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 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.

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).