Machine Perfusion Research Articles

Bridging Therapies-Ex Vivo Liver Xenoperfusion and the Role of Machine Perfusion: An Update.

Advancements in xenotransplantation intersecting with modern machine perfusion technology offer promising solutions to patients with liver failure providing a valuable bridge to transplantation and extending graft viability beyond current limitations. Patients facing acute or acute chronic liver failure, post-hepatectomy liver failure, or fulminant hepatic failure often require urgent liver transplants which are severely limited by organ shortage, emphasizing the importance of effective bridging approaches. Machine perfusion is now increasingly used to test and use genetically engineered porcine livers in translational studies, addressing the limitations and costs of non-human primate models. Current reports about artificial and bioartificial liver support combined with xenografts showcase the potential in ex vivo xenogeneic perfusion. Breakthroughs, such as the perfusion of genetically modified porcine liver with FDA-approved machine perfusion systems connected to human blood circulation, underscore the interest and potential feasibility of a "liver dialysis" bridge to allotransplantation or recovery. This review provides an overview of the past and current research in the field of ex vivo pig liver xenoperfusion.

The 2024 American Association for Thoracic Surgery expert consensus document: Current standards in donor lung procurement and preservation.

Donor lung procurement and preservation is critical for lung transplantationsuccess. Unfortunately, the large variability in techniques impacts organ utilization rates and transplantation outcomes. Compounding this variation, recent developments in cold static preservation and new technological advances with machine perfusion have increased the complexity of the procedure. The objective of the American Association for Thoracic Surgery (AATS) Clinical Practice Standards Committee (CPSC) expert panel was to make evidence-based recommendations for best practices in donor lung procurement and preservationbased on review of the existing literature. The AATS CPSC assembled an expert panel of 16 lung transplantation surgeons from 14 centers who developed a consensus document of recommendations. The panel was divided into 7 subgroups covering (1) intraoperative donor assessment, (2) surgical techniques, (3) ex situ static lung preservation methods, (4) hypothermic preservation, (5) normothermic exvivo lung perfusion (EVLP), (6) donation after circulatory death (DCD) and normothermic regional perfusion, and (7) donor management centers, organ assessment centers, and third-party procurementteams. Following a focused literature review, each subgroup formulated recommendation statements for each subtopic, which were reviewed and further refined using a Delphi process until a 75% consensus was achieved on each final statement by the voting group. The expert panel achieved consensus on 34 recommendations for current best practices in donor lung procurement and preservation both in brain-dead as well as DCD donation. The use of new methods of cold preservation, the role of EVLP, and DCD with and without concomitant heart donation are described in detail. Consistent and best practices in donor lung procurement and preservationare critical to improve both lung transplantation numbers as well as recipient outcomes. The recommendations described here provide guidance forprofessionals involved in the care of patients with end-stage lung disease considered for transplantation.

Viability Assessment During Normothermic Machine Liver Perfusion: A Literature Review.

The discrepancy between donor organ availability and demand leads to a significant waiting-list dropout rate and mortality. Although quantitative tools such as the Donor Risk Index (DRI) help assess organ suitability, many potentially viable organs are still discarded due to the lack of universally accepted markers to predict post-transplant outcomes. Normothermic machine perfusion (NMP) offers a platform to assess viability before transplantation. Thus, livers considered unsuitable for transplantation based on the DRI can be evaluated and potentially transplanted. During NMP, various viability criteria have been proposed. These criteria are neither homogeneous nor consensual. In this review, we aimed to describe the viability criteria during NMP and evaluate their ability to predict hepatic graft function following transplantation. We conducted a PubMed search using the terms 'liver transplantation', 'normothermic machine perfusion' and 'assessment', including only English publications up to February 2024. Viability assessment during NMP includes multiple hepatocellular and cholangiocellular criteria. Lactate clearance and bile production are commonly used indicators, but their ability to predict post-transplant outcomes varies significantly. The predictive value of cholangiocellular criteria such as bile pH, bicarbonate and glucose levels remains under investigation. Novel markers, such as microRNAs and proteomic profiles, offer the potential to enhance graft evaluation accuracy and provide insights into the molecular mechanisms underlying liver viability. Combining perfusion parameters with biomarkers may improve the prediction of long-term graft survival. Future research should focus on standardising viability assessment protocols and exploring real-time biomarker evaluations, which could enhance transplantation outcomes and expand the donor pool.

