BACKGROUND Liver transplantation(LT)is the only curative,life-saving option for children and adults with end-stage liver disease.Due to the well-known shortage and heterogeneity of grafts,split LT(SLT)is an attractive...BACKGROUND Liver transplantation(LT)is the only curative,life-saving option for children and adults with end-stage liver disease.Due to the well-known shortage and heterogeneity of grafts,split LT(SLT)is an attractive strategy to expand the donor pool and reduce waitlist times.Given increased risk of cold ischemia time with SLT,machine perfusion represents a promising option to reduce it and optimize transplant logistics and outcomes.The present communication describes various possible combinations of procurement steps to perform SLT facilitated by placing one or both grafts on a normothermic machine perfusion(NMP)closed circuit device.CASE SUMMARY A 19-month-old female with biliary atresia after failed Kasai portoenterostomy and a 42-year-old woman with unresectable intrahepatic cholangiocarcinoma were selected as recipients for a SLT from a 17-year-old male donor.The SLT generated a left lateral segment and a right trisectional graft of appropriate volume for both recipients.After a mixed in-situ and ex-situ split,in order to improve logistics,the right trisectional graft was placed on a closed circuit NMP device,following an appropriate vascular reconstruction.Both grafts were implanted with excellent short-term outcomes.CONCLUSION Use of NMP with SLT for preservation prior to implantation allows not only for graft optimization but also for significant improvement of transplant logistics.We propose various models and standardization of logistic options for combining SLT with NMP to optimize graft availability and outcomes.展开更多
BACKGROUND Marginal donation after circulatory death(DCD)liver grafts are carefully used to combat the constant shortage of donors.Clinically,the worst outcomes are mainly related to severe ischemia-reperfusion-injury...BACKGROUND Marginal donation after circulatory death(DCD)liver grafts are carefully used to combat the constant shortage of donors.Clinically,the worst outcomes are mainly related to severe ischemia-reperfusion-injury and the dangerous effect of various inflammatory cytokines(CK).The machine perfusion(MP)is a promising device to rescue these grafts.AIM To analyze the role of MP connected to a sorbent cartridge(PerSorb®)and used for very damaged DCD pig livers.METHODS Seven grafts were procured from pigs from a slaughterhouse.Grafts were made very marginal with at least 60 minutes of donor warm ischemia time and 24 hours of static-cold ischemia time:(1)3 grafts were perfused in hypothermic MP with PerSorb(Sorb);(2)2 other grafts in hypothermic MP(HMP)without the cartridge(NoSorb);and(3)The other 2 livers stored in the ice box(NoTreat).The CK were measured at HMP start(T0)and at the end(Tend).Biopsies were taken at T0 and Tend.RESULTS All 5 grafts treated with HMP had a negative lactate trend after 3 hours of treatment(8.83 at T0 vs 6.4 at Tend of Sorb;15 at T0 vs 5.45 at Tend for NoSorb,P value>0.05).At Tend,both Sorb and NoSorb groups had better hemodynamic parameters,comparable between the two groups.Enzyme-linked immunosorbent assay analysis showed a reduction of monocyte chemotactic protein-1,tumor necrosis factor-alpha and interleukin-1βfor NoSorb group at Tend and a complete downregulation to physiological levels of the same CK in Sorb livers after 3 hours of treatment.Biopsies showed a reduction of the perisinusoidal edema for the Sorb grafts compared with the NoSorb livers.CONCLUSION These data suggest a potential protective role of treatment of grafts with MP and sorbent cartridge in reducing the inflammatory response after a severe ischemic injury.展开更多
The recent editorial by Parente et al provides a balanced overview of machine perfusion(MP)in liver transplantation.While its potential to improve graft pre-servation is clear,several challenges hinder routine adoptio...The recent editorial by Parente et al provides a balanced overview of machine perfusion(MP)in liver transplantation.While its potential to improve graft pre-servation is clear,several challenges hinder routine adoption:High costs,logisti-cal complexity,lack of standardized viability criteria,limited long-term outcome data,and absence of direct comparisons between hypothermic and normothermic MP.From my experience of over 900 liver transplants without MP,and the limi-ted uptake among Korean centers,compelling evidence for its necessity remains lacking.The immunomodulatory effects of MP,particularly in ABO-incompatible or sensitized recipients,remain underexplored.Future research should integrate immune profiling,mechanistic analyses,and biomarker-guided immunosup-pression strategies into multicenter trials to clarify its role in tolerance induction and long-term graft protection.Ethical,regulatory,and policy considerations especially in resource-limited settings must also be addressed to ensure equitable access.Robust clinical and mechanistic data are essential before MP can be fully endorsed as standard care.展开更多
BACKGROUND Hyperspectral imaging(HSI)offers useful information on organ quality and has already been successfully used in kidney and liver transplantation to assess transplanted organs.Up to now,there is no case repor...BACKGROUND Hyperspectral imaging(HSI)offers useful information on organ quality and has already been successfully used in kidney and liver transplantation to assess transplanted organs.Up to now,there is no case report in the literature describing HSI for quality assessment of a machine perfused donor liver.The allocated liver from a 49-year-old female donor(161 cm,70 kg)was perfused with the OrganOx®normothermic machine perfusion system in the recommended way.Organ quality assessment was performed based on laboratory values at defined time points.In addition,the final evaluation of the liver comprised macroscopic findings and HSI of each liver segment.After discarding the organ,biopsies were taken from each segment and correlated with the results of the HSI.CASE SUMMARY The donor liver’s size(29 cm×17 cm×11 cm)and weight of 2180 g posed challenges for adequate placement within the organ container.Baseline biopsy of the liver revealed no evidence of fibrosis,steatosis or inflammation.An hour after perfusion start,measurements of the perfusate indicated a pH of 7.18,a glucose level of 404 mg/dL,and a lactate level of 1.7 mmol/L.Throughout perfusion,a significant decline in glucose levels began at the fourth hour,reaching a nadir of 20 mg/dL after eight hours.Concurrently,lactate levels steadily rose,peaking at 4.9 mmol/L after the total perfusion time of 12 hours.Macroscopic alterations(signs of congestion and reduced blood circulation)on the liver’s surface were noted,particularly pronounced in segments 2,3,and 8.HSI of these areas unveiled significant reduced oxygenation.Consequently,based on all these observations,the decision was made to discard the organ.Histological examination of the altered regions revealed congestion,necrotic changes,and dissociation of CONCLUSION This case report describes the integration of HSI in the decision making of the decline of a 49-year-old machine perfused donor liver.HSI offered useful information concerning the tissue morphology and graft viability and could therefore be a useful additional tool in assessing donor liver quality before transplantation.展开更多
