Liver Failure
Conditions
Keywords
Liver Transplantation
Brief summary
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.
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.
Interventions
None listed
Sponsors
NHS Lothian
University of Edinburgh
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in hepatobiliary miRNA expression during liver transplantation in liver grafts that develop ischemic cholangiopathy following liver transplantation | 12 months | Assessed by sequencing of liver and bile duct samples taken during different stages of liver transplantation and correlation with clinical outcomes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in hepatobiliary senescence during liver transplantation in liver grafts that develop ischemic cholangiopathy following liver transplantation | 12 months | Assessed by senescence markers in liver and bile duct samples taken during different stages of liver transplantation and correlation with clinical outcomes |
Countries
United Kingdom
Outcome results
None listed