Physiological arterial pressure improves renal performance during normothermic machine perfusion in a porcine kidney DCD model.

Normothermic machine perfusion (NMP) provides a platform for kidney quality assessment. Donation after circulatory death (DCD) donor kidneys are associated with great ischemic injury and high intrarenal resistance (IRR). This experimental study aims to investigate the impact of different perfusion pressures on marginal kidney function and injury during NMP. Twenty-seven slaughterhouse porcine kidneys were retrieved and subjected to 60min of warm ischemia time to mimic DCD condition. These kidneys were randomized into 75mmHg (subphysiological, n=9), 95mmHg (physiological, n=9), and 115mmHg NMP (high physiological, n=9). Renal function and injury were assessed during NMP. Three groups showed comparable IRR, with the 115mmHg group exhibiting the highest blood flow. The 95mmHg group [0.48 (0.36-1.15) ml/min/100g] and 115mmHg group [0.93 (0.45-1.41) ml/min/100g] showed significantly higher creatinine clearance compared to the 75mmHg group [0.16 (0.08-0.37) ml/min/100g] during the first hour of NMP (p=0.049, p=0.009, respectively). The 115mmHg group exhibited significantly higher oxygen consumption compared to the 75mmHg group at 30min of NMP [1.37 (1.05-1.92) versus 0.72 (0.61-0.82) mlO2/min/100g, p=0.009]. Perfusate neutrophil gelatinase-associated lipocalin (NGAL) levels were consistently lowest in the 95mmHg group and highest in the 75mmHg group. Aspartate aminotransferase (AST) levels of the 115mmHg group were significantly higher than the 75mmHg group. For kidneys with high IRR, both 95mmHg and 115mmHg perfusion pressures enable an early improvement in renal hemodynamics and function compared to 75mmHg during NMP, while a high physiological perfusion can cause additional injury.

Does Normothermic Machine Perfusion Still Provide an Advantage for Deceased Donor Kidney Transplantation? A Systematic Review and Preliminary Meta-Analysis.

Patients with end-stage renal disease often face prolonged waiting times for kidney transplants. Historically, the use of marginal kidneys was limited due to suboptimal preservation methods. Normothermic machine perfusion (NMP) preserves physiological activity during the preservation process, potentially improving graft function and viability, expanding the use of marginal kidneys. While preliminary results are promising, NMP has not yet undergone sufficient clinical trials to determine whether it offers advantages over more widely used techniques. The aim of this systematic review is to assess several outcomes between kidneys that underwent NMP compared to traditional preservation methods after kidney transplant. A systematic review was conducted following PRISMA guidelines. Randomized controlled trials, case series, and studies comparing NMP with hypothermic machine perfusion (HMP) or static cold storage (SCS) were included. The primary outcome assessed was delayed graft function (DGF). Secondary outcomes included primary non-function (PNF), acute rejection, and 1-year graft survival. Eight NMP studies met the inclusion criteria. Meta-analysis showed significant differences in DGF between NMP and control (HMP or SCS) groups (OR: 0.47 [0.22, 0.99], p < 0.05). There were no significant differences between NMP and controls for PNF, acute rejection, or 1-year graft survival. These findings suggest that NMP yields similar adverse outcome rates compared to traditional methods. Notably, NMP could be associated with reduced rates of DGF. While NMP is a promising technique for renal allograft preservation, further randomized controlled trials are necessary to definitively establish its benefits over conventional preservation methods.

