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  • Panayotova GG
  • Lunsford KE
  • Quillin RC
  • Rana A
  • Agopian VG
  • et al.
Hepatology. 2024 May 1;79(5):1033-1047 doi: 10.1097/HEP.0000000000000715.
CET Conclusion
Reviewer: Mr John Fallon, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This large open labelled multi-centre randomised control trial is an exciting development in the field of liver HMP. The key strength of this work is that 43% (n=27) of the HMP-O2 livers had continuous perfusion, having been placed on device at the donor. This is the first trial in liver HMP to do this and is an important development. Made possible by Organ Recovery Systems portable Lifeport Liver device, especially considering 81% travelled by air, a current limitation of the portable NMP devices. They demonstrated a nonsignificant reduction in EAD with 11% in HMP-O2 and 16% in SCS, while the finding is not significant it is in keeping with the 5 other published RCTs on HMP liver. The lack of significance may derive from the fact that within the intervention group only 24% were ECDs (including 5 DCD), upon sub-group analysis of these ECDs they find the reduction of EAD to be significant (20% in HMP-O2 and 33.3% in SCS p=0.004). This is in keeping with previous large RCTs that the beneficial effects of HMP-O2 are amplified in the ECD cohort, especially in DCDs seen in Rijn et al’s 2021 trial published in the New England Journal who perfused only DCD livers. None of their secondary outcomes reach significance, but with PNF only occurring in the SCS group with 3 patients and a further 2 (n=5 6.8%) went on to require re-transplant also due to ischaemic cholangiopathy. In HMP-O2 only 1 required retransplant, this was due to HAT. Biliary complications were nearly double in the SCS group (26.4% vs 12.7%) which is impressive, but again this failed to reach significance. The trends are encouraging, but the lack of significance is disappointing, the trial having not been powered for overall EAD rates. An increase cohort size and a focus on EADs could have led to more dramatic results with potentially significance in many of the outcomes. An interesting note is the preservation fluid used in HMP-O2 was Vasosol, a UW-like solution with the addition of nitric oxide donors and vasodilators, this is the first HMP RCT across all organs to utilise this solution and could, in part be responsible for some of the beneficial trends. Unfortunately, the study was not sufficiently powered to compare continuous HMP-O2 with end-ischaemic HMP-O2 and SCS, the overall storage duration being comparable, but the percentage of that time being perfusion obviously being highest in the continuous group. They demonstrate safety and non-inferior efficacy of a novel portable device, which as it becomes more popular and people become more familiar with placing livers on device at retrieval more data should emerge on continuous HMP-O2, this trial was an important step.
Aims: To assess if HMP-O2 improves liver transplant outcomes compare to cold storage.
Interventions: Livers were randomised to intervention, which was HMP-O2 on the Lifeport Liver Transporter device, perfused with Vasosol, or control, which was static cold storage.
Participants: 179 adult whole liver transplant recipients.
Outcomes: The primary outcome was early allograft dysfunction (EAD) as defined by the Olthoff criteria. Secondary outcome measures were PNF, AKI, graft survival, biliary complications. Vascular complications and death. Additional exploratory outcomes were hospital LOS, ICU LOS, lactate clearance, bleeding, incisional hernia and SAEs.
Follow Up: 12 months

In liver transplantation, cold preservation induces ischemia, resulting in significant reperfusion injury. Hypothermic oxygenated machine perfusion (HMP-O 2 ) has shown benefits compared to static cold storage (SCS) by limiting ischemia-reperfusion injury. This study reports outcomes using a novel portable HMP-O 2 device in the first US randomized control trial.


