Extended Criteria Donor Livers Research Articles

Viability assessment and transplantation of extended criteria donor liver grafts using normothermic machine perfusion

BackgroundThe scarcity of available liver grafts necessitates the use of organs from extended criteria donors, a practice associated with an increased risk of graft failure. A notable percentage of deceased donor liver allografts are rejected due to subjective criteria. Normothermic machine perfusion holds promise for introducing objective parameters into this decision-making process. The aim of this study was to compare the outcomes of standard criteria and extended criteria donor allografts after liver transplantation, following viability assessment, using normothermic machine perfusion. MethodsLiver allografts preserved by normothermic machine perfusion before liver transplantation at the University Hospital of Münster were retrospectively analyzed. Organs were stratified according to the Eurotransplant Donor Risk Index. In total, 101 liver grafts were included in this study and divided into 2 groups: (1) standard criteria donors with a Donor Risk Index <1.8 (DRI-low) and (2) extended criteria donors with a Donor Risk Index ≥1.8 (DRI-high). ResultsAn increased risk profile of donor livers, as assessed by the Eurotransplant Donor Risk Index, did not correlate with patient or graft survival. High-risk liver grafts were effectively transplanted into recipients with different risk levels after viability assessment by normothermic machine perfusion. However, the recipients’ model for end-stage liver disease scores showed a significant association with both overall patient and graft survival. ConclusionThe use of normothermic machine perfusion for viability assessment allows safe transplantation of high-risk donor livers and effectively addresses the disparity between donor liver availability and transplantation demand.

The impact of normothermic machine perfusion and acuity circles on waitlist time, mortality, and cost in liver transplantation: A multicenter experience.

Ex situ normothermic machine perfusion (NMP) helps increase the use of extended criteria donor livers. However, the impact of an NMP program on waitlist times and mortality has not been evaluated. Adult patients listed for liver transplant (LT) at 2 academic centers from January 1, 2015, to September 1, 2023, were included (n=2773) to allow all patients ≥6 months follow-up from listing. Routine NMP was implemented on October 14, 2022. Waitlist outcomes were compared from pre-NMP pre-acuity circles (n=1460), pre-NMP with acuity circles (n=842), and with NMP (n=381). Median waitlist time was 79 days (IQR: 20-232d) at baseline, 49 days (7-182) with acuity circles, and 14 days (5-56) with NMP ( p <0.001). The rate of transplant-per-100-person-years improved from 61-per-100-person-years to 99-per-100-person-years with acuity circles and 194-per-100-person-years with NMP ( p <0.001). Crude mortality without transplant decreased from 18.3% (n=268/1460) to 13.3% (n=112/843), to 6.3% (n=24/381) ( p <0.001) with NMP. The incidence of mortality without LT was 15-per-100-person-years before acuity circles, 19-per-100 with acuity circles, and 9-per-100-person-years after NMP ( p <0.001). Median Model for End-Stage Liver Disease at LT was lowest with NMP, but Model for End-Stage Liver Disease at listing was highest in this era ( p <0.0001). The median donor risk index of transplanted livers at baseline was 1.54 (1.27-1.82), 1.66 (1.42-2.16) with acuity circles, and 2.06 (1.63-2.46) with NMP ( p <0.001). Six-month post-LT survival was not different between eras ( p =0.322). The total cost of health care while waitlisted was lowest in the NMP era ($53,683 vs. $32,687 vs. $23,688, p <0.001); cost-per-day did not differ between eras ( p =0.152). The implementation of a routine NMP program was associated with reduced waitlist time and mortality without compromising short-term survival after liver transplant despite increased use of riskier grafts. Routine NMP use enables better waitlist management with reduced health care costs.

Graft repair during machine perfusion: a current overview of strategies.