Improved Outcomes and Resource Use With Normothermic Machine Perfusion in Liver Transplantation.

Normothermic machine perfusion (NMP) has been shown to reduce peritransplant complications. Despite increasing NMP use in liver transplant (LT), there is a scarcity of real-world clinical experience data. To compare LT outcomes between donation after brain death (DBD) and donation after circulatory death (DCD) allografts preserved with NMP or static cold storage (SCS). This single-center, retrospective observational cohort study included all consecutive adult LTs performed between January 2019 and December 2023 at the Mayo Clinic in Arizona. Data analysis was performed between February 2024 and June 2024. Outcomes of DBD-SCS, DBD-NMP, DCD-SCS, and DCD-NMP transplants were compared. DBD and DCD livers preserved on NMP or SCS. The primary outcomes were early allograft dysfunction (EAD), intraoperative transfusion, and post-LT hospital resource use, including length of stay (LOS) and readmissions. Secondary outcomes included acute kidney injury (AKI) and 1-year graft and patient survival. A total of 1086 LTs were included in the following 4 groups: DBD-SCS (n = 480), DBD-NMP (n = 63), DCD-SCS (n = 264), and DCD-NMP (n = 279). Among LT recipients, median (IQR) age was 60.0 years (52.0-66.0); 399 LT recipients (36.7%) were female. DCD-NMP had the lowest EAD rate (17.5%), followed by DCD-SCS (50.0%), DBD-NMP (36.8%), and DBD-SCS (27.3%) (P < .001). DCD-NMP had the lowest intraoperative transfusion requirement compared to all other groups. Hospital and intensive care unit (ICU) LOS were shortest in DCD-NMP (median [IQR] hospital LOS, 5.0 days [4.0-7.0]; P = .01; median [IQR] ICU LOS, 1.5 days [1.2-3.1]; P = .01). One-year cumulative readmission probability was 86% lower for DCD-NMP vs DCD-SCS (95% CI, 0.09-0.22; P < .001) and 53% lower for DBD-NMP vs DBD-SCS (95% CI, 0.26-0.87; P < .001). AKI events were lower in DCD-NMP (31.1%) vs DCD-SCS (47.4%) (P = .001). Compared to SCS, the NMP group had a 78% overall reduction in graft failure (hazard ratio [HR], 0.22; 95% CI, 0.10-0.49; P < .001). For those receiving DCD allografts, the risk reduction was even more pronounced, with an 87% decrease in graft failure (HR, 0.13; 95% CI, 0.05-0.33; P < .001). NMP was significantly protective from patient mortality vs SCS (HR, 0.31; 95% CI, 0.12-0.80; P = .02). In this observational high-volume cohort study, NMP significantly improved LT clinical outcomes and reduced hospital resource use, especially in DCD allografts. NMP may enhance access to LT by addressing the challenges historically linked with DCD liver use.

Machine perfusion strategies in Liver Transplantation: A systematic review, pairwise, and network meta-analysis of randomized controlled trials.