The PILOT trial (NCT03484455) was a multicenter, randomized, open-label, noninferiority trial, with participants randomized to HMP-O 2 or SCS. HMP-O 2 livers were preserved using the Lifeport Liver Transporter and Vasosol perfusion solution. The primary outcome was early allograft dysfunction. Noninferiority margin was 7.5%. From April 3, 2019, to July 12, 2022, 179 patients were randomized to HMP-O 2 (n=90) or SCS (n=89). The per-protocol cohort included 63 HMP-O 2 and 73 SCS. Early allograft dysfunction occurred in 11.1% HMP-O 2 (N=7) and 16.4% SCS (N=12). The risk difference between HMP-O 2 and SCS was -5.33% (one-sided 95% upper confidence limit of 5.81%), establishing noninferiority. The risk of graft failure as predicted by Liver Graft Assessment Following Transplant score at seven days (L-GrAFT 7 ) was lower with HMP-O 2 [median (IQR) 3.4% (2.4-6.5) vs. 4.5% (2.9-9.4), p =0.024]. Primary nonfunction occurred in 2.2% of all SCS (n=3, p =0.10). Biliary strictures occurred in 16.4% SCS (n=12) and 6.3% (n=4) HMP-O 2 ( p =0.18). Nonanastomotic biliary strictures occurred only in SCS (n=4).


HMP-O 2 demonstrates safety and noninferior efficacy for liver graft preservation in comparison to SCS. Early allograft failure by L-GrAFT 7 was lower in HMP-O 2 , suggesting improved early clinical function. Recipients of HMP-O 2 livers also demonstrated a lower incidence of primary nonfunction and biliary strictures, although this difference did not reach significance.

  • Czigany Z
  • Putri AJ
  • Michalski CW
  • Mehrabi A
Hepatology. 2024 Mar 5; doi: 10.1097/HEP.0000000000000811.
  • Tang G
  • Zhang L
  • Xia L
  • Zhang J
  • Wei Z
  • et al.
Int J Surg. 2024 Jan 1;110(1):464-477 doi: 10.1097/JS9.0000000000000784.

Hypothermic oxygenated machine perfusion (HOPE) is a novel organ-preservation technology designed to optimize organ quality. However, the effects of HOPE on morbidity and mortality after liver transplantation remain unclear. This meta-analysis evaluated the potential benefits of HOPE in liver transplantation.


The Embase, Web of Science, PubMed, Cochrane Library, and Scopus databases were searched for articles published up to 15 June 2023 (updated on 12 August 2023). Mean differences (MDs), risk ratios (RRs), and 95% confidence intervals were calculated.


Eleven studies encompassing five randomized controlled trials and six matched studies were included, with a total of 1000 patients. HOPE did not reduce the incidence of major postoperative complications (RR 0.80), primary non-function (PNF) (RR 0.54), reperfusion syndrome (RR 0.92), hepatic artery thrombosis (RR 0.92), renal replacement therapy (RR 0.98), length of hospital stay (MD, -1.38 days), 1-year recipient death (RR 0.67), or intensive care unit stay (MD, 0.19 days) after liver transplantation. HOPE reduced the incidence of biliary complications (RR 0.74), non-anastomotic biliary strictures (NAS) (RR 0.34), early allograft dysfunction (EAD) (RR 0.54), and acute rejection (RR 0.54). In addition, HOPE improved the retransplantation (RR 0.42) and 1-year graft loss rates (RR 0.38).


Compared with static cold storage (SCS), HOPE can reduce the incidence of biliary complications, NAS, EAD, and acute rejection and retransplantation rate after liver transplantation and improve the 1-year graft loss rate. These findings suggest that HOPE, when compared to SCS, can contribute to minimizing complications and enhancing graft survival in liver transplantation. Further research is needed to investigate long-term outcomes and confirm the promising advantages of HOPE in liver transplantation settings.

  • Brouckaert J
  • Dellgren G
  • Wallinder A
  • Rega F
BMJ Open. 2023 Dec 28;13(12):e073729 doi: 10.1136/bmjopen-2023-073729.

Ischaemic cold static storage (ICSS) is the gold standard in donor heart preservation. This ischaemic time frame renders a time constraint and risk for primary graft dysfunction. Cold oxygenated heart perfusion, known as non-ischaemic heart preservation (NIHP), theoretically limits the ischaemic time, while holding on to the known advantage of hypothermia and cardioplegia, a low metabolic rate.