BACKGROUND Normothermic liver machine perfusion(NMP)is a novel technology used to preserve and evaluate the function of liver allografts.AIM To assess NMP utilization in liver transplant(LT)practices.METHODS All adult...BACKGROUND Normothermic liver machine perfusion(NMP)is a novel technology used to preserve and evaluate the function of liver allografts.AIM To assess NMP utilization in liver transplant(LT)practices.METHODS All adult deceased-donor LT recipients between January 2021 and September 2023 in the United States were analyzed.Outcomes including discard rates,survival,preservation time and timing of surgery were compared between two groups:NMP vs non-NMP.RESULTS Between 2021 and 2023,NMP was utilized in 1493(6.3%)of all LTs in the United States.Compared to non-NMP group,NMP group had lower allograft discard rate(6.5%vs 10%,P<0.001),older recipients’age(median:47 vs 42 years,P<0.001),and higher utilization of donors from donation after circulatory death(DCD)(55%vs 11%,P<0.001).NMP group also had longer distances between recipient and donor hospitals(median:156 vs 138 miles,P<0.001),longer preser-vation time(median:12.2 vs 5.8 hours,P<0.001),and more daytime reperfusion(74%vs 55%,P<0.001).Post-transplant survival outcomes were comparable between the two groups.In a subgroup analysis of NMP,recipients in the long preservation time(≥8 hours)group had higher daytime reperfusion(78%vs 55%,P<0.001)and similar post-transplant survival when compared to the short preservation time(<8 hours)group.CONCLUSION The utilization of NMP is associated with lower discard rates and increased DCD organs for LT.NMP allows for prolonging the preservation time and increased occurrence of daytime LT,without any impact on the survival outcomes.展开更多
BACKGROUND Normothermic machine perfusion(NMP)utilizing OCS Liver is becoming increasingly common in adult liver transplantation(LT),but not in pediatric transplantation.OCS Liver has been shown to decrease post-reper...BACKGROUND Normothermic machine perfusion(NMP)utilizing OCS Liver is becoming increasingly common in adult liver transplantation(LT),but not in pediatric transplantation.OCS Liver has been shown to decrease post-reperfusion syndrome and early allograft dysfunction after transplantation.We describe the first case series of three pediatric patients who received a liver transplant using livers CASE SUMMARY Three pediatric patients,all with different etiologies of liver disease,were successfully transplanted with livers preserved with NMP.All patients are currently doing well with follow-ups of 7 to 16 months post-transplant.CONCLUSION The use of OCS Liver in pediatric LT is feasible and can be performed even in the sickest recipients with excellent outcomes.Utilization of OCS Liver can optimize donor and recipient factors to allow for optimal outcomes.展开更多
The growing demand for donor organs requires measures to expand donor pool.Those include extended criteria donors, such as elderly people, steatotic livers,donation after cardiac death, etc. Static cold storage to red...The growing demand for donor organs requires measures to expand donor pool.Those include extended criteria donors, such as elderly people, steatotic livers,donation after cardiac death, etc. Static cold storage to reduce metabolic requirements developed by Collins in late 1960 s is the mainstay and the golden standard for donated organ protection. Hypothermic machine perfusion provides dynamic organ preservation at 4°C with protracted infusion of metabolic substrates to the graft during the ex vivo period. It has been used instead of static cold storage or after it as short perfusion in transplant center. Normothermic machine perfusion(NMP) delivers oxygen, and nutrition at physiological temperature mimicking regular environment in order to support cellular function. This would minimize effects of ischemia/reperfusion injury.Potentially, NMP may help to estimate graft functionality before implantation into a recipient. Clinical studies demonstrated at least its non-inferiority or better outcomes vs static cold storage. Regular grafts donated after brain death could be safely preserved with convenient static cold storage. Except for prolonged ischemia time where hypothermic machine perfusion started in transplant center could be estimated to provide possible positive reconditioning effect. Use of hypothermic machine perfusion in regular donation instead of static cold storage or in extended criteria donors requires further investigation. Multicenter randomized clinical trial supposed to be completed in December 2021. Extended criteria donors need additional measures for graft storage and assessment until its implantation. NMP is actively evaluating promising method for this purpose.Future studies are necessary for precise estimation and confirmation to issue clinical practice recommendations.展开更多
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 earl...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.展开更多
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 o...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.展开更多
The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation.Robust evidence from numerous randomized controlled trials has been pooled by ...The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation.Robust evidence from numerous randomized controlled trials has been pooled by meta-analyses,providing the highest available evidence on the protective effect of machine perfusion(MP)over static cold storage in liver transplantation(LT).Based on a protective effect with less complications and improved graft survival,the field has seen a paradigm shift in organ preservation.This editorial focuses on the role of MP in LT and how it could become the new“gold standard”.Strong collaborative efforts are needed to explore its effects on long-term outcomes.展开更多