Machine perfusion (MP), including hypothermic oxygenated machine perfusion (HOPE), dual HOPE, normothermic machine perfusion (NMP), NMP ischemia-free liver transplantation (NMP-ILT), and controlled oxygenated rewarming (COR), is increasingly being investigated to improve liver graft quality from extended criteria donors and donors after circulatory death and expand the donor pool. This network meta-analysis investigates the comparative efficacy and safety of various liver MP strategies versus traditional static cold storage (SCS). We searched PubMed, Scopus, Web of Science, and Cochrane Controlled Register of Trials for randomized controlled trials (RCTs) comparing liver transplantation (LT) outcomes between SCS and MP techniques. The primary outcome was the incidence of early allograft dysfunction (EAD). Secondary endpoints included 1-year graft survival, the incidence of graft failure/loss, post-reperfusion syndrome, biliary complications, the need for renal replacement therapy (RRT), graft-related patient mortality, and the length of intensive care unit (ICU) and hospital stay. R-software was used to conduct a network meta-analysis using a frequentist framework. CRD42024549254. We included 12 RCTs involving 1,628 patients undergoing LT (801 in the liver MP groups and 832 in the SCS group). Compared to SCS, HOPE/dHOPE, but not other MP strategies, was associated with a significantly lower risk of EAD (RR: 0.53, 95% CI [0.37, 0.74], p=0.0002), improved 1-year graft survival rate (RR: 1.07, 95% CI [1.01, 1.14], p=0.02), decreased graft failure/loss (RR: 0.38, 95% CI [0.16, 0.90], p=0.03), and reduced the risk of biliary complications (RR: 0.52, 95% CI [0.43, 0.75], p < 0.0001). Compared to SCS, NMP (RR: 0.49, 95% CI [0.24, 0.96] and NMP-ILT (RR: 0.15, 95% CI [0.04, 0.57], both significantly reduced the risk of post-perfusion syndrome. There is no difference between SCS and MP groups in the risk of RRT, graft-related patient mortality, and ICU and hospital stay length. Our meta-analysis showed that HOPE/dual-HOPE is a promising alternative to SCS for donor liver preservation. These new techniques can help expand the donor pool with similar or even better post-LT outcomes.

Designer Organs: Ethical Genetic Modifications in the Era of Machine Perfusion.

Gene therapy is a rapidly developing field, finally yielding clinical benefits. Genetic engineering of organs for transplantation may soon be an option, thanks to convergence with another breakthrough technology, ex vivo machine perfusion (EVMP). EVMP allows access to the functioning organ for genetic manipulation prior to transplant. EVMP has the potential to enhance genetic engineering efficiency, improve graft survival, and reduce posttransplant complications. This will enable genetic modifications with a vast variety of applications, while raising questions on the ethics and regulation of this emerging technology. This review provides an in-depth discussion of current methodologies for delivering genetic vectors to transplantable organs, particularly focusing on the enabling role of EVMP. Organ-by-organ analysis and key characteristics of various vector and treatment options are assessed. We offer a road map for research and clinical translation, arguing that achieving scientific benchmarks while creating anticipatory governance is necessary to secure societal benefit from this technology.

Hypothermic machine perfusion in uterus transplantation in a porcine model: A proof of concept and the first results in graft preservation.

Graft optimization is a necessity in order to develop uterus transplantation from brain-dead donors, as a complement to living donors, as these grafts are rare and the last organs retrieved in multiple organ donation. The aim of this study was to assess the feasibility and interest of hypothermic machine perfusion (HMP) in uterus transplantation using a porcine model; secondary outcomes were the evaluation of the graft's tolerance to a prolonged cold ischaemia time and to find new biomarkers of uterus viability. Fifteen uterus allotransplantations were performed in a porcine model, after 18 h of cold ischaemia, divided in three groups: Static cold storage in a HTK solution, HMP (with the VitaSmart (™) machine Bridge to Life Ltd.) with a UW-MP solution, and static cold storage in a UW solution. The main outcome was macroscopic: uterine arteries pulsatility, recoloration, and bleeding at the cut. Secondary outcomes were histological analyses (Zitkute and inflammation scores), caspase3 immunohistochemistry and plasmatic dosage of biomarkers. 14/15 allotransplantations were performed according to the protocol and met the criteria of macroscopic vitality. Grafts treated with HMP (MP did not show significantly more tissue) damage than the recipient's uterus, contrary to grafts in static cold storage, independently of the solution used. This difference disappeared one and 3 h after uterus transplantation. Plasma dosages before and after uterus transplantation did not allow to identify a new biomarker of uterus viability. HMP is feasible in a porcine model, without inflicting damage on the grafts during cold ischaemia time. Grafts exposed to HMP seemed to better endure reperfusion phenomena, but this advantage did not last over time.

Continuous Blood Gas Control Based on Active Disturbance Rejection Control During ExVivo Porcine Liver Perfusion.

Membrane oxygenators facilitate extracorporeal gas exchange, necessitating the monitoring of blood gas. Recent advances in normothermic machine perfusion (NMP) for exvivo liver offer solutions to the shortage of donor liver. However, maintaining physiological blood gas levels during prolonged NMP is complex and costly. We introduce a noninvasive and economical approach for regulating the blood gas during NMP of exvivo porcine livers. By monitoring gas fractions at the outlet of oxygenator, real-time adjustments of blood gas can be made without the online blood gas analyzer. The method involves constructing multivariate linear regression (MLR) models, aligning target setpoints of gas, and employing active disturbance rejection control (ADRC) to achieve closed-loop regulation. Ex vivo porcine liver perfusion experiments demonstrated the effectiveness of the method, maintaining blood gas within physiological levels over 24 h (oxygen partial pressure: 150.36 ± 3.33 mmHg, carbon dioxide partial pressure: 41.34 ± 0.91 mmHg). ADRC-based continuous regulation of gas fraction at the outlet of oxygenator is a feasible and effective approach for managing blood gas during exvivo porcine liver perfusion.

Short (2-Hour) Non-Oxygenated End-Ischemic Hypothermic Perfusion Versus Cold Storage in the Setting of Renal Transplantation.

Kidney transplantation (KT) is the most effective treatment for end-stage renal disease. End-ischemic hypothermic machine perfusion (EI-HMP) has emerged as a promising method for preserving grafts before transplantation. This study aimed to compare graft function recovery in KT recipients of deceased brain-death (DBD) grafts preserved with EI-HMP versus static cold storage (SCS). The primary outcome was the rate of delayed graft function (DGF). Secondary outcomes included urine output, intensive care unit (ICU) stay, hospital stay duration, and survival rates. A retrospective, single-center observational study was conducted at Sapienza University of Rome, analyzing 313 KT patients between January 2014 and September 2021. Patients were stratified into two groups based on graft preservation methods (EI-HMP, n = 95; SCS, n = 218). A stabilized inverse probability treatment weighting (IPTW) method was employed to adjust for potential confounders. There were no significant differences in DGF rates between the two groups (17.9% vs. 15.6% in SCS and EI-HMP cases, respectively; p = 0.75). EI-HMP group demonstrated a higher urine output on day 2 (p = 0.046), a shorter ICU stay (p < 0.0001), and a trend toward a shorter overall hospital stay (p = 0.07). No statistically significant differences were found between EI-HMP and SCS cases in 1- and 3-year overall survival rates (3.2% and 6.7% vs. 5.6% and 6.6%, respectively; log-rank p = 0.53) or in death-censored graft loss rates (5.4% and 8.9% vs. 5.7% and 7.3%, respectively; log-rank p = 0.88). In a sub-analysis of expanded criteria donors (ECD), EI-HMP demonstrated a protective effect by reducing the risk of DGF (OR = 0.31, 95% CI = 0.09-0.95; p = 0.047). EI-HMP was associated with certain short-term benefits, including increased urine output and reduced ICU stays, but showed no significant impact on long-term survival outcomes. A reduction in DGF rates was observed only in the ECD subgroup. Randomized controlled trials are necessary to further investigate the long-term clinical benefits of EI-HMP.

Normothermic Machine Perfusion in Orphan Liver Graft Viability Assessment

Normothermic Machine Perfusion in Orphan Liver Graft Viability Assessment

Exploring auxiliary liver transplantation in the era of transplant oncology - A proposal for a new liver splitting program (ALERT-50).

Total hepatectomy and liver transplantation has emerged as a game-changing strategy in the treatment of several liver-confined primary or metastatic tumors, opening the new era of transplant oncology. However, the expansion of indications is going to worsen the chronic scarcity of organs, and new strategies are needed to enlarge the donor pool. A possible source of organs could be developing split liver transplantation (SLT) programs. We propose to refer donors aged 18-50 years unsuitable for pediatric patients and donors aged 50-60 years for split evaluation. This will generate new small left lateral grafts that can be used for RAPID procedures, based on a national waiting list specifically for non-HCC oncologic patients. Centralized imaging review will streamline the donor-recipient matching process and address organizational challenges. Additionally, adopting an ex-situ splitting technique during hypothermic oxygenated machine perfusion could further enhance logistical efficiency and improve graft viability. The proposed protocol (ALERT 50) will therefore promote the development of oncologic indications without affecting the standard waiting list and without competing with urgent or pediatric patients.

Perfusate Liver Arginase 1 Levels After End-Ischemic Machine Perfusion Are Associated with Early Allograft Dysfunction.

Background/Objectives: The rising use of liver grafts from donation after circulatory death (DCD) has been enabled by advances in normothermic regional perfusion (NRP) and machine perfusion (MP) technologies. We aimed to identify predictive biomarkers in DCD grafts subjected to NRP, followed by randomization to either normothermic machine perfusion (NMP) or dual hypothermic oxygenated perfusion (D-HOPE). Methods: Among 57 DCD donors, 32 liver grafts were transplanted, and recipients were monitored for one week post-transplant. Biomarkers linked with oxidative stress, hepatic injury, mitochondrial dysfunction, inflammation, regeneration, and autophagy were measured during NRP, end-ischemic MP, and one week post-transplant. Results: Arginase-1 (ARG-1) levels were consistently higher in discarded grafts and in recipients who later developed early allograft dysfunction (EAD). Specifically, ARG-1 levels at the end of MP correlated with markers of hepatic injury. Receiver operating characteristic analysis indicated that ARG-1 at the end of MP had a good predictive accuracy for EAD (AUC = 0.713; p = 0.02). Lipid peroxidation (TBARS) elevated at the start of NRP, declined over time, with higher levels in D-HOPE than in NMP, suggesting a more oxidative environment in D-HOPE. Metabolites like flavin mononucleotide (FMN) and NADH exhibited significant disparities between perfusion types, due to differences in perfusate compositions. Inflammatory biomarkers rose during NRP and NMP but normalized post-transplantation. Regenerative markers, including osteopontin and hepatocyte growth factor, increased during NRP and NMP and normalized post-transplant. Conclusions: ARG-1 demonstrates strong potential as an early biomarker for assessing liver graft viability during perfusion, supporting timely and effective decision-making in transplantation.

Challenges and opportunities in organ donation after circulatory death.

In recent years, there has been resurgence in donation after circulatory death (DCD). Despite that, the number of organs transplanted from these donors remains low due to concerns about their function and a lack of an objective assessment at the time of donation. This overview examines the current DCD practices and the classification modifications to accommodate regional perspectives. Several risk factors underscore the reluctance to accept DCD organs, and we discuss the modern strategies to mitigate them. The advent of machine perfusion technology has revolutionized the field of DCD transplantation, leading to improved outcomes and better organ usage. With many strategies at our disposal, there is an urgent need for comparative trials to determine the optimal use of perfusion technologies for each donated organ type. Additional progress in defining therapeutic strategies to repair the damage sustained during the dying process should further improve DCD organ utilization and outcomes. However, there remains wide variability in access to DCD donation and transplantation, and organizational efforts should be doubled up with consensus on key ethical issues that still surround DCD donation in the era of machine perfusion.

Machine Perfusion for Liver Transplant: What Are the Challenges?

Machine Perfusion for Liver Transplant: What Are the Challenges?

Normothermic Liver Machine Perfusion At a Large European Center -Real World Outcomes Following 238 Applications.

To report outcomes from routine clinical practice of liver transplantation (LT) following normothermic liver machine perfusion (NLMP) and compare to LT after static cold storage (SCS). NLMP is emerging as a clinical routine in LT as has recently received renewed attention, however outcomes outside of clinical trials are lacking. All adult LT between February 2018 and January 2023 were included. Comprehensive viability assessment was applied during NLMP. Outcomes were compared between NLMP and SCS recipients, as well as benchmark and non-benchmark cases. Of the 332 LT included, 174 underwent NLMP and 158 were transplanted following SCS. Sixty-seven organs were accepted and transplanted only under the premise of NLMP. One-year graft survival for SCS and NLMP recipients was 83.8% vs. 81.3% and 93.4% for benchmark cases in the overall cohort. Total preservation time had no influence on graft survival in the NLMP group but was associated with inferior 1-year graft survival in the SCS group. NLMP usage increased significantly over the duration of the study period, as did the median total preservation time. With increasing NLMP use and longer preservation times, nighttime surgery decreased significantly from 41.9% to 4.2%. Prolonged preservation times ease logistics and enable daytime surgery. The possibility of NLMP offers to expand liver transplantation without negatively affecting outcomes.

Highlights From the 2nd Turin International Workshop on Liver Machine Perfusion.

The 2nd Turin International Workshop on Liver Machine Perfusion took place in Turin, Italy, on November 22, 2024. Leading experts came together to discuss the current applications, limitations, and future directions of this technology, with a primary focus on but not limited to liver transplantation. This report provides a summary of the evidence, insights, and debates shared during the meeting.

A simplified computational liver perfusion model, with applications to organ preservation

Advanced liver preservation strategies could revolutionize liver transplantation by extending preservation time, thereby allowing for broader availability and better matching of transplants. However, developing new cryopreservation protocols requires exploration of a complex design space, further complicated by the scarcity of real human livers to experiment upon. We aim to create computational models of the liver to aid in the development of new cryopreservation protocols. Towards this goal, we present an approach for generating 3D models of the liver vasculature by building upon the space colonization algorithm. Additionally, we introduce the concept of a super lobule which enables a computational abstraction of biological liver lobules. User-tunable parameters allow for vasculatures of varying depth and topology to be generated. In each model, we solve for a common lumped resistance value assigned to the super lobules, allowing the overall physiological blood pressure and flow rate through the liver to be preserved. We demonstrate our approach’s ability to maintain consistency between models of varying depth. Finally, we simulate steady state machine perfusion of the generated models and demonstrate how they can be used to quickly test the effect of different boundary conditions when designing organ preservation protocols.

Real-Time Biomarkers of Liver Graft Quality in Hypothermic Oxygenated Machine Perfusion.

Background: Hypothermic oxygenated machine perfusion has emerged as a strategy to alleviate ischemic-reperfusion injury in liver grafts. Nevertheless, there is limited data on the effectiveness of hypothermic liver perfusion in evaluating organ quality. This study aimed to introduce a readily accessible real-time predictive biomarker measured in machine perfusate for post-transplant liver graft function. Methods: The study evaluated perfusate analytes over a 90-day postoperative period in 26 patients randomly assigned to receive a liver graft following dual hypothermic machine perfusion in a prospective randomized controlled trial. Machine perfusion was consistently conducted end-ischemically for at least 120 min, with real-time perfusate assessment at 30-min intervals. Graft functionality was assessed using established metrics, including Early Allograft Dysfunction (EAD). Results: Perfusate lactate concentration after 120 min of machine perfusion demonstrated significant predictive value for EAD (AUC ROC: 0.841, p = 0.009). Additionally, it correlated with post-transplant peak transaminase levels and extended hospital stays. Subgroup analysis revealed significantly higher lactate accumulation in livers with post-transplant EAD. Conclusions: Liver graft quality can be effectively assessed during hypothermic machine perfusion using simple perfusate lactate measurements. The reliability and accessibility of this evaluation support its potential integration into diverse transplant centers.