The NIHP 2019 study is an international, randomised, controlled, open, multicentre clinical trial in 15 heart transplantation centres in 8 European countries and includes 202 patients undergoing heart transplantation, allocated 1:1 to NIHP or ICSS. Enrolment is estimated to be 30 months after study initiation. The patients are followed for 12 months after transplantation.The primary objective is to evaluate the effect of NIHP on survival, allograft function and rejection episodes within the first 30 days after transplantation. The secondary objectives are to compare treatment groups with respect to survival, allograft function, cardiac biomarkers, rejection episodes, allograft vasculopathy, adverse events and adverse device effects within 12 months.


This protocol was approved by the Ethics Committee (EC) for Research UZ/KU Leuven, Belgium, the coordinating EC in Germany (Bei Der LMU München), the coordinating EC in the UK (West Midlands-South Birmingham Research), the EC of Hospital Puerta de Hierro, Madrid, Spain, the EC of Göteborg, Sweden, the coordinating EC in France, the EC of Padova, Italy and the EC of the University of Vienna, Austria. This study will be conducted in accordance with current local regulations and international applicable regulatory requirements according to the principles of the Declaration of Helsinki and ISO14155:2020. Main primary and secondary outcomes will be published on modified intention-to-treat population and per-protocol population.



  • Gajate L
  • de la Hoz I
  • Espiño M
  • Martin Gonzalez MDC
  • Fernandez Martin C
  • et al.
JMIR Res Protoc. 2023 Dec 15;12:e50091 doi: 10.2196/50091.

Liver transplantation is the last therapeutic option for patients with end-stage liver disease. Postreperfusion syndrome (PRS), defined as a fall in mean arterial pressure of more than 30% within the first 5 minutes after reperfusion of at least 1 minute, can occur in liver transplantation as a deep hemodynamic instability with associated hyperfibrinolysis immediately after reperfusion of the new graft. Its incidence has remained unchanged since it was first described in 1987. PRS is related to ischemia-reperfusion (I/R) injury, whose pathophysiology involves the release of several mediators from both the donor and the recipient. The antioxidant effect of ascorbic acid has been studied in resuscitating patients with septic shock and burns. Even today, there are publications with conflicting results, and there is a need for further studies to confirm or rule out the usefulness of this drug in this group of patients. The addition of ascorbic acid to preservation solutions used in solid organ transplantation is under investigation to harness its antioxidant effect and mitigate I/R injury. Since PRS could be considered a manifestation of I/R injury, we believe that the possible beneficial effect of ascorbic acid on the occurrence of PRS should be investigated.


The aim of this randomized controlled trial is to assess the benefits of ascorbic acid over saline in the development of PRS in adult liver transplantation.


We plan to conduct a single-center randomized controlled trial at the Hospital Universitario Ramón y Cajal in Spain. A total of 70 participants aged 18 years or older undergoing liver transplantation will be randomized to receive either ascorbic acid or saline. The primary outcome will be the difference between groups in the incidence of PRS. The randomized controlled trial will be conducted under conditions of respect for fundamental human rights and ethical principles governing biomedical research involving human participants and in accordance with the international recommendations contained in the Declaration of Helsinki and its subsequent revisions.


The enrollment process began in 2020. A total of 35 patients have been recruited so far. Data cleaning and analysis are expected to occur in the first months of 2024. Results are expected around the middle of 2024.


We believe that this study could be particularly relevant because it will be the first to analyze the clinical effect of ascorbic acid in liver transplantation. Moreover, we believe that this study fills an important gap in the knowledge of the potential benefits of ascorbic acid in the field of liver transplantation, particularly in relation to PRS.


European Union Drug Regulating Authorities Clinical Trials Database 2020-000123-39; https://tinyurl.com/2cfzddw8; ClinicalTrials.gov NCT05754242; https://tinyurl.com/346vw7sm.



  • DiChiacchio L
  • Goodwin ML
  • Kagawa H
  • Griffiths E
  • Nickel IC
  • et al.
J Surg Res. 2023 Dec;292:222-233 doi: 10.1016/j.jss.2023.07.050.

