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World J Gastroenterol. May 28, 2023; 29(20): 3066-3083
Published online May 28, 2023. doi: 10.3748/wjg.v29.i20.3066
Machine perfusion and the prevention of ischemic type biliary lesions following liver transplant: What is the evidence?
Manuel Durán, Rafael Calleja, Angus Hann, George Clarke, Ruben Ciria, Anisa Nutu, Rebeca Sanabria-Mateos, María Dolores Ayllón, Pedro López-Cillero, Hynek Mergental, Javier Briceño, M Thamara P R Perera
Manuel Durán, Rafael Calleja, Ruben Ciria, María Dolores Ayllón, Pedro López-Cillero, Javier Briceño, Department of Liver Transplantation, Reina Sofía University Hospital, Córdoba 14004, Spain
Angus Hann, George Clarke, Anisa Nutu, Rebeca Sanabria-Mateos, Hynek Mergental, M Thamara P R Perera, The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
Angus Hann, George Clarke, Hynek Mergental, M Thamara P R Perera, Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TH, United Kingdom
Author contributions: Perera MTPR and Hann A contributed to the conceptualization; Durán M, Hann A, Calleja R, and Clarke G performed the literature review; Durán M, Hann A, Clarke G, and Calleja R wrote the original draft; Perera MTPR, Hann A, Briceño J, Calleja R, Nutu A, Ayllón MD, López-Cillero P, Sanabria-Mateos R, and Mergental H wrote the review and performed the editing; All authors have read and agreed to the published version of the manuscript.
Conflict-of-interest statement: The funding provided for normothermic machine perfusion consumables generously donated by the Ann Fox Foundation, under the umbrella of University Hospital Birmingham Charities.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: M Thamara P R Perera, FEBS, FRCS, MBBS, MD, MS, Chairman, Professor, Surgeon, The Liver Unit, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham B15 2TH, United Kingdom. thamara.perera@uhb.nhs.uk
Received: January 26, 2023
Peer-review started: January 26, 2023
First decision: February 16, 2023
Revised: March 1, 2023
Accepted: April 28, 2023
Article in press: April 28, 2023
Published online: May 28, 2023
Abstract

The widespread uptake of different machine perfusion (MP) strategies for liver transplant has been driven by an effort to minimize graft injury. Damage to the cholangiocytes during the liver donation, preservation, or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage. This problem continues to trouble clinicians, and may have catastrophic consequences for the graft and patient. Ischemic injury, as a result of compromised hepatic artery flow, is a well-known cause of biliary strictures, sepsis, and graft failure. However, very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions (ITBL) that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise. Both the warm and cold ischemic period duration appear to influence the onset of ITBL. All of the commonly used MP techniques deliver oxygen to the graft cells, and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL. As clinical experience and published evidence grows for these modalities, the impact they have on ITBL rates is important to consider. In this review, the evidence for the three commonly used MP strategies (abdominal normothermic regional perfusion [A-NRP], hypothermic oxygenated perfusion [HOPE], and normothermic machine perfusion [NMP] for ITBL prevention has been critically reviewed. Inconsistencies with ITBL definitions used in trials, coupled with variations in techniques of MP, make interpretation challenging. Overall, the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage. The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.

Keywords: Liver transplant, Ischemic type biliary lesions, Hypothermic oxygenated machine perfusion, Normothermic machine perfusion, Abdominal normothermic regional perfusion, Donation after circulatory death

Core Tip: In recent years, the development of different machine perfusion (MP) strategies has generated interest in their use for both the assessment of grafts and optimization during the preservation period. The different mechanisms behind the diverse array of MP strategies may reduce the extent of cholangiocyte and may have the subsequent clinical effect of preventing the development of ischemic type biliary lesions (ITBL). This review summarizes the strength and limitations of clinical studies that have been undertaken, their results, and provides a summary of the available literature on MP and the prevention of ITBL.