Mechanistic Insight and Clinical Implications of Ischemia/Reperfusion Injury Post Liver Transplantation

Abstract

Ischemia/reperfusion injury is an inevitable process during liver transplantation and can lead to a high incidence of early allograft dysfunction and graft failure. The mechanism of hepatic ischemia/reperfusion injury has been elucidated as the sequelae of microcirculation dysfunction, hypoxia, oxidative stress, and cell death. In addition, the essential role of innate and adaptive immune response in hepatic ischemia/reperfusion injury and its deleterious outcomes have been discovered. Furthermore, mechanistic studies of living donor liver transplantation have elucidated distinct features of mitochondrial and metabolic dysfunction in steatotic and small-for-size graft injury. The mechanistic findings of hepatic ischemia/reperfusion injury have laid the foundation for exploring new biomarkers; however, they are yet to be validated in large cohorts. Moreover, the molecular and cellular mechanistic analysis of hepatic ischemia/reperfusion injury has promoted the development of potential therapeutics in preclinical and clinical trials. This review summarizes the most up to date evidence for liver ischemia/reperfusion injury and puts forward the importance of the spatiotemporal microenvironment that results from microcirculation dysfunction, hypoxia, metabolic dysfunction, oxidative stress, innate immunologic response, adaptive immunity, and cell death signaling. Ischemia/reperfusion injury is an inevitable process during liver transplantation and can lead to a high incidence of early allograft dysfunction and graft failure. The mechanism of hepatic ischemia/reperfusion injury has been elucidated as the sequelae of microcirculation dysfunction, hypoxia, oxidative stress, and cell death. In addition, the essential role of innate and adaptive immune response in hepatic ischemia/reperfusion injury and its deleterious outcomes have been discovered. Furthermore, mechanistic studies of living donor liver transplantation have elucidated distinct features of mitochondrial and metabolic dysfunction in steatotic and small-for-size graft injury. The mechanistic findings of hepatic ischemia/reperfusion injury have laid the foundation for exploring new biomarkers; however, they are yet to be validated in large cohorts. Moreover, the molecular and cellular mechanistic analysis of hepatic ischemia/reperfusion injury has promoted the development of potential therapeutics in preclinical and clinical trials. This review summarizes the most up to date evidence for liver ischemia/reperfusion injury and puts forward the importance of the spatiotemporal microenvironment that results from microcirculation dysfunction, hypoxia, metabolic dysfunction, oxidative stress, innate immunologic response, adaptive immunity, and cell death signaling. SummaryHepatic ischemia/reperfusion injury post liver transplantation is characterized as spatiotemporal microenvironmental disturbance including microcirculatory dysfunction, metabolic dysregulation, oxidative stress, innate and adaptive immunologic response, and cell death signaling. The mechanistic understanding enables novel biomarkers and therapeutics development in preclinical models and clinical trials. Hepatic ischemia/reperfusion injury post liver transplantation is characterized as spatiotemporal microenvironmental disturbance including microcirculatory dysfunction, metabolic dysregulation, oxidative stress, innate and adaptive immunologic response, and cell death signaling. The mechanistic understanding enables novel biomarkers and therapeutics development in preclinical models and clinical trials. The liver is subjected to ischemia and reperfusion injury during hepatectomy, liver transplantation, and systemic shock. With improvement in surgical techniques and medical treatment, to date hepatic ischemia/reperfusion injury mostly occurs in the setting of liver transplantation. Liver transplantation provides curative treatment for end-stage liver disease and is superior to any other modality. However, allograft ischemia/reperfusion injury is an inevitable process that may lead to early allograft dysfunction (EAD), primary nonfunction, or even graft failure in the acute phase after liver transplantation.1Lee D.D. Croome K.P. Shalev J.A. et al.Early allograft dysfunction after liver transplantation: an intermediate outcome measure for targeted improvements.Ann Hepatol. 