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Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion

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World Journal of Gastroenterology 2017年第48期23卷 8443-8451页

作者： Yuri L Boteon Richard Laing hynek mergental Gary M Reynolds Darius F Mirza Simon C Afford Ricky H Bhogal The Liver Unit University Hospitals of BirminghamMindelsohn Way The Centre for Liver Research Institute for Biomedical ResearchUniversity of Birmingham

Ischaemia-reperfusion injury(IRI) is the leading cause of injury seen in the liver following transplantation. IRI also causes injury following liver surgery and haemodynamic shock. The first cells within the liver to be injured by IRI are the liver sinusoidal endothelial cells(LSEC). Recent evidence suggests that LSEC coordinate and regulates the livers response to a variety of injuries. It is becoming increasingly apparent that the cyto-protective cellular process of autophagy is a key regulator of IRI. In particular LSEC autophagy may be an essential gatekeeper to the development of IRI. The recent availability of liver perfusion devices has allowed for the therapeutic targeting of autophagy to reduce IRI. In particular normothermic machine liver perfusion(NMP-L) allow the delivery of pharmacological agents to donor livers whilst maintaining physiological temperature and hepatic flow rates. In this review we summarise the current understanding of endothelial autophagy and how this may be manipulated during NMP-L to reduce liver IRI.

关键词： Autophagy Liver transplant Ischaemiareperfusion injury Normothermic machine liver perfusion

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

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World Journal of Gastroenterology 2023年第20期29卷 3066-3083页

作者： 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 Department of Liver Transplantation Reina Sofía University HospitalCórdoba 14004Spain The Liver Unit Queen Elizabeth Hospital BirminghamBirmingham B152THUnited Kingdom Centre for Liver and Gastrointestinal Research Institute of Immunology and ImmunotherapyUniversity of BirminghamBirmingham B152THUnited Kingdom

The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft *** to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary *** problem continues to trouble clinicians,and may have catastrophic consequences for the graft and *** injury,as a result of compromised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft ***,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 *** the warm and cold ischemic period duration appear to influence the onset of *** 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 *** clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to *** 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 *** with ITBL definitions used in trials,coupled with variations in techniques of MP,make interpretation ***,the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold *** evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.

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

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