With changing donor characteristics (advanced age, obesity), an increase in the use of extended criteria donor (ECD) livers in liver transplantation is seen. Machine perfusion allows graft viability assessment, but still many donor livers are considered nontransplantable. Besides being used as graft viability assessment tool, ex situ machine perfusion offers a platform for therapeutic strategies to ameliorate grafts prior to transplantation. This review describes the current landscape of graft repair during machine perfusion. Explored anti-inflammatory therapies, including inflammasome inhibitors, hemoabsorption, and cellular therapies mitigate the inflammatory response and improve hepatic function. Cholangiocyte organoids show promise in repairing the damaged biliary tree. Defatting during normothermic machine perfusion shows a reduction of steatosis and improved hepatobiliary function compared to nontreated livers. Uptake of RNA interference therapies during machine perfusion paves the way for an additional treatment modality. The possibility to repair injured donor livers during ex situ machine perfusion might increase the utilization of ECD-livers. Application of defatting agents is currently explored in clinical trials, whereas other therapeutics require further research or optimization before entering clinical research.

Application of extended criteria donor grafts in liver transplantation for acute-on-chronic liver failure: A retrospective cohort study.

There is no consensus on the usage of extended criteria donor (ECD) grafts in liver transplantation (LT) for acute-on-chronic liver failure (ACLF) patients. To summarize the experience of using ECD livers in ACLF-LT. A retrospective cohort study was conducted, enrolling patients who underwent LT at the First Affiliated Hospital of Sun Yat-Sen University from January 2015 to November 2021. The patients were divided into ECD and non-ECD groups for analysis. A total of 145 recipients were enrolled in this study, of which ECD and non-ECD recipients accounted for 53.8% and 46.2%, respectively. Donation after cardiac death (DCD) recipients accounted for the minority compared with donation after brain death (DBD) recipients (16.6% vs 83.4%). Neither overall survival nor graft survival significantly differed between ECD and non-ECD and DCD and DBD recipients. ECD grafts were associated with a significantly higher incidence of early allograft dysfunction (EAD) than non-ECD grafts (67.9% vs 41.8%, P = 0.002). Postoperative outcomes between DCD and DBD recipients were comparable (P > 0.05). ECD graft (P = 0.009), anhepatic phase (P = 0.034) and recipient gamma glutamyltransferase (P = 0.016) were independent risk factors for EAD. Recipient preoperative number of extrahepatic organ failures > 2 (P = 0.015) and intraoperative blood loss (P = 0.000) were independent predictors of poor post-LT survival. Although related to a higher risk of EAD, ECD grafts can be safely used in ACLF-LT. The main factors affecting post-LT survival in ACLF patients are their own severe preoperative disease and intraoperative blood loss.

End-ischemic hypothermic oxygenated perfusion for extended criteria donors in liver transplantation: a multicenter, randomized controlled trial—HOPExt

BackgroundGiven the scarce donor supply, an increasing number of so-called marginal or extended criteria donor (ECD) organs are used for liver transplantation. These ECD liver grafts are however known to be associated with a higher rate of early allograft dysfunction and primary non-function because of a greater vulnerability to ischemia–reperfusion injury. The end-ischemic hypothermic oxygenated machine perfusion (HOPE) technique may improve outcomes of liver transplantation with ECD grafts by decreasing reperfusion injury.MethodsHOPExt trial is a comparative open-label, multicenter, national, prospective, randomized, controlled study, in two parallel groups, using static cold storage, the gold standard procedure, as control. The trial will enroll adult patients on the transplant waiting list for liver failure or liver cirrhosis and/or liver malignancy requiring liver transplantation and receiving an ECD liver graft from a brain-dead donor. In the experimental group, ECD liver grafts will first undergo a classical static cold (4 °C) storage followed by a hypothermic oxygenated perfusion (HOPE) for a period of 1 to 4 h. The control group will consist of the classic static cold storage which is the gold standard procedure in liver transplantation. The primary objective of this trial is to study the efficacy of HOPE used before transplantation of ECD liver grafts from brain-dead donors in reducing postoperative early allograft dysfunction within the first 7 postoperative days compared to simple cold static storage.DiscussionWe present in this protocol all study procedures in regard to the achievement of the HOPExt trial, to prevent biased analysis of trial outcomes and improve the transparency of the trial results. Enrollment of patients in the HOPExt trial has started on September 10, 2019, and is ongoing.Trial registrationClinicalTrials.gov NCT03929523. Registered on April 29, 2019, before the start of inclusion.

Prolonged Normothermic Machine Perfusion: Buying More Time for Liver Graft Assessment and Repair.

Prolonged Normothermic Machine Perfusion: Buying More Time for Liver Graft Assessment and Repair.

Nanoparticle-Based Interventions for Liver Transplantation.

Liver transplantation is the only treatment for hepatic insufficiency as a result of acute and chronic liver injuries/pathologies that fail to recover. Unfortunately, there remains an enormous and growing gap between organ supply and demand. Although recipients on the liver transplantation waitlist have significantly higher mortality, livers are often not allocated because they are (i) classified as extended criteria or marginal livers and (ii) subjected to longer cold preservation time (>6 h) with a direct correlation of poor outcomes with longer cold ischemia. Downregulating the recipient's innate immune response to successfully tolerate a graft having longer cold ischemia times or ischemia-reperfusion injury through induction of immune tolerance in the graft and the host would significantly improve organ utilization and post-transplant outcomes. Broadly, technologies proposed for development aim to extend the life of the transplanted liver through post-transplant or recipient conditioning. In this review, we focus on the potential benefits of nanotechnology to provide unique pre-transplant grafting and recipient conditioning of extended criteria donor livers using immune tolerance induction and hyperthermic pre-conditioning.

Extended criteria brain-dead organ donors: Prevalence and impact on the utilisation of livers for transplantation in Brazil.

Despite its association with higher postoperative morbidity and mortality, the use of extended criteria donor (ECD) livers for transplantation has increased globally due to the high demand for the procedure. To investigate the prevalence of ECD in donation after brain death (DBD) and its impact on organ acceptance for transplantation. Retrospective analysis of DBD organ offers for liver transplantation between 2017 and 2020 in a high-volume transplant centre. The incidence of the Eurotransplant risk factors to define an ECD (ET-ECD) among DBD donors and the likelihood of organ acceptance over the years were analysed. The relationship between organ refusal for transplantation, the occurrence, and the number of ET-ECD was assessed by simple and multiple logistic regression adjustment. A total of 1619 organ donors were evaluated. Of these, 78.31% (n = 1268) had at least one ET-ECD criterion. There was an increase in the acceptance of ECD DBD organs for transplantation (1 criterion: from 23.40% to 31.60%; 2 criteria: from 13.10% to 27.70%; 3 criteria: From 6.30% to 13.60%). For each addition of one ET-ECD variable, the estimated chance of organ refusal was 64.4% higher (OR 1.644, 95%CI 1.469-1.839, P < 0.001). Except for the donor serum sodium > 165 mmol/L (P = 0.310), all ET-ECD criteria increased the estimated chance of organ refusal for transplantation. A high prevalence of ECD DBD was observed. Despite the increase in their utilisation, the presence and the number of extended donor criteria were associated with an increased likelihood of their refusal for transplantation.

Liver Resuscitation With Hypothermic Oxygenated Perfusion After Donation in Asystolic Type Iii With Regional Perfusion in Normothermia: A Case Report About First Experience in Spain

Extended criteria donor livers are increasingly being accepted for transplant in an attempt to bridge the gap between the number of patients on the waiting list and the number of available donor livers. Our objective was to describe our first case of hepatic resuscitation by means of an ex situ perfusion machine in hypothermia with oxygen insufflation of a liver graft extracted from a donor in type 3 asystole after regional perfusion in normothermia. A 53-year-old woman with disabling polycystic liver disease was included on the liver transplant waiting list. Donation was offered in type 3 asystole with regional perfusion in normothermia. Given that it was an elderly donor with a low-weight graft, hepatic resuscitation was decided by means of an ex situ perfusion machine in hypothermia with oxygen insufflation. After performing the bench work, the injector is selectively cannulated via the portal to connect it to the hypothermic perfusion machine. The average temperature of the perfusate (3 L modified Belzer) was 10°C for 120 minutes at 250 mL/min. The implant was completed without the need for transfusion of blood products, postreperfusion Sd, or vasoactive support. Peak of GOT/GPT was 803/276 at 24 hours posttransplant.