2016; 15: 53-60Crossref PubMed Scopus (76) Google Scholar,2Ito T. Naini B.V. Markovic D. et al.Ischemia-reperfusion injury and its relationship with early allograft dysfunction in liver transplant patients.Am J Transplant. 2021; 21: 614-625Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Moreover, it has been suggested that allograft ischemia/reperfusion injury also renders the new liver more susceptible to recurrent diseases, such as cancer, viral hepatitis, fibrosis, and nonalcoholic fatty liver disease.3Burra P. Becchetti C. Germani G. NAFLD and liver transplantation: disease burden, current management and future challenges.JHEP Rep. 2020; 2100192PubMed Google Scholar, 4Liu J. Lo C.M. Man K. Role of intrahepatic regional immunity in post-transplant cancer recurrence.Eng Proc. 2022; 10: 57-64Google Scholar, 5Liu X.B. Lo C.M. Cheng Q. et al.Oval cells contribute to fibrogenesis of marginal liver grafts under stepwise regulation of aldose reductase and notch signaling.Theranostics. 2017; 7: 4879-4893Crossref PubMed Scopus (6) Google Scholar Clinically, several techniques have been developed to alleviate the allograft ischemia/reperfusion injury through rapid graft procurement, shortened graft transportation, continuing machine perfusion, remote or in situ ischemic preconditioning, or even ischemia-free transplantation.6Belon A.R. Tannuri A.C.A. de Albuquerque Rangel Moreira D. et al.Impact of three methods of ischemic preconditioning on ischemia-reperfusion injury in a pig model of liver transplantation.J Invest Surg. 2022; 35: 900-909Crossref PubMed Scopus (2) Google Scholar, 7Hessheimer A.J. Polak W. Antoine C. et al.Regulations and procurement surgery in DCD liver transplantation: expert consensus guidance from the International Liver Transplantation Society.Transplantation. 2021; 105: 945-951Crossref PubMed Scopus (0) Google Scholar, 8Tang Y. Wang T. Ju W. et al.Ischemic-free liver transplantation reduces the recurrence of hepatocellular carcinoma after liver transplantation.Front Oncol. 2021; 11773535Crossref Scopus (3) Google Scholar, 9van Rijn R. Schurink I.J. de Vries Y. et al.Hypothermic machine perfusion in liver transplantation: a randomized trial.N Engl J Med. 2021; 384: 1391-1401Crossref PubMed Scopus (49) Google Scholar However, the incidence of EAD still ranges from 2%–23%.10Deschenes M. Early allograft dysfunction: causes, recognition, and management.Liver Transpl. 2013; 19: S6-8Crossref PubMed Scopus (61) Google Scholar Unfortunately, the situation is even worse when using marginal grafts from extended-criteria donors. The use of marginal grafts, such as steatotic, aged, or reduced-size graft, or organs from donors after cardiac death or HBcAb-positive individuals has greatly expanded the donor pool; however, all these conditions are independent risk factors to EAD or graft loss.11Liu J. Pang L. Ng K.T.P. et al.Compromised AMPK-PGCIα axis exacerbated steatotic graft injury mitochondrial in living donor liver Surg. 2022; PubMed Scopus (0) Google T. J. et in outcomes for marginal in liver Surg. 2020; PubMed Scopus Google Scholar the steatotic liver is the extended-criteria graft, of the high of nonalcoholic fatty liver disease the the risk of graft the of graft for donors is a graft with and is be these use primary from J. et is with fatty liver and high after 2017; PubMed Scopus (0) Google T. liver are with primary graft and high after 2017; PubMed Scopus Google Scholar The use of steatotic graft is in the setting of living donor liver transplantation, steatotic grafts are more susceptible to ischemia/reperfusion injury and are with incidence of acute phase allograft dysfunction, small-for-size and graft loss.11Liu J. Pang L. Ng K.T.P. et al.Compromised AMPK-PGCIα axis exacerbated steatotic graft injury mitochondrial in living donor liver Surg. 2022; PubMed Scopus (0) Google Scholar mitochondrial dysfunction has been suggested as the J. Pang L. Ng K.T.P. et al.Compromised AMPK-PGCIα axis exacerbated steatotic graft injury mitochondrial in living donor liver Surg. 2022; PubMed Scopus (0) Google Scholar is Hepatic ischemia/reperfusion injury can from metabolic dysfunction, oxidative stress, innate immunologic adaptive immunity, and cell death K. Liver a new understanding of the role of innate Hepatol. 2022; 19: PubMed Scopus Google Scholar understanding of the spatiotemporal of these the foundation for the development of novel biomarkers and therapeutics and can in more in the of the molecular and cellular of hepatic ischemia/reperfusion and in clinical as preclinical studies and clinical trials. Hepatic ischemia/reperfusion injury is The ischemic injury occurs as early as procurement and graft during and ischemia the and liver cells metabolic Y. et injury in liver to Hepatol. 2013; 10: PubMed Scopus Google Scholar however, the injury and is the that to the can from to as high as after the K. Lo C.M. et injury in to graft in donor liver transplantation: a of hepatic injury in with and Surg. PubMed Google Scholar The to the liver cells and the for and the and large of and K. et and on in reperfusion injury liver 21: PubMed Scopus Google Scholar, G. K. P. et that reduces after reperfusion in liver PubMed Google Scholar, R. et in hepatic ischemia/reperfusion injury. The of a with a PubMed Google Scholar, D. et cell reperfusion of the ischemic Full Text Full Text PDF PubMed Google Scholar, T. et cell injury in liver transplantation and the of Surg. 2016; PubMed Scopus Google Scholar The of and factors the dysfunction of the of the to the K. Lo C.M. et injury in to graft in donor liver transplantation: a of hepatic injury in with and Surg. PubMed Google Scholar in microcirculation the in in of the and of the of cells and K. Lo C.M. et in small-for-size liver Transpl. PubMed Scopus Google Scholar dysfunction is worse in marginal In small-for-size graft during living donor liver transplantation, the in or In such small-for-size or results in incidence of allograft dysfunction or graft loss.11Liu J. Pang L. Ng K.T.P. et al.Compromised AMPK-PGCIα axis exacerbated steatotic graft injury mitochondrial in living donor liver Surg. 2022; PubMed Scopus (0) Google T. K. et graft, small-for-size and in living donor liver transplantation.J 2020; PubMed Scopus Google Scholar The have been as high with small-for-size graft, surgical or have been to the incidence of small-for-size D. et living donor liver transplantation: can it be Surg. PubMed Scopus (6) Google T. M. et outcomes after living donor liver transplantation.J Hepatol. 2021; Full Text Full Text PDF PubMed Scopus Google Scholar injury is more deleterious through the of large of from intrahepatic and R. et of from ischemia/reperfusion PubMed Google et role of cell and cell in reperfusion injury to for transplantation Hepatol. 10: PubMed Google Scholar is mitochondrial dysfunction, and of such as and dysfunction the of the from to during ischemia/reperfusion et of reperfusion injury through mitochondrial PubMed Scopus Google Scholar In addition, of and J. Pang L. Ng K.T.P. et al.Compromised AMPK-PGCIα axis exacerbated steatotic graft injury mitochondrial in living donor liver Surg. 2022; PubMed Scopus (0) Google Scholar In steatotic grafts, mitochondrial dysfunction is more and including in mitochondrial and J. Pang L. Ng K.T.P. et al.Compromised AMPK-PGCIα axis exacerbated steatotic graft injury mitochondrial in living donor liver Surg. 2022; PubMed Scopus (0) Google Scholar of fatty can lead to of results from of in the mitochondrial Y. et of fatty liver graft injury mitochondrial 2021; 105: PubMed Scopus Google Scholar of and renders the graft more to K. M. et axis in liver ischemia-reperfusion Hepatol. 2017; Full Text Full Text PDF PubMed Scopus Google W. Y. et for ischemia/reperfusion injury of the liver reduces and Med. PubMed Scopus Google Scholar preclinical studies have that and or can the and the graft from ischemia/reperfusion R. et of from ischemia/reperfusion PubMed Google C. et from ischemia and reperfusion PubMed Scopus Google Scholar, et of liver ischemia and reperfusion Full Text Full Text PDF PubMed Scopus Google Scholar, et of graft after transplantation of fatty in the PubMed Google Scholar the oxidative after to metabolic dysfunction, mitochondrial and cell death of liver cells and K. Lo C.M. et injury in to graft in donor liver transplantation: a of hepatic injury in with and Surg. PubMed Google Scholar the of cell molecular are the and the innate immune Hepatic ischemia/reperfusion injury is an innate immune response from and immune cells The intrahepatic immune microenvironment also renders the graft more susceptible to primary disease such as fibrosis, viral hepatitis, and X.B. Lo C.M. Cheng Q. et al.Oval cells contribute to fibrogenesis of marginal liver grafts under stepwise regulation of aldose reductase and notch signaling.Theranostics. 2017; 7: 4879-4893Crossref PubMed Scopus (6) Google Y. et cells liver recurrence after transplantation.J Hepatol. 2016; Full Text Full Text PDF PubMed Scopus Google Lo C.M. et and in hepatocellular Hepatol. Full Text Full Text PDF PubMed Scopus Google Scholar The of molecular the of cells and to on cell K. et cell on and injury after liver J 2013; Full Text Full Text PDF PubMed Scopus Google Scholar, K. Y. et to liver ischemia and reperfusion injury in in J Transplant. 2017; Full Text Full Text PDF PubMed Scopus (49) Google Scholar, R. et ischemic preconditioning liver the role of Surg. PubMed Scopus (0) Google Scholar, Q. J. et liver ischemia/reperfusion PubMed Scopus Google Scholar is the that is on all the innate immune studies have the of in and ischemia/reperfusion injury in liver Y. et cells liver recurrence after transplantation.J Hepatol. 2016; Full Text Full Text PDF PubMed Scopus Google et recurrence after liver transplantation 2021; PubMed Scopus Google Scholar of the of also more from K. Y. et to liver ischemia and reperfusion injury in in J Transplant. 2017; Full Text Full Text PDF PubMed Scopus (49) Google Q. J. et liver ischemia/reperfusion PubMed Scopus Google T. et a novel of hepatic ischemia and reperfusion PubMed Scopus Google Scholar also to be in during ischemia/reperfusion injury. of the after reperfusion the to J. Y. Y. et of is in and to liver in hepatic ischemia-reperfusion J 2022; Full Text Full Text PDF PubMed Google W. J. et liver ischemia and reperfusion injury in 2020; Scopus Google Scholar with mitochondrial as the and with liver large of and the the and more innate and adaptive immune cells the can be as early as and K. Lo C.M. et injury in to graft in donor liver transplantation: a of hepatic injury in with and Surg. PubMed Google Scholar the the and the Y. et injury in liver to Hepatol. 2013; 10: PubMed Scopus Google K. Lo C.M. et injury in to graft in donor liver transplantation: a of hepatic injury in with and Surg. PubMed Google Scholar In steatotic graft and small-for-size grafts, the response is even more are during steatotic graft including aldose and Q. Ng et of in small-for-size fatty liver graft Surg. PubMed Scopus Google Lo C.M. et liver graft injury through of 2017; PubMed Scopus Google Scholar in and enables the immune to even more cells and Q. Ng et of in small-for-size fatty liver graft Surg. PubMed Scopus Google Scholar, Lo C.M. et liver graft injury through of 2017; PubMed Scopus Google Scholar, Ng Y. et of aldose reductase hepatic ischemia-reperfusion injury through Surg. PubMed Scopus Google Scholar immune such as and to a role in hepatic ischemia/reperfusion M. et of cells in hepatic and liver ischemia/reperfusion 2013; PubMed Scopus Google Scholar cells are cells that cells during adaptive studies in liver transplant models that of the on cells has the potential to hepatic ischemia/reperfusion injury and et is essential for ischemia/reperfusion injury after liver PubMed Scopus Google Scholar such as and cell T. Y. et of on cells and liver and regulation of liver ischemia-reperfusion PubMed Scopus (0) Google L. et of cell and hepatic ischemia-reperfusion 2021; Scopus Google Scholar In addition, of on cells has been to the liver from ischemia/reperfusion injury through and et hepatic cells in liver transplant ischemia-reperfusion injury in 2013; PubMed Scopus Google Scholar ischemia/reperfusion injury can the of are as P. et of cells in a model of liver ischemia/reperfusion Proc. PubMed Scopus (0) Google Scholar cells and to in the cells are also surgical after and liver transplantation and on the microenvironment for cell after L. Ng J. et cells in hepatocellular 2021; PubMed Scopus Google L. Ng K.T.P. et cells to of cells and hepatocellular carcinoma 2022; PubMed Scopus Google Scholar cells are the immune cells of the they the role in innate and adaptive immunity during hepatic ischemia/reperfusion injury. cells are a new of cells innate and adaptive immune they the as of and they to be are as and to and G. M. et a new in PubMed Scopus Google Scholar also to have on hepatic ischemia/reperfusion injury. to of ischemia/reperfusion injury in liver graft from donors with nonalcoholic fatty liver J. D. et innate cells are cells in ischemia-reperfusion injury of steatotic 2022; Scopus Google Scholar In cells to the response et expanded to alleviate hepatic ischemia-reperfusion 2022; Scholar The role of cells is more has been that cell ischemia/reperfusion through or The regulation of cells is in can of are essential to and cells L. et liver transplant ischemia/reperfusion injury PubMed Scopus (0) Google Scholar reduces the and cell and the of L. et liver transplant ischemia/reperfusion injury PubMed Scopus (0) Google Scholar In addition, for hepatic ischemia/reperfusion injury cell R. M. et on cells from hepatic ischemia-reperfusion PubMed Google Scholar the a distinct of the to a role in ischemia/reperfusion M. M. et cells from hepatic ischemia reperfusion injury in Hepatol. 2016; Full Text Full Text PDF PubMed Google Scholar the of and in ischemia/reperfusion injury has the potential to novel mechanistic and new adaptive immunity is liver graft injury can be The of adaptive immune cells renders the graft more susceptible to allograft cells and cells have been suggested to be for the ischemia/reperfusion M. M. et cells from hepatic ischemia reperfusion injury in Hepatol. 2016; Full Text Full Text PDF PubMed Google Scholar and allograft P. of cells hepatic ischemic reperfusion injury in Full Text Full Text PDF PubMed Scopus Google Scholar, R. M. et of cells and in liver J 2016; PubMed Scopus Google Scholar, J.A. et cells are of hepatic ischemia-reperfusion 2017; PubMed Scopus Google Scholar, Wang J. et of the of cells and cells is with acute hepatic a Med. 2021; 19: PubMed Scopus (3) Google Scholar with cells the Y. J. et in PubMed Google Scholar cells have been characterized with distinct such as and Y. Y. et cell and liver ischemia-reperfusion Hepatol. Full Text Full Text PDF PubMed Scopus Google Scholar, Y. et role of cell in the mechanism of liver ischemia and reperfusion injury in the PubMed Scopus Google Scholar, Y. et cells innate immune in the of liver ischemia/reperfusion PubMed Google Scholar cells to the cells or Y. et role of cell in the mechanism of liver ischemia and reperfusion injury in the PubMed Scopus Google C. et in steatotic liver ischemia and reperfusion J Full Text Full Text PDF PubMed Scopus Google T. et of from ischemia/reperfusion PubMed Scopus (0) Google Scholar cells are also during ischemia/reperfusion to in the R. J. et microenvironment the of hepatic ischemia/reperfusion injury the and of the 10: PubMed Scopus Google Q. C. Wang K. et and cells and in liver ischemia/reperfusion Transpl. 2017; PubMed Scopus Google Scholar The cells and cells is graft dysfunction or The cell is of hepatic ischemia/reperfusion cells are the and C. J. et liver transplantation ischemia-reperfusion injury J Liver PubMed Scopus Google J. et and ischemia-reperfusion injury in steatotic 2022; Scopus (0) Google Scholar in models that cells are even more cells in ischemia/reperfusion J.A. et cells are of hepatic ischemia-reperfusion 2017; PubMed Scopus Google Scholar However, the of cells and cells a high of in cell P. of cells hepatic ischemic reperfusion injury in Full Text Full Text PDF PubMed Scopus Google Scholar of the of cells in hepatic ischemia/reperfusion injury. The is also and graft injury after liver transplantation. The of the on cellular to G. et after ischemia-reperfusion in liver incidence and Full Text Full Text PDF PubMed Scopus Google C. et in liver ischemia and reperfusion Transpl. PubMed Scopus Google Scholar to be or and liver and promoted C. et hepatic ischemia/reperfusion injury and liver in Google Scholar, K. J. C. et an response for hepatic ischemia reperfusion injury and in PubMed Scopus Google Scholar, J. W. W. et role of and role of in hepatic ischemia and reperfusion J Full Text Full Text PDF PubMed Scopus (0) Google Scholar The and its role in hepatic ischemia/reperfusion injury is still under are to the is an for ischemia/reperfusion injury. and cells are through of death after to ischemia/reperfusion injury after reperfusion in the liver graft of et biomarkers may on the of cell death during early ischemia and reperfusion of liver Transplant. PubMed Scopus (0) Google M. Antoine et and cell death during hepatic ischemia/reperfusion injury in Transpl. PubMed Scopus Google Scholar In the of living donor liver transplantation, however, cell death is after and is et biomarkers may on the of cell death during early ischemia and reperfusion of liver Transplant. PubMed Scopus (0) Google Scholar In addition, or is after reduces and et liver cell during ischemia/reperfusion Transpl. PubMed Scopus Google Scholar, et of ischemia-reperfusion J Transplant. 2016; Full Text Full Text PDF PubMed Scopus (0) Google Scholar, Q. W. et of fatty to ischemia-reperfusion 2016; Scopus Google Scholar of cell death have also been as the mechanism of ischemia/reperfusion injury. is mostly in the and is with Schurink et ischemia and reperfusion of is with early allograft dysfunction after transplantation.Front 2022; Scholar The of is more when a steatotic graft is J. et to ischemia-reperfusion injury of steatotic J Full Text Full Text PDF PubMed Scopus (0) Google Scholar cell death is also in the steatotic liver of the L. et from cells to ischemia-reperfusion injury in steatotic 2022; PubMed Scopus Google Scholar, T. T. et as a risk for hepatic ischemia-reperfusion injury in liver transplantation: potential role of J Transplant. 2020; Full Text Full Text PDF PubMed Scopus Google Scholar, J. J. K. et to hepatic ischemia-reperfusion J Liver 2022; PubMed Scopus Google Scholar The response ischemia/reperfusion and the of cell death to hepatic graft failure. to be the of and K. K. et axis hepatic and in and Hepatol. 2022; Full Text Full Text PDF PubMed Scopus Google Scholar The current of ischemia/reperfusion outcome on or and and clinical Unfortunately, the of EAD to graft Markovic D. et of early allograft using the liver graft transplantation risk Surg. PubMed Scopus Google Scholar, et and of a model to early allograft failure early liver Surg. 2020; PubMed Scopus Google Scholar, L. et of a current of early allograft dysfunction in liver transplant and analysis of risk Transpl. PubMed Scopus Google Scholar, M. D. et model for the of early allograft dysfunction Transpl. 21: PubMed Scopus Google Scholar is the potential that the molecular the development of biomarkers that can be early for Hepatic and is during ischemia/reperfusion injury of after microcirculation dysfunction and are for more in the M. M. et as of outcome in 15: PubMed Scopus Google the of 2020; PubMed Scopus Google Scholar and or have been suggested to graft has been as a of EAD with the of et the of liver transplantation is an early of primary graft Surg. PubMed Scopus Google Scholar The and and However, are and all with contribute to using as is for et C. et al.Impact of in liver transplantation: graft and Hepatol. Full Text Full Text PDF PubMed Google Scholar after suggested that in EAD C. et al.Impact of in liver transplantation: graft and Hepatol. Full Text Full Text PDF PubMed Google Scholar However, is to surgical of the of a and analysis during liver transplantation. et de de J. et of and to early allograft dysfunction after liver Transplant. 2021; PubMed Scopus Google Scholar in and of the to the and that the of and with a of This has the of to and In as of early allograft failure. et K. M. et and as factors for outcomes after liver transplantation: Transplant. Scopus Google Scholar that using EAD with a and a high However, the of the is and are for is of the of hepatic ischemia/reperfusion injury. In the use of has been as the for EAD with the of early J. M. et and models of early allograft dysfunction in liver transplantation: a review of the and expert Transplant. 2022; Scopus (3) Google Scholar However, its use be validated in large of the metabolic importance of the graft dysfunction after ischemia/reperfusion injury may as metabolic The use of as biomarkers for EAD has the liver transplantation can J. Wang et of the in early allograft dysfunction and after living donor liver 2017; PubMed Scopus (3) Google Scholar With a an under the of when is under In to a the also to be an independent risk for In et M. et donor liver biomarkers with early allograft Hepatol. Full Text Full Text PDF PubMed Scopus Google Scholar a model to analysis on the from graft The model to analysis of a high of for EAD in a and have been as of EAD and graft is a and can the L. et of a current of early allograft dysfunction in liver transplant and analysis of risk Transpl. PubMed Scopus Google M. et al.Early allograft dysfunction after liver transplantation: a and of of and and Liver Transplantation PubMed Scopus Google Scholar as an independent for EAD and graft C. et is a of graft dysfunction and a of graft after liver PubMed Scopus Google Scholar With the of for the an of and suggested its use as a C. et is a of graft dysfunction and a of graft after liver PubMed Scopus Google Scholar The for EAD for However, is in and the of as a is The response as early as after its as a for EAD is of its and the of the suggested the use of high from the of graft P. R. K. et of graft high for of outcome after liver Transplant. PubMed Scopus (0) Google Scholar This of as the and to EAD with a of However, the it on the of the Furthermore, in the of machine perfusion be even analysis is as the for of the of ischemia/reperfusion however, its is the that a of the liver can be is to the of the This can be results from biomarkers with intrahepatic In the living donor liver transplant from and liver have been as the The that in with small-for-size T. et in liver is with and of graft after liver Transplant. Google Scholar In the a to be the of in the hepatic findings as early of ischemia/reperfusion injury in a ischemia/reperfusion injury after liver transplantation have been in preclinical from and et of liver ischemia and reperfusion Full Text Full Text PDF PubMed Scopus Google R. et ischemic preconditioning liver the role of Surg. PubMed Scopus (0) Google M. M. et a novel to ischemia/reperfusion after liver PubMed Scopus (0) Google Scholar, P. J. et of donors with reduces hepatic ischemia-reperfusion injury after liver transplantation in PubMed Scopus (0) Google Scholar, T. K. C. et liver in a ischemia and reperfusion 2017; PubMed Scopus (0) Google Scholar, M. P. et reduces ischemia and early graft in liver transplantation.J Hepatol. Full Text Full Text PDF PubMed Scopus (0) Google Scholar, C. et of and of its from ischemia-reperfusion injury in liver transplantation.J PubMed Google Scholar, M. R. et and after and reperfusion in for liver transplantation.J PubMed Scopus (0) Google Scholar, C. Y. Y. et of to liver transplant cells ischemia-reperfusion J Transplant. 2017; Full Text Full Text PDF PubMed Scopus (0) Google Scholar However, a clinical for the targeted In the and randomized of using and for ischemia/reperfusion injury in liver G. K. P. et that reduces after reperfusion in liver PubMed Google M. J. R. et of donor with hepatocellular ischemia-reperfusion PubMed Scopus (0) Google Scholar the liver grafts with a and that liver in and the results that primary or graft the et of the and of and in ischemia and reperfusion injury in liver transplant Transplant. 2021; PubMed Scopus (3) Google Scholar Unfortunately, the to a of for of G. K. P. et that reduces after reperfusion in liver PubMed Google and M. J. R. et of donor with hepatocellular ischemia-reperfusion PubMed Scopus (0) Google graft et as a liver to the of ischemia/reperfusion injury liver Transpl. PubMed Scopus Google graft et and and and during liver transplantation. The of and the to ischemia/reperfusion PubMed Google from after D. et liver from ischemia/reperfusion Transplant. 19: PubMed Scopus Google graft on phase and K. et of the in liver J Transplant. 7: Full Text Full Text PDF PubMed Scopus Google the graft liver cell to the et for improvement of early liver allograft a phase J Transplant. Full Text Full Text PDF PubMed Scopus Google EAD and graft et of the and of and in ischemia and reperfusion injury in liver transplant Transplant. 2021; PubMed Scopus (3) Google with graft and and graft and M. et of a on the of ischemia-reperfusion injury during liver a

Topics & Concepts