Aetiology and risk factors of ischaemic cholangiopathy after liver transplantation

Abstract

Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasing number of procured organs after circulatory death. Ischaemic cholangiopathy (IC) is a set of disorders characterized by multiple diffuse strictures affecting the graft biliary system in the absence of hepatic artery thrombosis or stenosis. It commonly presents with cholestasis and cholangitis resulting in higher readmission rates, longer length of stay, repeated therapeutic interventions, and eventually re-transplantation with consequent effects on the patient's quality of life and increased health care costs. The pathogenesis of IC is unclear and exhibits a higher prevalence with prolonged ischaemia time, donation after circulatory death (DCD), rejection, and cytomegalovirus infection. The majority of IC occurs within 12 mo after LT. Prolonged warm ischaemic times predispose to a profound injury with a subsequently higher prevalence of IC. Biliary complications and IC rates are between 16% and 29% in DCD grafts compared to between 3% and 17% in donation after brain death (DBD) grafts. The majority of ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts following transplantation. However, there are many other risk factors for IC that should be considered. The benefits of DCD in expanding the donor pool are hindered by the higher incidence of IC with increased rates of re-transplantation. Careful donor selection and procurement might help to optimize the utilization of DCD grafts.

Keywords: Biliary complications; Cold ischaemia time; Donation after circulatory death; Ischaemic cholangiopathy; Orthotopic liver transplantation; Reperfusion injury.

Figure 1

Magnetic resonance cholangiopancreatography images of 60-year-old patient who received a donation after circulatory death liver graft. A: The patient developed ischaemic type intra-hepatic biliary strictures 8-mo post-transplant, confirmed to be of ischemic origin by liver biopsy; B: Dilated intra-hepatic ducts proximal to intra-hepatic biliary strictures.

Figure 2

Cold and warm liver ischaemia-reperfusion leading to ischaemic cholangiopathy following liver transplantation. Drawing illustrates the pathogenesis of IC after OLT[12]. ROS: Reactive oxygen species; MPT: Mitochondrial permeability transition; ATP: Adenosine triphosphate; DCD: Donation after circulatory death; IC: Ischaemic cholangiopathy; OLT: Orthotopic liver transplantation.

Figure 3

Ischaemic cholangiopathy for donation after circulatory death and donation after brain death liver recipients. A meta-analysis: Eight studies reported IC rates for both DCD and DBD cohorts. These studies demonstrated an IC rate of 16% (8%-38%) for DCD recipients compared with 3% (0%-8%) of DBD recipients. DCD recipients had a 10.8 times increased odds of IC (95%CI: 4.8-24.2)[16]. DCD: Donation after circulatory death; DBD: Donation after brain death; IC: Ischaemic cholangiopathy.