Hypothermic oxygenated perfusion in extended criteria donor liver transplantation—A randomized clinical trial

Hypothermic Oxygenated Perfusion (HOPE) of the liver can reduce the incidence of early allograft dysfunction (EAD) and failure in extended criteria donors (ECD) grafts, although data from prospective studies are very limited. In this monocentric, open-label study, from December 2018 to January 2021, 110 patients undergoing transplantation of an ECD liver graft were randomized to receive a liver after HOPE or after static cold storage (SCS) alone. The primary endpoint was the incidence of EAD. The secondary endpoints included graft and patient survival, the EASE risk score, and the rate of graft or other graft-related complications. Patients in the HOPE group had a significantly lower rate of EAD (13% vs. 35%, p=.007) and were more frequently allocated to the intermediate or higher risk group according to the EASE score (2% vs. 11%, p=.05). The survival analysis confirmed that patients in the HOPE group were associated with higher graft survival oneyear after LT (p=.03, log-rank test). In addition, patients in the SCS group had a higher re-admission and overall complication rate at sixmonths, in particular cardio-vascular adverse events (p=.04 and p=.03, respectively). HOPE of ECD grafts compared to the traditional SCS preservation method is associated with lower dysfunction rates and better graft survival.

Ex Vivo Liver Machine Perfusion: Comprehensive Review of Common Animal Models.

The most common preservation technique for liver grafts is static cold storage. Due to the organ shortage for liver transplantation (LT), extended criteria donor (ECD) allografts are increasingly used-despite the higher risk of inferior outcome after transplantation. Ex vivo liver machine perfusion (MP) has been developed to improve the outcome of transplantation, especially with ECD grafts, and is currently under evaluation in clinical trials. We performed a literature search on PubMed and ISI Web of Science to assemble an overview of rodent and porcine animal models of ex vivo liver MP for transplantation, which is essential for the present and future development of clinical liver MP. Hypothermic, subnormothermic, and normothermic MP systems have been successfully used for rat and pig LT. In comparison with hypothermic systems, normothermic perfusion often incorporates a dialysis unit. Moreover, it enables metabolic assessment of liver grafts. Allografts experiencing warm ischemic time have a superior survival rate after MP compared with cold storage alone, irrespective of the temperature used for perfusion. Furthermore, ex vivo MP improves the outcome of regular and ECD liver grafts in animal models. Small and large animal models of ex vivo liver MP are available to foster the further development of this new technology. Impact Statement Ex vivo machine perfusion is an important part of current research in the field of liver transplantation. While evidence for improve storage is constantly rising, the development of future applications such as quality assessment and therapeutic interventions necessitates robust animal models. This review is intended to provide an overview of this technology in common large and small animal models and to give an outlook on future applications. Moreover, we describe developmental steps that can be followed by others, and which can help to decrease the number of animals used for experiments based on the replace, reduce, refine concept.

Machine Perfusion for Extended Criteria Donor Livers: What Challenges Remain?

Based on the renaissance of dynamic preservation techniques, extended criteria donor (ECD) livers reclaimed a valuable eligibility in the transplantable organ pool. Being more vulnerable to ischemia, ECD livers carry an increased risk of early allograft dysfunction, primary non-function and biliary complications and, hence, unveiled the limitations of static cold storage (SCS). There is growing evidence that dynamic preservation techniques—dissimilar to SCS—mitigate reperfusion injury by reconditioning organs prior transplantation and therefore represent a useful platform to assess viability. Yet, a debate is ongoing about the advantages and disadvantages of different perfusion strategies and their best possible applications for specific categories of marginal livers, including organs from donors after circulatory death (DCD) and brain death (DBD) with extended criteria, split livers and steatotic grafts. This review critically discusses the current clinical spectrum of livers from ECD donors together with the various challenges and posttransplant outcomes in the context of standard cold storage preservation. Based on this, the potential role of machine perfusion techniques is highlighted next. Finally, future perspectives focusing on how to achieve higher utilization rates of the available donor pool are highlighted.

Normothermic liver machine perfusion as a dynamic platform for regenerative purposes: What does the future have in store for us?

Liver transplantation has become an immense success; nevertheless, far more recipients are registered on waiting lists than there are available donor livers for transplantation. High-risk, extended criteria donor livers are increasingly used to reduce the discrepancy between organ demand and supply. Especially for high-risk livers, dynamic preservation using machine perfusion can decrease post-transplantation complications and may increase donor liver utilisation by improving graft quality and enabling viability testing before transplantation. To further increase the availability of donor livers suitable for transplantation, new strategies are required that make it possible to use organs that are initially too damaged to be transplanted. With the current progress in experimental liver transplantation research, (long-term) normothermic machine perfusion may be used in the future as a dynamic platform for regenerative medicine approaches, enabling repair and regeneration of injured donor livers. Currently explored therapeutics such as defatting cocktails, RNA interference, senolytics, and stem cell therapy may assist in the repair and/or regeneration of injured livers before transplantation. This review will provide a forecast of the future utility of normothermic machine perfusion in decreasing the imbalance between donor liver demand and supply by enabling the repair and regeneration of damaged donor livers.

P11.27: Changes in Markers of Coagulation and Fibrinolysis Offer Insights Into Pathophysiological Aspects of Preservation Injury During Normothermic Liver Perfusion

Background: The perfusate used in normothermic machine perfusion (NMP) is mainly composed of red packed blood cells and colloid solution and is therefore free from thrombocytes and coagulation factors. Our aim was to monitor changes in composition of coagulation factors during NMP and to investigate their association with liver function during NMP and after transplantation. Methods: NMP has been performed on a heterogenous study group of 16 grafts that included 12 extended criteria donor livers. Factor V activity (FV), factor XIII activity (FXIII), van Willebrand factor activity (vWF), D-dimer, plasminogen-activator-inhibitor (PAI-1) and thrombocyte count in perfusate were assessed. Liver and bile duct biopsies were taken before and after perfusion and after reperfusion. Median follow-up after transplantation was 11 months (IQR: 6.4-12). Results: NMP and assessment of 16 livers resulted in 10 livers that were successfully transplanted. Main reasons for decline included inability to clear lactate, low bile quality, or signs of fibrosis in the frozen section. Two livers presented with increased D-dimer levels during perfusion (8.7 µg/mL and 12.3 µg/mL vs. mean peak D-dimer of 3.7 µg/mL SD: 3.1). One liver was transplanted, the histological analysis of the bile duct biopsies taken before implantation showed sclerosing cholangitis. Additionally, vWF activity during perfusion of this liver was increased (13 % vs. mean peak vWF activity of 6.4% SD: 2.5). The recipient had to be treated with a stent for an anastomotic stricture. The second liver with elevated D-dimer was severely steatotic and the only liver out of the study group that did not produce bile and was therefore declined for transplantation. The graft additionally presented with high levels of PAI-1 (299 IU/mL vs. mean peak PAI-1 of 186 IU/mL SD: 155) and increased FXIII activity in perfusate (158 % vs. mean peak FXIII activity 45% SD: 49). PAI-1 was also elevated in another three livers during perfusion, of which one was discarded due to increasing lactate after initial clearing and high grade of steatosis (peak PAI-1 605 IU/mL). Both other livers were successfully transplanted, one of the two recipients later developed an anastomotic stricture. Each of the three cases with increased PAI-1 levels coincided with peaks in either thrombocyte count, bilirubin or FV activity. Conclusion: Changes in perfusate composition of coagulation and fibrinolysis factors offer interesting new insights in pathophysiological aspects of preservation injury and might allow for additional graft assessment during longer courses of NMP. Prospective studies are needed to validate these initial findings.

313.6: Early Graft Disfunction After Hypothermic Oxygenated Machine Perfusion of ECD Criteria Liver Grafts: No Longer A Clinical Issue?

Introduction: Early allograft disfunction (EAD) continues to be an important issue in liver transplantation, varying from 15 to 30%. This rate is particularly high in case of extended criteria donor (ECD) grafts due to significant ischemia-reperfusion injury leading to EAD. This injury is substantially reduced by thermoregulated oxygenated machine perfusion. The aim of the paper was to assess the use of hypothermic oxygenated machine perfusion (HOPE) in ECD liver grafts in a high-volume liver transplantation center using a specific protocol. Method: Grafts with >30% macrosteatosis and with multiple ECD (at least 2 criteria) were perfused using dual HOPE (hepatic artery and portal vein perfusion), while HOPE (portal vein perfusion only) was used for the remaining ECD grafts. The main criteria to establish graft improvement were the improvement of arterial and portal perfusion flows, with lactate under 3 mmol/L throughout the procedure. Results: Between February 2016 and February 2022, 26 ECD liver grafts were harvested from DBD (donation after brain death) donors and benefitted from HOPE. Dual HOPE was used in 8 grafts (30.7%). Criteria for graft improvement were met in all grafts except 5 (19.2%), where lactate was over 3 mmol/L, with a median of 3.6 (range 3.5-6.1). The median follow-up was 5 months (range 2-44). No EAD was encountered. Conclusion: By using a combined protocol of HOPE and dual HOPE, ECD liver grafts may be safely used by avoiding early graft dysfunction.

Hypothermic oxygenated machine perfusion for extended criteria donor allografts: Preliminary experience with extended organ preservation times in the setting of organ reallocation.

In times of critical organ shortage, poor organ pool utilization and increased use of extended-criteria donor (ECD) allografts remain a major problem. Hypothermic oxygenated machine perfusion (HOPE) has emerged as a promising and feasible strategy in ECD liver transplantation (LT). However, potential safety limits regarding the duration of perfusion are yet to be explored. Besides marginal allograft quality (steatosis), prolonged cold ischemia time remains the most important factor for a high number of liver allografts being declined for transplantation. Two ECD-allografts were each allocated to two recipients, who proved to be unsuitable to receive the assigned allograft upon arrival at the transplant center. The organs were reallocated by Eurotransplant and accepted by our center for two different backup patients. During that time, HOPE was commenced and continued until the recipient hepatectomy was completed. Postoperative allograft function was assessed by serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and International Normalized Ratio. Incidence of early allograft dysfunction (EAD), postoperative complications, and length of hospital stay were analyzed. HOPE was applied for 4h 35min and 4h 20min, resulting in a total cold preservation time of 17h 29min and 15h 20min, respectively. Both recipients displayed decreasing serum transaminases and bilirubin levels postoperatively. No EAD or major postoperative complications occurred in either patient. Serum ALT and AST levels were within the normal range at discharge. Extended HOPE enables the safe extension of preservation time for up to 18h in human LT. End-ischemic HOPE may significantly improve organ pool utilization, while simultaneously facilitating operating room logistics and preventing organ injury.

Ischaemia-free liver transplantation in humans: a first-in-human trial.

SummaryBackground Ischaemia-reperfusion injury is considered an inevitable component of organ transplantation, compromising organ quality and outcomes. Although several treatments have been proposed, none has avoided graft ischaemia and its detrimental consequences.Methods Ischaemia-free liver transplantation (IFLT) comprises surgical techniques enabling continuous oxygenated blood supply to the liver of brain-dead donor during procurement, preservation, and implantation using normothermic machine perfusion technology. In this non-randomised study, 38 donor livers were transplanted using IFLT and compared to 130 conventional liver transplants (CLT).Findings Two recipients (5•3%) in the IFLT group experienced early allograft dysfunction, compared to 50•0% in patients receiving conventional transplants (absolute risk difference, 44•8%; 95% confidence interval, 33•6-55•9%). Recipients of IFLT had significantly reduced median (IQR) peak aspartate aminotransferase levels within the first week compared to CLT recipients (365, 238-697 vs 1445, 791-3244 U/L, p<0•001); likewise, median total bilirubin levels on day 7 were significantly lower (2•34, 1•39-4•09 mg/dL) in the IFLT group than in the CLT group (5•10, 1•90-11•65 mg/dL) (p<0•001). Moreover, IFLT recipients had a shorter median intensive care unit stay (1•48, 0•75-2•00 vs 1•81, 1•00-4•58 days, p=0•006). Both one-month recipient (97•4% vs 90•8%, p=0•302) and graft survival (97.4% vs 90•0%, p=0•195) were better for IFLT than CLT, albeit differences were not statistically significant. Subgroup analysis showed that the extended criteria donor livers transplanted using the IFLT technique yielded faster post-transplant recovery than did the standard criteria donor livers transplanted using the conventional approach.Interpretation IFLT provides a novel approach that may improve outcomes, and allow the successful utilisation of extended criteria livers.Funding This study was funded by National Natural Science Foundation of China, Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology, and Guangdong Provincial international Cooperation Base of Science and Technology.Panel: Research in context

The Utility of Extended Criteria Donor Livers in High Acuity Liver Transplant Recipients.

Although the use of extended criteria donor (ECD) liver allografts has gained momentum as a potential method by which to expand the donor pool, their use largely remains relegated to low acuity liver transplant (LT) recipients. Thus, we sought to examine whether such grafts also have utility in high acuity (Model for End-Stage Liver Disease [MELD] ≥ 35) recipients. Extended criteria donors were defined as donor age > 60 years, hepatitis C virus positive donor, split livers, livers with cold ischemia time > 12h, donor after cardiac death livers, or having macrosteatosis > 30%. Outcomes were compared between standard liver (SL) and ECD grafts in recipients with MELD ≥ 35. Of 225 patients, 46 (20.4%) received an ECD liver and 179 (79.6%) received a SL. Extended criteria donor graft recipients had significantly higher levels of post-LT maximal transaminases and rate of early allograft dysfunction. Nonetheless, high acuity ECD graft recipients had similar short- and long-term patient survival compared to SL recipients, with 1-,3-, and 5-year survivals of 86.9%, 82.3%, 79.3% and 86.9%, 80.5%, and 75.4%, respectively (P = .674). There were also no significant differences in graft survival or rejection-free survival between the 2 groups. The lack of inferior patient/graft survival among high acuity ECD graft recipients suggests that ECD livers present a viable method by which to expand the donor pool for this group of patients.

Continuous Normothermic Machine Perfusion for Renovation of Extended Criteria Donor Livers Without Recooling in Liver Transplantation: A Pilot Experience.

Background: Ischemia injury affects the recovery of liver allograft function. We propose a novel technique aimed at avoiding a second ischemic injury: transplanting an extended criteria donor (ECD) liver directly under normothermic machine perfusion (NMP) without recooling. We studied two cases to evaluate the efficacy and safety of this technique.Methods: The perioperative characteristics and postoperative outcomes of two recipients of ECD livers were analyzed. Both transplantations were performed with continuous normothermic machine perfusion without recooling.Result: In case 1, the cause of donor death was anoxia, and the donor liver had hypernatremia before procurement. The recipient was diagnosed with decompensated cirrhosis. His model for end-stage liver disease (MELD) score was 38. In case 2, the donor liver was from a donor after cardiac death (DCD), and the donor had elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. The recipient was diagnosed with acute hepatic failure. His MELD score was 35. Both donor livers were maintained under NMP and then transplanted without recooling. The peak ALT and AST levels after surgery were 452 and 770 U/L in case 1 and 100 and 592 U/L in case 2. Neither early allograft dysfunction (EAD) nor primary graft non-function (PNF) was present in these two cases.Conclusion: In conclusion, our results demonstrate that continuous NMP without recooling is efficacious and safe for LT with extended criteria donor livers. Further investigations of this technique will be performed to confirm these promising results.

A marginal liver graft with hyperbilirubinemia transplanted successfully by ischemia-free liver transplantation

The shortage of transplant organs remains a serious issue worldwide, and using liver grafts from extended criteria donors could expand the donor pool. Extended criteria donor liver allografts have a high chance of complications such as primary nonfunction, early allograft dysfunction, and ischemic-type biliary lesions. How to employ these extended criteria donors safely and effectively warrants further investigation. Herein, we report the successful use of a marginal donor liver with hyperbilirubinemia to save the life of an acute-on-chronic liver failure recipient using a new surgical technique: ischemia-free liver transplantation (IFLT). The graft was retrieved for transplantation due to the following reasons: (I) the recipient was in a life-threatening situation and no living donor donation candidate was available; (II) the graft was considered transplantable except for cholestasis; and (III) IFLT could reduce ischemia/reperfusion injury (IRI), resuscitate the allograft ex situ, and maintain organ viability before transplantation. The graft was transplanted successfully using the IFLT procedure. Although anatomic biliary stricture occurred after surgery, no IRI-related complications were found during the follow-up. The use of liver grafts from extended criteria donors is safe and effective under IFLT. Additional IFLT clinical studies need to be performed, particularly concerning donor management, graft selection, and ex situ resuscitation.