The Relationship of Initial Liver Profile and Outcome After Transplantation

The Relationship of Hepatobiliary microRNA Expression Profile and Clinical Outcome in Liver Transplantation

Donation after cardiac death (DCD) livers are increasingly utilised in liver transplantation but concerns exist regarding negative results. Ischemic cholangiopathy (IC) is damage to one or more bile ducts probably caused by inadequate blood flow or a failure of biliary epithelium to regenerate. It typically presents weeks to months after liver transplantation, is often refractory to treatment and can result in a requirement for re-transplantation. Although IC is more common following DCD liver transplantation, it is otherwise very difficult to predict and the underlying pathogenesis is poorly understood. The aim of this study is to correlate microRNA (miRNA) levels and markers of senescence in liver and bile duct biopsies taken during liver transplantation with the incidence of IC following liver transplantation.

Study Overview

• Status: Completed
• Conditions: Liver Failure

Detailed Description

Study population

Tissue from all deceased adult liver transplant grafts will be collected. The test samples will be selected from procedures were the liver transplant recipient has developed IC. The control samples will include tissues from procedures were the transplant recipient had an uncomplicated outcome. There will be matching of test samples and control samples based on a range of clinical factors.

Consent

Standard consent for organ donation documentation has a general consent to research section. Due to the small risk of damage to blood vessels when taking samples the liver transplant recipient will also be consented for these procedures to take place.

Tissue sampling

Liver and bile duct samples from each graft will be obtained at various different time points during liver transplant procedures.

Processing of specimens

Following removal of the specimens, samples will be divided then added to RNAlater (Life Technologies, Paisley, UK), 10% formaldehyde or will be snap frozen. At a later time point samples will be analysed.

Definition of ischemic cholangiopathy

IC will be defined as strictures, dilatations, or irregularities of the intra- or extrahepatic bile ducts of the liver graft. Isolated strictures at the bile duct anastomosis will be excluded. The diagnosis will be based on at least one adequate imaging study of the biliary tree, after exclusion of hepatic artery thrombosis by Doppler ultrasound, computed tomography or conventional angiography.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

Study Locations

• United Kingdom
  • Midlothian
    • Edinburgh, Midlothian, United Kingdom, EH16 4SA
      • Royal Infirmary of Edinburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Liver transplantation group

Description

Inclusion Criteria:

• All deceased adult liver transplant donors (>16 years of age) whose livers are being utilised for transplantation in the Scottish Liver Transplant Unit in the Royal Infirmary of Edinburgh

Exclusion Criteria:

• Paediatric liver transplant donors (<16 years of age).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Liver transplantation group; Participants will include all deceased adult liver transplant donors (>16 years of age) whose livers are being utilised for transplantation in the Scottish Liver Transplant Unit in the Royal Infirmary of Edinburgh. Exclusion criteria will include paediatric liver transplant donors (<16 years of age).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in hepatobiliary miRNA expression during liver transplantation in liver grafts that develop ischemic cholangiopathy following liver transplantation	Assessed by sequencing of liver and bile duct samples taken during different stages of liver transplantation and correlation with clinical outcomes	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in hepatobiliary senescence during liver transplantation in liver grafts that develop ischemic cholangiopathy following liver transplantation	Assessed by senescence markers in liver and bile duct samples taken during different stages of liver transplantation and correlation with clinical outcomes	12 months

Collaborators and Investigators

• Sponsor: University of Edinburgh
• Collaborators: NHS Lothian
• Investigators: Principal Investigator: Ewen Harrison, University of Edinburgh

Publications and helpful links

General Publications

• O'Neill S, Roebuck A, Khoo E, Wigmore SJ, Harrison EM. A meta-analysis and meta-regression of outcomes including biliary complications in donation after cardiac death liver transplantation. Transpl Int. 2014 Nov;27(11):1159-74. doi: 10.1111/tri.12403.

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2014
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: November 24, 2014
• First Submitted That Met QC Criteria: December 1, 2014
• First Posted (Estimated): December 4, 2014

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 16, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Liver Transplantation
• Additional Relevant MeSH Terms: Digestive System Diseases; Hepatic Insufficiency; Liver Diseases; Liver Failure
• Other Study ID Numbers: 2014/097

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED