Over the past two decades, the application of machine perfusion (MP) in human liver transplantation has moved from the realm of clinical exploration to routine clinical practice. Both in situ and ex situ perfusion strategies are feasible, safe, and may offer improvements in relevant post-transplant outcomes. An important utility of these strategies is the ability to transplant grafts traditionally considered too risky to transplant using conventional cold storage alone. While dynamic assessment and ultimately transplantation of such livers is an important goal for the international liver transplant community, its clinical application is inconsistent. To this end, ELITA (the European Liver and Intestine Transplant Association) gathered a panel of experts to create consensus guidelines regarding selection, approach, and criteria for deceased donor liver assessment in the MP era. An eight-member steering committee (SC) convened a panel of 44 professionals working in 14 countries in Europe and North America. The SC identified topics related to liver utilisation and assessment for transplantation. For each topic, subtopics were created to answer specific clinical questions. A systematic literature review was performed, and the panel graded relevant evidence. The SC drafted initial statements addressing each clinical question. Statements were presented at the in-person Consensus Meeting on Liver Discard and Viability Assessment during the ELITA Summit held from April 19-20, 2024, in Madrid, Spain. Online voting was held to approve statements according to a modified Delphi method; statements reaching ≥85% agreement were approved. Statements addressing liver utilisation, the definition of high-risk livers, and strategies and criteria for dynamic liver assessment are presented.

A common limitation to normothermic ex situ heart perfusion (ESHP) is functional decline. We previously designed a cardioprotective normothermic perfusion protocol, incorporating adenosine-lidocaine cardioplegia, subnormothermic reperfusion, pyruvate and methylprednisolone supplementation, and hemofiltration to prevent myocardial functional decline over 4 hours. In this study, we added continuous catecholamine infusion and protective loading conditions to assess the effectiveness of this enhanced cardioprotective perfusion protocol in preventing functional decline during extended normothermic perfusion in marginal porcine hearts.

Six slaughterhouse pig hearts underwent 9 hours of normothermic ESHP using the enhanced cardioprotective protocol. Cardiac function was assessed at 90, 120, 240, 360, 480 and 540 minutes of ESHP. Subsequently, a preload-challenge was conducted after 9 hours to assess preload-responsiveness (mimicking the Frank-Starling principle) and suitability for transplantation.

During perfusion, myocardial function remained stable, indicated by consistent mean cardiac index (9.2liter/min/kg at 90; 9.3liter/min/kg at 540 minutes of ESHP), left ventricular stroke work index (6,258mmHg*ml/kg at 90; 6,707mmHg*ml/kg at 540 minutes) and rate of ventricular pressure change over time. In response to a preload-challenge, there was a notable increase of 34% in mean cardiac index and 58% in mean stroke work.

Our study demonstrates that the implementation of a cardioprotective protocol enables (very) marginal porcine slaughterhouse hearts, subjected to both a warm and cold ischemic insult prior to ESHP, to sustain satisfactory cardiac function without notable decline during 9 hours of normothermic ESHP, while also preserving their preload-responsiveness. The latter finding might indicate suitability for transplantation. This study provides a groundwork for further extending normothermic ESHP, unlocking the full potential of this promising technology.

Liver transplantation for cancer indications has gained momentum in recent years. This review is intended to optimize the care setting of liver transplant candidates by highlighting current indications, technical aspects and barriers with available solutions to facilitate the guidance of available strategies for healthcare professionals in specialized centres.

A review of the most recent relevant literature was conducted for all the cancer indications of liver transplantation including colorectal cancer liver metastases, hilar cholangiocarcinoma, intrahepatic cholangiocarcinoma, neuroendocrine tumours, hepatocellular carcinoma and hepatic epitheloid haemangioendothelioma.

Transplant benefit from the best available evidence, including SECA I, SECA II, TRANSMET studies for colorectal liver metastases, various preoperative protocols for cholangiocarcinoma patients, standard, extended selection criteria for hepatocellular carcinoma and neuroendocrine tumours, are discussed. Innovative approaches to deal with organ shortages, including machine-perfused deceased grafts, living donor liver transplantation and RAPID procedures, are also explored.

Cancer indications for liver transplantation are here to stay, and the selection criteria among all cancer groups are likely to evolve further with improved prognostication of tumour biology using adjuncts such as radiomics, cancer genomics, and circulating DNA and RNA status. International prospective registry-based studies could overcome the limitations of smaller patient cohorts and lack of level 1 evidence.

Organ preservation plays a critical role in addressing transplantation challenges, including donor shortages and ischemia-reperfusion injury (IRI). Continuous advancements in preservation technologies are essential to meet the increasing demand for transplantable organs. This review provides a comprehensive analysis of organ preservation techniques, spanning from hypothermic storage to advanced methods such as supercooling, vitrification, and partial freezing. Historical milestones, including the development of the EuroCollins, University of Wisconsin (UW), ET-Kyoto, and Celsior solutions, are discussed alongside innovations in machine perfusion and cryopreservation technologies. Particular emphasis is placed on the underlying mechanisms of these techniques, such as metabolic rate suppression, prevention of ice crystal formation, and the application of cryoprotectants, all aimed at extending preservation duration and improving organ quality. Emerging trends, such as the integration of nanotechnology and artificial organ cultivation, are highlighted as promising directions to enhance preservation efficiency. By exploring current advancements and future trends, this review underscores the importance of technological innovation in addressing the global organ shortage crisis and improving transplantation outcomes. STATEMENT OF SIGNIFICANCE: This review offers a comprehensive analysis of the advancements in organ preservation technologies, a critical area in addressing the global organ shortage crisis. By detailing the evolution from early perfusion techniques to cutting-edge innovations like supercooling, vitrification, and nanotechnology, the work underscores the importance of extending organ viability and improving transplant outcomes. Importantly, it bridges historical milestones with emerging trends, showcasing how integration of novel materials and methodologies can revolutionize organ transplantation. This work not only enriches the scientific understanding of organ preservation but also opens pathways for interdisciplinary innovations, setting the stage for the development of sustainable and efficient organ banks. By aligning technological advancements with clinical challenges, it provides actionable insights that could reshape transplantation medicine.

Liver transplantation is the only curative option for end-stage liver disease. Donor shortages necessitate the use of higher risk donor livers, including fatty livers, which are more susceptible to ischemia-reperfusion injury. Machine perfusion has improved graft utilization and is typically performed at hypothermic (8-12°C) or normothermic (35-37°C) temperatures. Here we studied the impact of mild hyperthermia (40°C) as a therapeutic intervention for fatty livers using in-depth proteomic and lipoprotein profiling of whole organ perfusion and precision-cut liver slices. We observed proteomic changes with metabolic alterations over time, evidenced by a significant increase in lipid export in whole organ perfusions. Furthermore, PCLS showed significant upregulation of metabolic processes and heat shock protein response after 24 h of hyperthermia. Machine perfusion under hyperthermic conditions may be a potential strategy to improve the utilization of fatty liver grafts, ultimately expanding the donor pool and improving transplant outcomes.

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 and has recently received renewed attention; however, outcomes outside of clinical trials are lacking.

All adult LT between February 2018 and January 2023 were included. A 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 after 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% versus 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 LT without negatively affecting outcomes.

Coking activities produce high concentrations of aromatic compounds (ACs) and related substances, which may have impacts on human health. However, the health effects of these substances on humans exposed to coking sites have not been fully elucidated. A total of 637 people were recruited to participate in this cross-sectional study. Using multiple linear regression and Bayesian kernel machine regression, we investigated the relationships between the urinary parent or metabolite forms of ACs (including metabolites of PAHs and their derivatives, nitrophenols, and chlorophenols) and hepatorenal biomarkers (HRBs), including total bilirubin, aspartate aminotransferase/alanine aminotransferase, serum uric acid, creatinine, albumin/globulin, and urea. The HRBs adopted in this study can effectively represent the status of human liver and kidney function. Mediation analysis was performed to investigate the possible mediating relationship between ACs and HRBs using oxidative stress markers as mediators. Our study indicated that ACs were significantly associated with increases in TBIL, AST/ALT, A/G, and UA, as well as a significant decrease in Cr. UREA showed no association with ACs among coking workers. The oxidative stress markers 8-hydroxy-2'-deoxyguanosine, 8-iso-prostaglandin-F2α, and 8-iso,15(R)-prostaglandinF2α mediated the induction of ACs on TBIL. Our results suggest that AC exposure in coking workers may be associated with adverse changes in hepatorenal biomarkers. This study highlights the significant impact of ACs from coking activities on workers' hepatorenal biomarkers, providing crucial evidence for health risk assessment and prevention in affected populations.

Ex-situ machine perfusion of the liver has surmounted traditional limitations associated with static cold storage in the context of organ preservation. This innovative technology has changed the landscape of liver transplantation by mitigating ischemia perfusion injury, offering a platform for continuous assessment of organ quality, and providing an avenue for optimizing the use of traditionally marginal allografts. This review summarizes the contemporary clinical applications of machine perfusion devices and discusses potential future strategies for real-time viability assessment, therapeutic interventions, and modulation of organ function after recovery.

Over the past six decades, liver transplantation (LT) has evolved from an experimental procedure into a standardized and life-saving intervention, reshaping the landscape of organ transplantation. Driven by pioneering breakthroughs, technological advancements, and a deepened understanding of immunology, LT has seen remarkable progress. Some of the most notable breakthroughs in the field include advances in immunosuppression, a revised model for end-stage liver disease, and artificial intelligence (AI)-integrated imaging modalities serving diagnostic and therapeutic roles in LT, paired with ever-evolving technological advances. Additionally, the refinement of transplantation procedures, resulting in the introduction of alternative transplantation methods, such as living donor LT, split LT, and the use of marginal grafts, has addressed the challenge of organ shortage. Moreover, precision medicine, guiding personalized immunosuppressive strategies, has significantly improved patient and graft survival rates while addressing emergent issues, such as short-term complications and early allograft dysfunction, leading to a more refined strategy and enhanced post-operative recovery. Looking ahead, ongoing research explores regenerative medicine, diagnostic tools, and AI to optimize organ allocation and post-transplantation car. In summary, the past six decades have marked a transformative journey in LT with a commitment to advancing science, medicine, and patient-centered care, offering hope and extending life to individuals worldwide.

Machine perfusion (MP) is gaining importance in liver transplantation, the only cure for many end-stage liver diseases. Varieties of different MP protocols are available. Currently, various MP protocols are available, differing not only in perfusion temperature but also in the specific perfusion solution required. We aimed to investigate the performance of an HTK-based perfusate during sub-normothermic MP (SNMP) of discarded human liver grafts compared to that of a UW-based solution. Twenty discarded livers (rejected for transplantation by all centers) were subjected to ex-vivo SNMP at 21°C with either HTK- or UW-based solution for 12 h. Perfusate and tissue samples collected before the start, after 6 h, and at the end of SNMP were analyzed for liver enzymes, along with mRNA expression of perfusate and tissue markers associated with organ damage. Hepatocellular viability was assessed by measuring bile production, monitoring pH stability, and analyzing histological changes in HE stained tissue sections. After propensity score matching 16 livers were analyzed. Overall, no differences between HTK- and UW-based solution were detected, except for an increased MLKL mRNA expression and impaired pH stability during SNMP with HTK-based perfusate. No other investigated parameters of cell injury, inflammation or hepatocellular viability supported this finding. Bile production was higher in the 6 HTK-perfused livers compared to the three UW-perfused livers that produced bile. Overall, these findings suggest that HTK performs comparably to a UW-based solution during 12 h of liver SNMP.

The comparison of outcomes in liver transplantation (LT) is hampered by using clinically nonrelevant surrogate endpoints and considerable variability in reported relevant posttransplant outcomes. Such variability stems from nonstandard outcome measures across studies, variable definitions of the same complication, and different timing of reporting. The Clavien-Dindo classification was established to improve the rigor of outcome reporting but is nonspecific to an intervention, and there are unsolved dilemmas specifically related to LT. Core outcome sets (COSs) have been used in other specialties to standardize outcomes research, but have not been defined for LT. Thus, we use the 5 major benchmarking studies published to date to define a 10-measure COS for LT using previously validated metrics. We further provide standard definitions for each of the 10 measures that may be used in international research on the topic. These definitions also include standard time points for recording to facilitate between-study comparisons and future meta-analysis. These 10 outcomes are paired with 3 validated, procedure-independent metrics, including the Clavien-Dindo Classification and the Comprehensive Complications Index. The Clavien scale and Comprehensive Complications Index are specifically reviewed to enhance their utility in LT, and their use, along with the COS, is explored. We encourage future studies to employ this COS along with the Clavien-Dindo grading system and Comprehensive Complications Index to improve the reproducibility and generalizability of research concerning LT.

Hypothermic oxygenated machine perfusion (HOPE) is an organ preservation strategy shown to reduce ischemia-reperfusion injury (IRI)-related complications following liver transplantation. In animal models, HOPE can also decrease alloimmune responses after transplantation, but this remains to be evaluated in humans. Our study, involving 27 patients undergoing liver transplantation enrolled in 2 randomized controlled trials comparing static cold storage with HOPE (14 HOPE-treated and 13 static cold storage-treated), delves into the impact of HOPE on the molecular profile of liver allografts and on the immune responses elicited after transplantation. Following HOPE treatment, fewer intrahepatic immune cells were observed in liver perfusates compared to static cold storage. Analysis of liver tissue transcriptome at reperfusion revealed an effect of HOPE on the reactive oxygen species pathway. Two weeks after transplantation, HOPE recipients exhibited increased circulating CD4+FOXP3+CD127lo regulatory T cells ( p < 0.01), which corresponded to a higher frequency of donor-specific regulatory T cells ( p < 0.01) and was followed by reduced alloreactivity index of CD8+ T cells 3 months after transplant. Our study provides novel mechanistic insight into the capacity of HOPE to influence liver ischemia-reperfusion injury and to modulate effector and regulatory donor-specific T-cell responses after transplantation. These findings, which confirm observations made in animal models, help explain the decreased rejection rates reported in patients receiving HOPE-treated allografts.

The shortage of suitable donor organs has resulted in the use of suboptimal, high-risk, extended-criteria donor (ECD) livers, which are at an increased risk of failure after transplantation. Compared with traditional static cold storage, dynamic preservation by ex situ machine perfusion reduces the risks associated with the transplantation of ECD organs. Ex situ machine perfusion strategies differ in timing (that is, speed of procurement and transport), perfusion duration and perfusion temperature. For 'back-to-base' protocols, the donor liver is statically cold stored during transportation to the recipient hospital (the 'base') and then perfused, instead of transporting the liver using a portable perfusion system. While dual hypothermic (8-12 °C) oxygenated machine perfusion (DHOPE) allows safe prolongation of preservation duration and reduces ischemia-reperfusion injury-related complications, including post-transplant cholangiopathy, normothermic machine perfusion (NMP) at 35-37 °C facilitates ex situ viability testing of both liver parenchyma and bile ducts. Here, we describe a clinical protocol for 'back-to-base' combined DHOPE and NMP, linked by a period of controlled oxygenated rewarming (COR), which we call the DHOPE-COR-NMP protocol. This protocol enables restoration of mitochondrial function after static ischemic preservation and minimizes both ischemia-reperfusion and temperature-shift-induced injury during the start of NMP. The NMP phase allows viability assessment before final donor liver acceptance for transplantation. Sequential DHOPE and COR-NMP may reduce the risks associated with transplantation of ECD livers and facilitate enhanced utilization, thereby helping to alleviate the organ shortage.

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.

Dual hypothermic oxygenated perfusion (DHOPE) is increasingly being used to extend liver preservation to improve transplant logistics. However, little is known about its benefits in high-risk liver grafts. This study aimed to investigate whether prolonged DHOPE provides benefits other than improved logistics in all liver types. We performed a national retrospective cohort study of 177 liver transplants from 12 Italian centers preserved with DHOPE for ≥4 hours between 2015 and 2022. A control group of 177 DHOPEs of <4 hours during the same period was created using 1:1 propensity score matching. The impact of risk profiles and preservation times on the outcomes was assessed using univariable and multivariable regression models. No significant differences in posttransplant outcomes were found between prolonged and short DHOPEs. However, the prolonged group had a significantly lower incidence of posttransplant acute kidney injury (AKI) compared to the short group (30.5% vs. 44.6%, p = 0.008). Among prolonged DHOPEs, no differences in transplant outcomes were observed according to donor risk index, Eurotransplant definition for marginal grafts, and balance of risk score. DHOPE duration was associated with a lower risk of AKI in multivariable models adjusted for donor risk index, Eutrotransplant marginal grafts, and balance of risk score. Prolonged hypothermic oxygenated perfusion confirmed its protective effect against AKI in a multivariable model adjusted for donor and recipient risk factors [OR: 0.412, 95% CI: 0.200-0.850, p = 0.016]. Prolonged DHOPE is widely used to improve transplant logistics, provides good results with high-risk grafts, and appears to be associated with a lower risk of posttransplant AKI. These results provide further insight into the important role of DHOPE in preventing posttransplant complications.

Outcomes after pediatric liver transplantation are generally excellent, but the limited avavailability of suitable, size-matched liver allografts remains a significant barrier. Machine perfusion technology has emerged as a promising approach to expand the donor pool, enabling the use of less ideal whole liver grafts, such as livers donated after circulatory death, and enhancing the execution of split liver transplantation.

This review examines the application of machine perfusion in pediatric liver transplantation, focusing on two primary techniques: hypothermic oxygentaed perfusion and normothermic machine perfusion. These methods optimize storage, resuscitation, and assessment of liver grafts before transplantation, potentially expanding the range of usable donor organs.

The use of machine perfusion allows for the consideration of suboptimal donor livers and facilitates split liver transplantation, both of which could increase organ availability for pediatric patients. Implementation of machine perfusion could also help reduce waiting list mortality by enabling the safe use of a broader spectrum of donor organs.

Adoption of machine perfusion in pediatric liver transplantation will require collaborative, multidisciplinary efforts across transplant centers. By fostering cooperative learning and sharing resources. the integration of machine perfusion into clinical practice has the potential to reduce mortality among children awaiting liver transplantation.

To assess the impact of normothermic machine perfusion (NMP) on patients, medical teams, and costs by gathering global insights and exploring current limitations.

NMP for ex situ liver graft perfusion is gaining increasing attention for its capability to extend graft preservation. It has the potential to transform liver transplantation (LT) from an urgent to a purely elective procedure, which could revolutionize LT logistics, reduce burden on patients and health care providers, and decrease costs.

A 31-item survey was sent to international transplant directors to gather their NMP experiences and vision. In addition, we performed a systematic review on cost-analysis in LT and assessed studies on cost-benefit in converting urgent-to-elective procedures. We compared the costs of available NMPs and conducted a sensitivity analysis of NMP's cost benefits.

Of 120 transplant programs contacted, 64 (53%) responded, spanning North America (31%), Europe (42%), Asia (22%), and South America (5%). Of the total, 60% had adopted NMP, with larger centers (>100 transplants/year) in North America and Europe more likely to use it. The main NMP systems were OrganOx-metra (39%), XVIVO (36%), and TransMedics-OCS (15%). Despite NMP adoption, 41% of centers still perform >50% of LTs at nights/weekends. Centers recognized NMP's benefits, including improved work satisfaction and patient outcomes, but faced challenges like high costs and machine complexity. 16% would invest $100,000 to 500'000, 33% would invest $50,000 to 100'000, 38% would invest $10,000 to 50'000, and 14% would invest <$10,000 in NMP. These results were strengthened by a cost analysis for NMP in emergency-to-elective LT transition. Accordingly, while liver perfusions with disposables up to $10,000 resulted in overall positive net balances, this effect was lost when disposables' cost amounted to >$40,000/organ.

The adoption of NMP is hindered by high costs and operational complexity. Making LT elective through NMP could reduce costs and improve outcomes, but overcoming barriers requires national reimbursements and simplified, automated NMP systems for multiday preservation.

Assess cost and complication outcomes after liver transplantation (LT) using normothermic machine perfusion (NMP).

End-ischemic NMP is often used to aid logistics, yet its impact on outcomes after LT remains unclear, as does its true impact on costs associated with transplantation.

Deceased donor liver recipients at 2 centers (January 1, 2019, to June 30, 2023) were included. Retransplants, splits, and combined grafts were excluded. End-ischemic NMP (OrganOx-Metra) was implemented in October 2022 for extended-criteria donation after brain death (DBDs), all donations after circulatory deaths (DCDs), and logistics. NMP cases were matched 1:2 with static cold storage controls (SCS) using the Balance-of-Risk [donation after brain death (DBD)-grafts] and UK-DCD Score (DCD-grafts).

Overall, 803 transplantations were included, 174 (21.7%) receiving NMP. Matching was achieved between 118 NMP-DBDs with 236 SCS; and 37 NMP-DCD with 74 corresponding SCS. For both graft types, median inpatient comprehensive complications index values were comparable between groups. DCD-NMP grafts experienced reduced cumulative 90-day comprehensive complications index (27.6 vs 41.9, P =0.028). NMP also reduced the need for early relaparotomy and renal replacement therapy, with subsequently less frequent major complications (Clavien-Dindo ≥IVa). This effect was more pronounced in DCD transplants. NMP had no protective effect on early biliary complications. Organ acquisition/preservation costs were higher with NMP, yet NMP-treated grafts had lower 90-day pretransplant costs in the context of shorter waiting list times. Overall costs were comparable for both cohorts.

This is the first risk-adjusted outcome and cost analysis comparing NMP and SCS. In addition to logistical benefits, NMP was associated with a reduction in relaparotomy and bleeding in DBD grafts, and overall complications and post-LT renal replacement for DCDs. While organ acquisition/preservation was more costly with NMP, overall 90-day health care costs-per-transplantation were comparable.

Machine perfusion has been adopted into clinical practice in Europe since the mid-2010s and, more recently, in the United States (US) following approval of normothermic machine perfusion (NMP). We aim to review recent advances, provide discussion of potential future directions, and summarize challenges currently facing the field.

Both NMP and hypothermic-oxygenated perfusion (HOPE) improve overall outcomes after liver transplantation versus traditional static cold storage (SCS) and offer improved logistical flexibility. HOPE offers additional protection to the biliary system stemming from its' protection of mitochondria and lessening of ischemia-reperfusion injury. Normothermic regional perfusion (NRP) is touted to offer similar protective effects on the biliary system, though this has not been studied prospectively.The most critical question remaining is the optimal use cases for each of the three techniques (NMP, HOPE, and NRP), particularly as HOPE and NRP become more available in the US. There are additional questions regarding the most effective criteria for viability assessment and the true economic impact of these techniques. Finally, with each technique purported to allow well tolerated use of riskier grafts, there is an urgent need to define terminology for graft risk, as baseline population differences make comparison of current data challenging.

Machine perfusion is now widely available in all western countries and has become an essential tool in liver transplantation. Identification of the ideal technique for each graft, optimization of viability assessment, cost-effectiveness analyses, and proper definition of graft risk are the next steps to maximizing the utility of these powerful tools.

Hypothermic Oxygenated machine PErfusion (HOPE) has recently emerged as a preservation technique which can reduce ischemic injury and improve clinical outcomes following liver transplantation. First developed with the advent solid organ transplantation techniques, hypothermic machine perfusion largely fell out of favour following the development of preservation solutions which can satisfactorily preserve grafts using the cheap and simple method, static cold storage (SCS). However, with an increasing need to develop techniques to reduce graft injury and better utilise marginal and donation after circulatory death (DCD) grafts, HOPE has emerged as a relatively simple and safe technique to optimise clinical outcomes following liver transplantation. Perfusing the graft with cold, acellular, oxygenated perfusate either via the portal vein (PV) alone, or via both the PV and hepatic artery (HA), HOPE is generally commenced for a period of 1-2 h immediately prior to implantation. The technique has been validated by multiple randomised control trials, and pre-clinical evidence suggests HOPE primarily reduces graft injury by decreasing the accumulation of harmful mitochondrial intermediates, and subsequently, the severity of post-reperfusion injury. HOPE can also facilitate real time graft assessment, most notably via the measurement of flavin mononucleotide (FMN) in the perfusate, allowing transplant teams to make better informed clinical decisions prior to transplantation. HOPE may also provide a platform to administer novel therapeutic agents to ex situ organs without risk of systemic side effects. As such, HOPE is uniquely positioned to revolutionise how liver transplantation is approached and facilitate optimised clinical outcomes for liver transplant recipients.

The shortage of donor organs remains an unresolved issue in livertransplantation worldwide. Consequently, strategies for expanding the donor pool are currently being developed. Donors meeting extended criteria undergo thorough evaluation, as livers obtained from marginal donors yield poorer outcomes in recipients, including exacerbated reperfusion injury, acute kidney injury, early graft dysfunction, and primary nonfunctioning graft. However, the implementation of machine perfusion has shown excellent potential in preserving donor livers and improving their characteristics to achieve better outcomes for recipients. In this review, we analyzed the global experience of using machine perfusion in livertransplantation through the history ofthe development ofthis method to the latest trends and possibilities for increasing the number of liver transplants.