Impact of machine perfusion of the liver on post-transplant biliary complications: A systematic review

Abstract

Aim: To review the clinical impact of machine perfusion (MP) of the liver on biliary complications post-transplantation, particularly ischaemic-type biliary lesions (ITBL).

Methods: This systematic review was performed in accordance with the Preferred Reporting Systematic Reviews and Meta-Analysis (PRISMA) protocol. The following databases were searched: PubMed, MEDLINE and Scopus. The keyword "liver transplantation" was used in combination with the free term "machine perfusion". Clinical studies reporting results of transplantation of donor human livers following ex situ or in situ MP were analysed. Details relating to donor characteristics, recipients, technique of MP performed and post-operative biliary complications (ITBL, bile leak and anastomotic strictures) were critically analysed.

Results: Fifteen articles were considered to fit the criteria for this review. Ex situ normothermic MP was used in 6 studies, ex situ hypothermic MP in 5 studies and the other 4 studies investigated in situ normothermic regional perfusion (NRP) and controlled oxygenated rewarming. MP techniques which have per se the potential to alleviate ischaemia-reperfusion injury: Such as hypothermic MP and NRP, have also reported lower rates of ITBL. Other biliary complications, such as biliary leak and anastomotic biliary strictures, are reported with similar incidences with all MP techniques. There is currently less clinical evidence available to support normothermic MP as a mitigator of biliary complications following liver transplantation. On the other hand, restoration of organ to full metabolism during normothermic MP allows assessment of hepatobiliary function before transplantation, although universally accepted criteria have yet to be validated.

Conclusion: MP of the liver has the potential to have a positive impact on post-transplant biliary complications, specifically ITBL, and expand extended criteria donor livers utilisation.

Keywords: Donation after circulatory death; Ex situ machine perfusion of the liver; Extended criteria donors; Ischemic-type biliary lesions; Liver transplantation; Non-anastomotic intra-hepatic stricture.

Figure 1

Magnetic resonance cholangiopancreatography images of ischemic-type biliary lesions following liver transplantation. The images show two recipients of livers from donation after circulatory death donors that developed ischemic-type biliary lesions within 60 d following transplantation. Hepatic artery thrombosis and anastomotic biliary strictures were ruled out. A: A typical lesion is seen affecting the bifurcation of the common hepatic bile duct with moderate dilatation of the intrahepatic biliary tree; B: The image shows strictures at the bifurcation of the common hepatic bile duct, diffuse intra-hepatic strictures and a severe dilatation of the intrahepatic biliary tree.

Figure 2

Study flow diagram for systematic review of the literature on the impact of machine perfusion of the liver and post-transplant biliary complications. Following literature search duplicate articles were excluded and the titles screened. The selected abstracts were then read and non-clinical studies or reports unrelated to the aim of the review were excluded.

Figure 3

Diagrammatic summary of the current evidence for the impact of machine perfusion of the liver on post-transplant ischemic-type biliary lesions and future perspectives. The current evidence suggests that ischaemic-type biliary lesions (ITBL) have a multifactorial pathogenesis. These diverse factors lead to injury to the biliary epithelium, peribiliary glands and peribiliary vascular plexus. Currently, there is evidence for the potential benefits of machine perfusion on post-transplant ITBL. The figure summarises those and possible future interventions that could enhance increase these benefits further.