III) Control group:
• \- Patients with preoperative deranged liver function tests.

Sponsors & Collaborators

• Mar Dalmau: lead
• Vall Hebron Insitut Recerca: collaborator

Study Sites (1)

Vall d Hebron University Hospital

Barcelona, Barcelona, 08035, Spain

Location

Related Publications (1)

• Dalmau M, Charco R, Bilbao I, Dopazo C, Caralt M, Molino JA, Gomez-Gavara C. Heparinase I treatment to overcome RNA quantification interference in heparinized liver donor samples: One size fits all? PLoS One. 2025 May 12;20(5):e0322899. doi: 10.1371/journal.pone.0322899. eCollection 2025.

  PMID: 40354476 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

* Serum extracted from blood samples * Liver biopsies * Preservation solution fluid

Study Officials

• Ramon Charco, MD, PhD

  Chief of HPB surgery and Transplant Department in Vall d Hebron University Hospital

  STUDY DIRECTOR

• Concepción Gómez-Gavara, MD, PhD

  HPB surgery and Liver Transplant consultant in Vall d Hebron University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Specialist in General Surgery and Digestive System

Study Record Dates

• First Submitted: September 19, 2024
• First Posted: September 24, 2024
• Study Start: October 2, 2019
• Primary Completion: July 27, 2021
• Study Completion: September 1, 2024
• Last Updated: September 24, 2024

Record last verified: 2024-09

Locations

ES (1)