Heart transplantation is the treatment of choice for end-stage heart failure. There is a mismatch between the number of donor hearts available and the number of patients awaiting transplantation. Expanding the donor pool is critically important. The use of hearts donated following circulatory death is one approach to increasing the number of available donor hearts.


A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines utilizing Pubmed/MEDLINE and Embase. Articles including adult human studies and preclinical animal studies of heart transplantation following donation after circulatory death were included. Studies of pediatric populations or including organs other than heart were excluded.


Clinical experience and preclinical studies are reviewed. Clinical experience with direct procurement, normothermic regional perfusion, and machine perfusion are included. Preclinical studies addressing organ function assessment and enhancement of performance of marginal organs through preischemic, procurement, preservation, and reperfusion maneuvers are included. Articles addressing the ethical considerations of thoracic transplantation following circulatory death are also reviewed.


Heart transplantation utilizing organs procured following circulatory death is a promising method to increase the donor pool and offer life-saving transplantation to patients on the waitlist living with end-stage heart failure. There is robust ongoing preclinical and clinical research to optimize this technique and improve organ yield. There are also ongoing ethical considerations that must be addressed by consensus before wide adoption of this approach.

  • Mulvey JF
  • Shaheed SU
  • Charles PD
  • Snashall C
  • Lo Faro ML
  • et al.
Ann Surg. 2023 Nov 1;278(5):676-682 doi: 10.1097/SLA.0000000000006046.
CET Conclusion
Reviewer: Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This well-written report details an analysis of perfusate samples collected during the COMPARE study, an RCT comparing oxygenated with non-oxygenated machine perfusion. Mass spectrometry was used to analyse the proteomic make up of the perfusate fluid. During hypothermic machine perfusion, proteins enter the perfusate system, increasing over time. The authors explored the relation between perfusate proteins and clinical outcomes, with some indication that outcomes such as acute rejection and kidney function at 12 months.
Aims: The aim of this study was to provide mechanistic insight into biological alterations that occur in deceased donor kidneys during standard nonoxygenated versus oxygenated hypothermic machine perfusion (HMP), using perfusate samples collected in the COMPARE study.
Interventions: In the COMPARE trial, pairs of kidneys donated following circulatory death were randomly assigned to receive either oxygenated HMP or nonoxygenated HMP.
Participants: 210 perfusate samples.
Outcomes: The main outcome of this paper was to identify protein changes across durations of perfusion and in relation to 12-month estimated glomerular filtration rate (eGFR).
Follow Up: 12 months

To provide mechanistic insight into key biological alterations in donation after circulatory death kidneys during continuous pefusion we performed mass spectrometry profiling of perfusate samples collected during a phase 3 randomized double-blind paired clinical trial of hypothermic machine perfusion with and without oxygen (COMPARE).


Despite the clinical benefits of novel perfusion technologies aiming to better preserve donor organs, biological processes that may be altered during perfusion have remained largely unexplored. The collection of serial perfusate samples during the COMPARE clinical trial provided a unique resource to study perfusate proteomic profiles, with the hypothesis that in-depth profiling may reveal biologically meaningful information on how donor kidneys benefit from this intervention.


Multiplexed liquid chromatography-tandem mass spectrometry was used to obtain a proteome profile of 210 perfusate samples. Partial least squares discriminant analysis and multivariate analysis involving clinical and perfusion parameters were used to identify associations between profiles and clinical outcomes.


Identification and quantitation of 1716 proteins indicated that proteins released during perfusion originate from the kidney tissue and blood, with blood-based proteins being the majority. Data show that the overall hypothermic machine perfusion duration is associated with increasing levels of a subgroup of proteins. Notably, high-density lipoprotein and complement cascade proteins are associated with 12-month outcomes, and blood-derived proteins are enriched in the perfusate of kidneys that developed acute rejection.


Perfusate profiling by mass spectrometry was informative and revealed proteomic changes that are biologically meaningful and, in part, explain the clinical observations of the COMPARE trial.