Background: With the increased use of extended-criteria donors, static cold storage has failed to provide optimal preservation of liver grafts, resulting in early allograft dysfunction and long-term complications Mach...Background: With the increased use of extended-criteria donors, static cold storage has failed to provide optimal preservation of liver grafts, resulting in early allograft dysfunction and long-term complications Machine perfusion(MP) is a beneficial alternative preservation strategy for donor livers, particularly fo those considered to be of suboptimal quality, and could expand the limited donor pool. Data sources: A comprehensive search in Pub Med, EMBASE, Ovid databases and Clinical Trials.gov website was conducted using the medical subject heading terms "machine perfusion", "machine preservation""liver transplantation", combined with free text terms such as "hypothermic", "normothermic" and "sub normothermic". The deadline for the search was September 30, 2017. Results: MP can be classified as hypothermic, subnormothermic, and normothermic with the tempera ture maintained at 0–12 °C, 25–34 °C and 35–38 °C, respectively. Twelve clinical trials of MP have been reported in recent years. MP effectively decreased AST/ALT level and the incidence of early allograft dys function. However, the graft and patient survival rate after MP were similar to static cold storage. The detailed clinical characteristics such as liver function, graft survival, patient survival and early allograf dysfunction were reviewed.Conclusions: Clinical trial results showed that MP improves delayed graft function, primary non-function and biliary strictures. However, MP still requires validation in large clinical trials and the key parameters during MP still require optimization.展开更多
AIM To compare the effect of University of Wisconsin(UW) solution with or without metformin, an AMP-activated protein kinase(AMPK) activator, for preserving standard and marginal liver grafts of young and aged rats ex...AIM To compare the effect of University of Wisconsin(UW) solution with or without metformin, an AMP-activated protein kinase(AMPK) activator, for preserving standard and marginal liver grafts of young and aged rats ex vivo by hypothermic machine perfusion(HMP).METHODS Eighteen young(4 mo old) and 18 aged(17 mo old)healthy male SD rats were selected and randomly divided into three groups: control group, UW solution perfusion group(UWP), and UW solution with metformin perfusion group(MUWP). Aspartate aminotransferase(AST), alanine aminotransferase(ALT), lactate dehydrogenase(LDH), interleukin-18(IL-18), and tumor necrosis factor-alpha(TNF-α) in the perfused liquid were tested. The expression levels of AMPK and endothelial nitric oxide synthase(e NOS) in liver sinusoidal endothelial cells were also examined.Additionally, microscopic evaluation of the harvested perfused liver tissue samples was done. RESULTS AST, ALT, LDH, IL-18 and TNF-α levels in the young and aged liver-perfused liquid were, respectively,significantly lower in the MUWP group than in the UWP group(P < 0.05), but no significant differences were found between the young and aged MUWP groups.Metformin increased the expression of AMPK and e NOS protein levels, and promoted the extracellular release of nitric oxide through activation of the AMPK-e NOS mediated pathway. Histological examination revealed that in the MUWP group, the extent of liver cells and tissue damage was significantly reduced compared with the UWP group.CONCLUSION The addition of metformin to the UW preservative solution for ex vivo HMP can reduce rat liver injury during cold ischemia, with significant protective effects on livers, especially of aged rats.展开更多
The 2018 Joint International Congress of ILTS,ELITA and LICAGE were held in Lisbon,Portugal on May 23–26,2018.The exciting and innovative program brought together 1144 experts in liver transplantation(LT)such as surg...The 2018 Joint International Congress of ILTS,ELITA and LICAGE were held in Lisbon,Portugal on May 23–26,2018.The exciting and innovative program brought together 1144 experts in liver transplantation(LT)such as surgeons,physicians or basic scientists from 61 countries.The presentations included 110 invited speakers,181 oral presentations,and 545 posters.This editorial highlights some of the most innovative and impactful presentations in展开更多
Although the use of extended criteria donors has increased the pool of available livers for transplant,it has also introduced the need to develop improved methods of protection against ischemia-reperfusion injury(IRI)...Although the use of extended criteria donors has increased the pool of available livers for transplant,it has also introduced the need to develop improved methods of protection against ischemia-reperfusion injury(IRI),as these"marginal"organs are particularly vulnerable to IRI during the process of procurement,preservation,surgery,and post-transplantation.In this review,we explore the current basic science research investigating therapeutics administered during ex vivo liver machine perfusion aimed at mitigating the effects of IRI in the liver transplantation process.These various categories of therapeutics are utilized during the perfusion process and include invoking the RNA interference pathway,utilizing defatting cocktails,and administering classes of agents such as vasodilators,anti-inflammatory drugs,human liver stem cell-derived extracellular vesicles,and δ-opioid agonists in order to reduce the damage of IRI.Ex vivo machine perfusion is an attractive alternative to static cold storage due to its ability to continuously perfuse the organ,effectively deliver substrates and oxygen required for cellular metabolism,therapeutically administer pharmacological or cytoprotective agents,and continuously monitor organ viability during perfusion.The use of administered therapeutics during machine liver perfusion has demonstrated promising results in basic science studies.While novel therapeutic approaches to combat IRI are being developed through basic science research,their use in clinical medicine and treatment in patients for liver transplantation has yet to be explored.展开更多
Scarcity of donor organs and the increment in patients awaiting a transplant increased the use of organs from expanded criteria donors or donation after circulatory death.Due to the suboptimal outcomes of these donor ...Scarcity of donor organs and the increment in patients awaiting a transplant increased the use of organs from expanded criteria donors or donation after circulatory death.Due to the suboptimal outcomes of these donor organs,there is an increased interest in better preservation methods,such as ex vivo machine perfusion or abdominal regional perfusion to improve outcomes.This state-ofthe-art review aims to discuss the available types of perfusion techniques,its potential benefits and the available evidence in kidney,liver and pancreas transplantation.Additionally,translational steps from animal models towards clinical studies will be described,as well as its application to clinical practice,with the focus on the Netherlands.Despite the lack of evidence from randomized controlled trials,currently available data suggest especially beneficial effects of normothermic regional perfusion on biliary complications and ischemic cholangiopathy after liver transplantation.For ex vivo machine perfusion in kidney transplantation,hypothermic machine perfusion has proven to be beneficial over static cold storage in a randomized controlled trial,while normothermic machine perfusion is currently under investigation.For ex vivo machine perfusion in liver transplantation,normothermic machine perfusion has proven to reduce discard rates and early allograft dysfunction.In response to clinical studies,hypothermic machine perfusion for deceased donor kidneys has already been implemented as standard of care in the Netherlands.展开更多
The realm of extended criteria liver transplantation created the'adjacent possible'for dynamic organ preservation.Machine perfusion of the liver greatly expanded donor organ preservation possibilities,reaching...The realm of extended criteria liver transplantation created the'adjacent possible'for dynamic organ preservation.Machine perfusion of the liver greatly expanded donor organ preservation possibilities,reaching before unattainable goals,including the mitigation of ischemia-reperfusion injury,viability assessment,and organ reconditioning prior to transplantation.However,current scientific evidence lacks uniformity between studies,perfusion protocols,and acceptance criteria.Construction of collaborative research networks for sharing knowledge should,therefore,enable the development of high-level evidence and guidelines for machine perfusion utilization,including donor acceptance criteria.Finally,this approach shall guarantee conditions for further progress to occur.展开更多
With the advances and clinical growth in liver transplantation over the last four decades the focus on expanding deceased donor organs has been in need of scientific research.In the past ten years several researchers ...With the advances and clinical growth in liver transplantation over the last four decades the focus on expanding deceased donor organs has been in need of scientific research.In the past ten years several researchers have looked at the domain of machine perfusion as it applies to deceased donor livers.The following review focuses on the clinical trials and recent advances that will likely have the earliest entrance into the clinical arena.展开更多
BACKGROUND Hypothermic machine perfusion(HMP)has demonstrated benefits in terms of early kidney transplant function compared to static cold storage.While longer preservation times have shown detrimental effects,a prev...BACKGROUND Hypothermic machine perfusion(HMP)has demonstrated benefits in terms of early kidney transplant function compared to static cold storage.While longer preservation times have shown detrimental effects,a previous paired study indicated that longer pump times(the second kidney in a pair)might lead to improved outcomes.AIM To revisit the prior paired study's somewhat unexpected results by reviewing our program's experience.METHODS A total of 61 pairs of transplant recipients who received kidneys from the same donor(2012-2021)were analyzed.Patients were divided into two groups depending on whether they were transplanted first(K1)or second(K2).Therefore,the patients in each pair had identical donor characteristics,except for time on the pump.Statistical analyses included Kaplan-Meyer analysis and paired tests,including McNemar's test,student's paired t-test,or Wilcoxon's test,as appropriate.RESULTS The two groups of recipients had similar demographics(age,body mass index,diabetes,time on dialysis,sensit-ization and retransplants).Cold ischemic times for K1 and K2 were 8.9(95%CI:7.9,9.8)and 14.7 hours(13.7,15.8)(P<0.0001),respectively.Overall,K2 had a higher rate of freedom from biopsy-proven acute rejection at 1 year(P=0.015).Delayed graft function was less common in K2,12/61(20%)than in K1,20/61(33%)(P=0.046).Finally,K2 showed a higher graft survival than K1(P=0.023).CONCLUSION Our results agree with a previous study that suggested possible advantages to longer pump times.Both studies should encourage further research into HMP's potential anti-inflammatory effect.展开更多
Background:Liver transplantation(LT)is a crucial treatment for end-stage liver disease,but the limited organ supply has led to the use of extended criteria donors(ECD).The implementation of dynamic preservation techni...Background:Liver transplantation(LT)is a crucial treatment for end-stage liver disease,but the limited organ supply has led to the use of extended criteria donors(ECD).The implementation of dynamic preservation techniques like hypothermic oxygenated machine perfusion(HOPE)is crucial in improving outcomes for ECD grafts.However,graft contamination and infection are a concern.This study aimed to evaluate the risk of infections within 10 days from LT between HOPE and static cold storage(SCS)groups and postoperative complications.Methods:A retrospective cohort study was conducted,including LT recipients transplanted at a single-center from March 2016 to June 2023.Patients were divided into HOPE and SCS groups,and propensity score matching was used to select comparable cohorts.Data on patient and donor characteristics were analyzed.Results:After propensity score matching,a cohort of 370(HOPE,n=185;SCS,n=185)patients was selected for analysis.The study found no significant differences in the rate of clinically relevant infections,microbiological positive samples,or donor-derived infections within 10 days between HOPE and SCS groups.Postoperative outcomes,as well as patient and graft survival,were also similar between the two groups.The study showed that HOPE is a feasible and safe approach,with a comparable risk of infection.Conclusions:The study results indicate that HOPE use in LT does not increase the risk of infection and is associated with similar patient and graft survival outcomes compared to SCS.These findings confirm the safety and efficacy of HOPE in LT and its potential to expand the donor pool without compromising recipient outcomes.展开更多
Background:Ischemia reperfusion injury(IRI)is a major contributing factor to organ damage in liver transplantation(LT)impacting donor organ quality and patient survival.IRI-inflicted graft injury can be reduced by usi...Background:Ischemia reperfusion injury(IRI)is a major contributing factor to organ damage in liver transplantation(LT)impacting donor organ quality and patient survival.IRI-inflicted graft injury can be reduced by using hypothermic oxygenated machine perfusion(HOPE)as a preservation strategy instead of static cold storage(SCS).The endothelial glycocalyx is highly sensitive to IRI and its degradation during graft preservation and reperfusion was previously associated with inferior postoperative outcome after LT.Here,we aimed to measure glycocalyx degradation during and after HOPE in order to evaluate its potential for viability-assessment during machine perfusion and outcome prediction in patients undergoing LT.Methods:Glycocalyx degradation was quantified via enzyme-linked immunoassay(ELISA)for its main component syndecan-1(Sdc-1)in serum of 40 patients undergoing LT after HOPE.In addition,Sdc-1 was evaluated at multiple time points during HOPE.Patients were followed up for 3.5 years to assess postoperative complications including morbidity,the development of early allograft dysfunction(EAD)and graft survival.Results:Liver grafts which later developed EAD showed significantly higher Sdc-1 concentrations after 60 min of HOPE compared to grafts exhibiting normal postoperative function(P=0.02).Receiver operating characteristic analysis revealed a strong predictive potential with an area under the curve of 0.73.A cut-off at 808 ng/mL Sdc-1 at 60 min of HOPE allowed identification of a high-risk group with an incidence of EAD of 66.7%.Sdc-1 concentrations increased during all types of HOPE but were significantly higher in HOPE versus dual HOPE(D-HOPE)after 120 min of perfusion(P=0.02).Conclusions:Sdc-1 evaluated at 60 min during HOPE allows prediction of EAD after LT.Accordingly,Sdc-1 should be considered a potential additional biomarker for viability assessment during HOPE.展开更多
文摘BACKGROUND Liver transplantation(LT)is the only curative,life-saving option for children and adults with end-stage liver disease.Due to the well-known shortage and heterogeneity of grafts,split LT(SLT)is an attractive strategy to expand the donor pool and reduce waitlist times.Given increased risk of cold ischemia time with SLT,machine perfusion represents a promising option to reduce it and optimize transplant logistics and outcomes.The present communication describes various possible combinations of procurement steps to perform SLT facilitated by placing one or both grafts on a normothermic machine perfusion(NMP)closed circuit device.CASE SUMMARY A 19-month-old female with biliary atresia after failed Kasai portoenterostomy and a 42-year-old woman with unresectable intrahepatic cholangiocarcinoma were selected as recipients for a SLT from a 17-year-old male donor.The SLT generated a left lateral segment and a right trisectional graft of appropriate volume for both recipients.After a mixed in-situ and ex-situ split,in order to improve logistics,the right trisectional graft was placed on a closed circuit NMP device,following an appropriate vascular reconstruction.Both grafts were implanted with excellent short-term outcomes.CONCLUSION Use of NMP with SLT for preservation prior to implantation allows not only for graft optimization but also for significant improvement of transplant logistics.We propose various models and standardization of logistic options for combining SLT with NMP to optimize graft availability and outcomes.
文摘BACKGROUND Marginal donation after circulatory death(DCD)liver grafts are carefully used to combat the constant shortage of donors.Clinically,the worst outcomes are mainly related to severe ischemia-reperfusion-injury and the dangerous effect of various inflammatory cytokines(CK).The machine perfusion(MP)is a promising device to rescue these grafts.AIM To analyze the role of MP connected to a sorbent cartridge(PerSorb®)and used for very damaged DCD pig livers.METHODS Seven grafts were procured from pigs from a slaughterhouse.Grafts were made very marginal with at least 60 minutes of donor warm ischemia time and 24 hours of static-cold ischemia time:(1)3 grafts were perfused in hypothermic MP with PerSorb(Sorb);(2)2 other grafts in hypothermic MP(HMP)without the cartridge(NoSorb);and(3)The other 2 livers stored in the ice box(NoTreat).The CK were measured at HMP start(T0)and at the end(Tend).Biopsies were taken at T0 and Tend.RESULTS All 5 grafts treated with HMP had a negative lactate trend after 3 hours of treatment(8.83 at T0 vs 6.4 at Tend of Sorb;15 at T0 vs 5.45 at Tend for NoSorb,P value>0.05).At Tend,both Sorb and NoSorb groups had better hemodynamic parameters,comparable between the two groups.Enzyme-linked immunosorbent assay analysis showed a reduction of monocyte chemotactic protein-1,tumor necrosis factor-alpha and interleukin-1βfor NoSorb group at Tend and a complete downregulation to physiological levels of the same CK in Sorb livers after 3 hours of treatment.Biopsies showed a reduction of the perisinusoidal edema for the Sorb grafts compared with the NoSorb livers.CONCLUSION These data suggest a potential protective role of treatment of grafts with MP and sorbent cartridge in reducing the inflammatory response after a severe ischemic injury.
文摘The recent editorial by Parente et al provides a balanced overview of machine perfusion(MP)in liver transplantation.While its potential to improve graft pre-servation is clear,several challenges hinder routine adoption:High costs,logisti-cal complexity,lack of standardized viability criteria,limited long-term outcome data,and absence of direct comparisons between hypothermic and normothermic MP.From my experience of over 900 liver transplants without MP,and the limi-ted uptake among Korean centers,compelling evidence for its necessity remains lacking.The immunomodulatory effects of MP,particularly in ABO-incompatible or sensitized recipients,remain underexplored.Future research should integrate immune profiling,mechanistic analyses,and biomarker-guided immunosup-pression strategies into multicenter trials to clarify its role in tolerance induction and long-term graft protection.Ethical,regulatory,and policy considerations especially in resource-limited settings must also be addressed to ensure equitable access.Robust clinical and mechanistic data are essential before MP can be fully endorsed as standard care.
文摘BACKGROUND Hyperspectral imaging(HSI)offers useful information on organ quality and has already been successfully used in kidney and liver transplantation to assess transplanted organs.Up to now,there is no case report in the literature describing HSI for quality assessment of a machine perfused donor liver.The allocated liver from a 49-year-old female donor(161 cm,70 kg)was perfused with the OrganOx®normothermic machine perfusion system in the recommended way.Organ quality assessment was performed based on laboratory values at defined time points.In addition,the final evaluation of the liver comprised macroscopic findings and HSI of each liver segment.After discarding the organ,biopsies were taken from each segment and correlated with the results of the HSI.CASE SUMMARY The donor liver’s size(29 cm×17 cm×11 cm)and weight of 2180 g posed challenges for adequate placement within the organ container.Baseline biopsy of the liver revealed no evidence of fibrosis,steatosis or inflammation.An hour after perfusion start,measurements of the perfusate indicated a pH of 7.18,a glucose level of 404 mg/dL,and a lactate level of 1.7 mmol/L.Throughout perfusion,a significant decline in glucose levels began at the fourth hour,reaching a nadir of 20 mg/dL after eight hours.Concurrently,lactate levels steadily rose,peaking at 4.9 mmol/L after the total perfusion time of 12 hours.Macroscopic alterations(signs of congestion and reduced blood circulation)on the liver’s surface were noted,particularly pronounced in segments 2,3,and 8.HSI of these areas unveiled significant reduced oxygenation.Consequently,based on all these observations,the decision was made to discard the organ.Histological examination of the altered regions revealed congestion,necrotic changes,and dissociation of CONCLUSION This case report describes the integration of HSI in the decision making of the decline of a 49-year-old machine perfused donor liver.HSI offered useful information concerning the tissue morphology and graft viability and could therefore be a useful additional tool in assessing donor liver quality before transplantation.
文摘BACKGROUND Normothermic liver machine perfusion(NMP)is a novel technology used to preserve and evaluate the function of liver allografts.AIM To assess NMP utilization in liver transplant(LT)practices.METHODS All adult deceased-donor LT recipients between January 2021 and September 2023 in the United States were analyzed.Outcomes including discard rates,survival,preservation time and timing of surgery were compared between two groups:NMP vs non-NMP.RESULTS Between 2021 and 2023,NMP was utilized in 1493(6.3%)of all LTs in the United States.Compared to non-NMP group,NMP group had lower allograft discard rate(6.5%vs 10%,P<0.001),older recipients’age(median:47 vs 42 years,P<0.001),and higher utilization of donors from donation after circulatory death(DCD)(55%vs 11%,P<0.001).NMP group also had longer distances between recipient and donor hospitals(median:156 vs 138 miles,P<0.001),longer preser-vation time(median:12.2 vs 5.8 hours,P<0.001),and more daytime reperfusion(74%vs 55%,P<0.001).Post-transplant survival outcomes were comparable between the two groups.In a subgroup analysis of NMP,recipients in the long preservation time(≥8 hours)group had higher daytime reperfusion(78%vs 55%,P<0.001)and similar post-transplant survival when compared to the short preservation time(<8 hours)group.CONCLUSION The utilization of NMP is associated with lower discard rates and increased DCD organs for LT.NMP allows for prolonging the preservation time and increased occurrence of daytime LT,without any impact on the survival outcomes.
文摘BACKGROUND Normothermic machine perfusion(NMP)utilizing OCS Liver is becoming increasingly common in adult liver transplantation(LT),but not in pediatric transplantation.OCS Liver has been shown to decrease post-reperfusion syndrome and early allograft dysfunction after transplantation.We describe the first case series of three pediatric patients who received a liver transplant using livers CASE SUMMARY Three pediatric patients,all with different etiologies of liver disease,were successfully transplanted with livers preserved with NMP.All patients are currently doing well with follow-ups of 7 to 16 months post-transplant.CONCLUSION The use of OCS Liver in pediatric LT is feasible and can be performed even in the sickest recipients with excellent outcomes.Utilization of OCS Liver can optimize donor and recipient factors to allow for optimal outcomes.
文摘The growing demand for donor organs requires measures to expand donor pool.Those include extended criteria donors, such as elderly people, steatotic livers,donation after cardiac death, etc. Static cold storage to reduce metabolic requirements developed by Collins in late 1960 s is the mainstay and the golden standard for donated organ protection. Hypothermic machine perfusion provides dynamic organ preservation at 4°C with protracted infusion of metabolic substrates to the graft during the ex vivo period. It has been used instead of static cold storage or after it as short perfusion in transplant center. Normothermic machine perfusion(NMP) delivers oxygen, and nutrition at physiological temperature mimicking regular environment in order to support cellular function. This would minimize effects of ischemia/reperfusion injury.Potentially, NMP may help to estimate graft functionality before implantation into a recipient. Clinical studies demonstrated at least its non-inferiority or better outcomes vs static cold storage. Regular grafts donated after brain death could be safely preserved with convenient static cold storage. Except for prolonged ischemia time where hypothermic machine perfusion started in transplant center could be estimated to provide possible positive reconditioning effect. Use of hypothermic machine perfusion in regular donation instead of static cold storage or in extended criteria donors requires further investigation. Multicenter randomized clinical trial supposed to be completed in December 2021. Extended criteria donors need additional measures for graft storage and assessment until its implantation. NMP is actively evaluating promising method for this purpose.Future studies are necessary for precise estimation and confirmation to issue clinical practice recommendations.
基金funding received in the form of the Catherine Marie Enright research scholarship from the Royal Australasian College of Surgeons to support his program of research
文摘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.
文摘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.
文摘The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation.Robust evidence from numerous randomized controlled trials has been pooled by meta-analyses,providing the highest available evidence on the protective effect of machine perfusion(MP)over static cold storage in liver transplantation(LT).Based on a protective effect with less complications and improved graft survival,the field has seen a paradigm shift in organ preservation.This editorial focuses on the role of MP in LT and how it could become the new“gold standard”.Strong collaborative efforts are needed to explore its effects on long-term outcomes.
基金supported by grants from the National Natural Science Foundation of China(81470891)China Postdoctoral Science Foundation(2017M610374)+1 种基金Science and Technology Bureau of Zhejiang Province,China(2016C33145)Innovative Research Groups of the National Natural Science Foundation of China(81421062)
文摘Background: With the increased use of extended-criteria donors, static cold storage has failed to provide optimal preservation of liver grafts, resulting in early allograft dysfunction and long-term complications Machine perfusion(MP) is a beneficial alternative preservation strategy for donor livers, particularly fo those considered to be of suboptimal quality, and could expand the limited donor pool. Data sources: A comprehensive search in Pub Med, EMBASE, Ovid databases and Clinical Trials.gov website was conducted using the medical subject heading terms "machine perfusion", "machine preservation""liver transplantation", combined with free text terms such as "hypothermic", "normothermic" and "sub normothermic". The deadline for the search was September 30, 2017. Results: MP can be classified as hypothermic, subnormothermic, and normothermic with the tempera ture maintained at 0–12 °C, 25–34 °C and 35–38 °C, respectively. Twelve clinical trials of MP have been reported in recent years. MP effectively decreased AST/ALT level and the incidence of early allograft dys function. However, the graft and patient survival rate after MP were similar to static cold storage. The detailed clinical characteristics such as liver function, graft survival, patient survival and early allograf dysfunction were reviewed.Conclusions: Clinical trial results showed that MP improves delayed graft function, primary non-function and biliary strictures. However, MP still requires validation in large clinical trials and the key parameters during MP still require optimization.
基金Supported by the National Natural Science Foundation,No.81470896the Project of Development and Innovation Team of Ministry of Education,No.IRT_16R57
文摘AIM To compare the effect of University of Wisconsin(UW) solution with or without metformin, an AMP-activated protein kinase(AMPK) activator, for preserving standard and marginal liver grafts of young and aged rats ex vivo by hypothermic machine perfusion(HMP).METHODS Eighteen young(4 mo old) and 18 aged(17 mo old)healthy male SD rats were selected and randomly divided into three groups: control group, UW solution perfusion group(UWP), and UW solution with metformin perfusion group(MUWP). Aspartate aminotransferase(AST), alanine aminotransferase(ALT), lactate dehydrogenase(LDH), interleukin-18(IL-18), and tumor necrosis factor-alpha(TNF-α) in the perfused liquid were tested. The expression levels of AMPK and endothelial nitric oxide synthase(e NOS) in liver sinusoidal endothelial cells were also examined.Additionally, microscopic evaluation of the harvested perfused liver tissue samples was done. RESULTS AST, ALT, LDH, IL-18 and TNF-α levels in the young and aged liver-perfused liquid were, respectively,significantly lower in the MUWP group than in the UWP group(P < 0.05), but no significant differences were found between the young and aged MUWP groups.Metformin increased the expression of AMPK and e NOS protein levels, and promoted the extracellular release of nitric oxide through activation of the AMPK-e NOS mediated pathway. Histological examination revealed that in the MUWP group, the extent of liver cells and tissue damage was significantly reduced compared with the UWP group.CONCLUSION The addition of metformin to the UW preservative solution for ex vivo HMP can reduce rat liver injury during cold ischemia, with significant protective effects on livers, especially of aged rats.
基金supported by grants from China Postdoctoral Science Foundation(2017M610374)National Natural Science Foundation of China(81470891)+2 种基金Science and Technology Bureau of Zhejiang Province,China(2016C33145)Innovative Research Groups of the National Natural Science Foundation of China(81421062)the Fundamental Research Funds for the Central Universities(2018FZA7003)
文摘The 2018 Joint International Congress of ILTS,ELITA and LICAGE were held in Lisbon,Portugal on May 23–26,2018.The exciting and innovative program brought together 1144 experts in liver transplantation(LT)such as surgeons,physicians or basic scientists from 61 countries.The presentations included 110 invited speakers,181 oral presentations,and 545 posters.This editorial highlights some of the most innovative and impactful presentations in
文摘Although the use of extended criteria donors has increased the pool of available livers for transplant,it has also introduced the need to develop improved methods of protection against ischemia-reperfusion injury(IRI),as these"marginal"organs are particularly vulnerable to IRI during the process of procurement,preservation,surgery,and post-transplantation.In this review,we explore the current basic science research investigating therapeutics administered during ex vivo liver machine perfusion aimed at mitigating the effects of IRI in the liver transplantation process.These various categories of therapeutics are utilized during the perfusion process and include invoking the RNA interference pathway,utilizing defatting cocktails,and administering classes of agents such as vasodilators,anti-inflammatory drugs,human liver stem cell-derived extracellular vesicles,and δ-opioid agonists in order to reduce the damage of IRI.Ex vivo machine perfusion is an attractive alternative to static cold storage due to its ability to continuously perfuse the organ,effectively deliver substrates and oxygen required for cellular metabolism,therapeutically administer pharmacological or cytoprotective agents,and continuously monitor organ viability during perfusion.The use of administered therapeutics during machine liver perfusion has demonstrated promising results in basic science studies.While novel therapeutic approaches to combat IRI are being developed through basic science research,their use in clinical medicine and treatment in patients for liver transplantation has yet to be explored.
文摘Scarcity of donor organs and the increment in patients awaiting a transplant increased the use of organs from expanded criteria donors or donation after circulatory death.Due to the suboptimal outcomes of these donor organs,there is an increased interest in better preservation methods,such as ex vivo machine perfusion or abdominal regional perfusion to improve outcomes.This state-ofthe-art review aims to discuss the available types of perfusion techniques,its potential benefits and the available evidence in kidney,liver and pancreas transplantation.Additionally,translational steps from animal models towards clinical studies will be described,as well as its application to clinical practice,with the focus on the Netherlands.Despite the lack of evidence from randomized controlled trials,currently available data suggest especially beneficial effects of normothermic regional perfusion on biliary complications and ischemic cholangiopathy after liver transplantation.For ex vivo machine perfusion in kidney transplantation,hypothermic machine perfusion has proven to be beneficial over static cold storage in a randomized controlled trial,while normothermic machine perfusion is currently under investigation.For ex vivo machine perfusion in liver transplantation,normothermic machine perfusion has proven to reduce discard rates and early allograft dysfunction.In response to clinical studies,hypothermic machine perfusion for deceased donor kidneys has already been implemented as standard of care in the Netherlands.
文摘The realm of extended criteria liver transplantation created the'adjacent possible'for dynamic organ preservation.Machine perfusion of the liver greatly expanded donor organ preservation possibilities,reaching before unattainable goals,including the mitigation of ischemia-reperfusion injury,viability assessment,and organ reconditioning prior to transplantation.However,current scientific evidence lacks uniformity between studies,perfusion protocols,and acceptance criteria.Construction of collaborative research networks for sharing knowledge should,therefore,enable the development of high-level evidence and guidelines for machine perfusion utilization,including donor acceptance criteria.Finally,this approach shall guarantee conditions for further progress to occur.
文摘With the advances and clinical growth in liver transplantation over the last four decades the focus on expanding deceased donor organs has been in need of scientific research.In the past ten years several researchers have looked at the domain of machine perfusion as it applies to deceased donor livers.The following review focuses on the clinical trials and recent advances that will likely have the earliest entrance into the clinical arena.
基金This study was reviewed and approved by our local Research Ethics Board(Bio-REB#1894).
文摘BACKGROUND Hypothermic machine perfusion(HMP)has demonstrated benefits in terms of early kidney transplant function compared to static cold storage.While longer preservation times have shown detrimental effects,a previous paired study indicated that longer pump times(the second kidney in a pair)might lead to improved outcomes.AIM To revisit the prior paired study's somewhat unexpected results by reviewing our program's experience.METHODS A total of 61 pairs of transplant recipients who received kidneys from the same donor(2012-2021)were analyzed.Patients were divided into two groups depending on whether they were transplanted first(K1)or second(K2).Therefore,the patients in each pair had identical donor characteristics,except for time on the pump.Statistical analyses included Kaplan-Meyer analysis and paired tests,including McNemar's test,student's paired t-test,or Wilcoxon's test,as appropriate.RESULTS The two groups of recipients had similar demographics(age,body mass index,diabetes,time on dialysis,sensit-ization and retransplants).Cold ischemic times for K1 and K2 were 8.9(95%CI:7.9,9.8)and 14.7 hours(13.7,15.8)(P<0.0001),respectively.Overall,K2 had a higher rate of freedom from biopsy-proven acute rejection at 1 year(P=0.015).Delayed graft function was less common in K2,12/61(20%)than in K1,20/61(33%)(P=0.046).Finally,K2 showed a higher graft survival than K1(P=0.023).CONCLUSION Our results agree with a previous study that suggested possible advantages to longer pump times.Both studies should encourage further research into HMP's potential anti-inflammatory effect.
文摘Background:Liver transplantation(LT)is a crucial treatment for end-stage liver disease,but the limited organ supply has led to the use of extended criteria donors(ECD).The implementation of dynamic preservation techniques like hypothermic oxygenated machine perfusion(HOPE)is crucial in improving outcomes for ECD grafts.However,graft contamination and infection are a concern.This study aimed to evaluate the risk of infections within 10 days from LT between HOPE and static cold storage(SCS)groups and postoperative complications.Methods:A retrospective cohort study was conducted,including LT recipients transplanted at a single-center from March 2016 to June 2023.Patients were divided into HOPE and SCS groups,and propensity score matching was used to select comparable cohorts.Data on patient and donor characteristics were analyzed.Results:After propensity score matching,a cohort of 370(HOPE,n=185;SCS,n=185)patients was selected for analysis.The study found no significant differences in the rate of clinically relevant infections,microbiological positive samples,or donor-derived infections within 10 days between HOPE and SCS groups.Postoperative outcomes,as well as patient and graft survival,were also similar between the two groups.The study showed that HOPE is a feasible and safe approach,with a comparable risk of infection.Conclusions:The study results indicate that HOPE use in LT does not increase the risk of infection and is associated with similar patient and graft survival outcomes compared to SCS.These findings confirm the safety and efficacy of HOPE in LT and its potential to expand the donor pool without compromising recipient outcomes.
文摘Background:Ischemia reperfusion injury(IRI)is a major contributing factor to organ damage in liver transplantation(LT)impacting donor organ quality and patient survival.IRI-inflicted graft injury can be reduced by using hypothermic oxygenated machine perfusion(HOPE)as a preservation strategy instead of static cold storage(SCS).The endothelial glycocalyx is highly sensitive to IRI and its degradation during graft preservation and reperfusion was previously associated with inferior postoperative outcome after LT.Here,we aimed to measure glycocalyx degradation during and after HOPE in order to evaluate its potential for viability-assessment during machine perfusion and outcome prediction in patients undergoing LT.Methods:Glycocalyx degradation was quantified via enzyme-linked immunoassay(ELISA)for its main component syndecan-1(Sdc-1)in serum of 40 patients undergoing LT after HOPE.In addition,Sdc-1 was evaluated at multiple time points during HOPE.Patients were followed up for 3.5 years to assess postoperative complications including morbidity,the development of early allograft dysfunction(EAD)and graft survival.Results:Liver grafts which later developed EAD showed significantly higher Sdc-1 concentrations after 60 min of HOPE compared to grafts exhibiting normal postoperative function(P=0.02).Receiver operating characteristic analysis revealed a strong predictive potential with an area under the curve of 0.73.A cut-off at 808 ng/mL Sdc-1 at 60 min of HOPE allowed identification of a high-risk group with an incidence of EAD of 66.7%.Sdc-1 concentrations increased during all types of HOPE but were significantly higher in HOPE versus dual HOPE(D-HOPE)after 120 min of perfusion(P=0.02).Conclusions:Sdc-1 evaluated at 60 min during HOPE allows prediction of EAD after LT.Accordingly,Sdc-1 should be considered a potential additional biomarker for viability assessment during HOPE.
