Machine perfusion and the prevention of ischemic type biliary lesions following liver transplant:What is the evidence?

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.

Current and future perspectives on acute-on-chronic liver failure: Challenges of transplantation, machine perfusion, and beyond

Acute-on-chronic liver failure(ACLF)is a syndrome that occurs in patients with chronic liver disease and is characterized by acute decompensation,organ failure and high short-term mortality.Partially due to the lack of universal diagnostic criteria,the actual ACLF prevalence remains unclear;nevertheless,it is expected to be a highly prevalent condition worldwide.Earlier transplantation is an effective protective measure for selected ACLF patients.Besides liver transplantation,diagnosing and treating precipitant events and providing supportive treatment for organ failures are currently the cornerstone of ACLF therapy.Although new clinical specific therapies have been researched,more studies are necessary to assess safety and efficacy.Therefore,future ACLF management strategies must consider measures to improve access to liver transplantation because the time window for this life-saving therapy is frequently narrow.Thus,an urgent and global discussion about allocation and prioritization for transplantation in critically ill ACLF patients is needed because there is evidence suggesting that the current model may not portray their waitlist mortality.In addition,while donor organ quality is meant to be a prognostic factor in the ACLF setting,recent evidence suggests that machine perfusion of the liver may be a safe tool to improve the donor organ pool and expedite liver transplantation in this scenario.

Application of biocompatible custom ceria nanoparticles in improving the quality of liver grafts for transplantation

Liver transplantation(LT),an ultimate and vital method for treating end-stage liver disease,is often accompanied by ischemiareperfusion injury(IRI)resulting from warm or cold ischemia of the donor liver.Organ protection techniques are used to improve the quality of liver grafts(from retrieval to implantation).Reactive oxygen species(ROS)cause oxidative stress,which is considered a crucial factor in IRI after LT.Nano antioxidants capable of scavenging ROS alleviate IRI in multiple types of organs and tissues.In this study,we synthesized ceria nanoparticles(NPs)with antioxidant properties using a pyrolysis method and covered them with phospholipid-polyethylene glycol to improve their biocompatibility in vivo.We investigated the potential organprotective effect of ceria NPs and the underlying mechanisms.Ceria NPs promoted liver function recovery after LT by attenuating IRI in liver grafts in vivo.The protective effect of ceria NPs on liver grafts was investigated by applying hypothermic oxygenated machine perfusion ex vivo.Ceria NPs attenuated hypoxia reoxygenation-or H_(2)O_(2)-induced hepatocyte injury by enhancing mitochondrial activity and ROS scavenging in vitro.These effects may be associated with the activation of the nuclear factor erythroid-derived 2-related factor 2(Nrf2)/Kelch-like ECH-associated protein 1(Keap1)/heme oxygenase 1(HO-1)signaling pathway.In conclusion,ceria NPs may serve as a promising antioxidant agent for the treatment of hepatic IRI after LT.