  • Grąt M
  • Morawski M
  • Zhylko A
  • Rykowski P
  • Krasnodębski M
  • et al.
Ann Surg. 2023 Nov 1;278(5):662-668 doi: 10.1097/SLA.0000000000006055.
CET Conclusion
Reviewer: Mr John Fallon, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This small, randomised control trial looked at early post-transplant outcomes after dHOPE compared with SCS in an undifferentiated group of DBD livers. They found no significant difference in their primary outcome of MEAF score between the two groups. They also found no difference in all grades of complications, mortality, post-reperfusion syndrome rates, comprehensive complications index (CCI), L-GrAFT7, or the other non-prespecified secondary outcomes, ITU stay, PNF, EAD and EASE score. The lack of significant benefits were similar to that seen in Schlegal et al’s recent larger multicentre randomised trial who used CCI as their primary outcome. In this study, only 26 livers were in the intervention group and they were hoping to detect a MEAF score reduction of 1.5, a delta in primary outcome of no specific significance. The small number and lack of power calculation has meant there is significant risk of falsely negative findings. They performed a sub-group analysis, dividing the livers arbitrarily by DRI, with a cut-off of >1.7 as becoming ‘high-risk’, within this group dHOPE caused a significant reduction in MEAF score (4.92 vs 6.31, p=0.037) and in CCI (p=0.05). This led the authors to conclude that routine use of dHOPE is not recommended in DBD livers, only for those deemed ‘high-risk’. Again, caution is needed with the conclusion that there is no benefit in lower risk livers, given only 12 and 14 livers were in the DRI ≤1.70 and DRI >1.70 respectively. The trial is appropriately randomised, but was not blinded due to logistical reasons, which with a device trial of this nature is challenging. There is no information given regarding drop-outs or protocol breaches. The area of investigation is interesting and a valid research question, however, this trial is not sufficiently powered to be relied upon as a negative study. They have highlighted a potential difference in benefit, or lack there of depending on the quality of donor, and future studies should consider this and power specifically for sub-group analysis.
Aims: To assess if dual hypothermic oxygenated perfusion (dHOPE) prior to transplantation improves the Model for Early Allograft Function (MEAF) score during the 72 hours following transplant compared with static cold storage (SCS).
Interventions: The intervention group received at least 2 hours of dHOPE prior to transplantation, and the control group underwent standard SCS.
Participants: 104 adult whole liver transplant recipients from donation after brainstem death.
Outcomes: The primary outcome was MEAF score during the 72 hours post transplant. Secondary outcomes were complications over 90-days, 7-day liver graft assessment following transplantation (L-GrAFT7), post-reperfusion syndrome rate, comprehensive complication index (CCI) and mortality.
Follow Up: Not reported

To assess whether end-ischemic hypothermic oxygenated machine perfusion (HOPE) is superior to static cold storage (SCS) in preserving livers procured from donors after brain death (DBD).


There is increasing evidence of the benefits of HOPE in liver transplantation, but predominantly in the setting of high-risk donors.


In this randomized clinical trial, livers procured from DBDs were randomly assigned to either end-ischemic dual HOPE for at least 2 hours or SCS (1:3 allocation ratio). The Model for Early Allograft Function (MEAF) was the primary outcome measure. The secondary outcome measure was 90-day morbidity (ClinicalTrials. gov, NCT04812054).


Of the 104 liver transplantations included in the study, 26 were assigned to HOPE and 78 to SCS. Mean MEAF was 4.94 and 5.49 in the HOPE and SCS groups ( P =0.24), respectively, with the corresponding rates of MEAF >8 of 3.8% (1/26) and 15.4% (12/78; P =0.18). Median Comprehensive Complication Index was 20.9 after transplantations with HOPE and 21.8 after transplantations with SCS ( P =0.19). Transaminase activity, bilirubin concentration, and international normalized ratio were similar in both groups. In the case of donor risk index >1.70, HOPE was associated with significantly lower mean MEAF (4.92 vs 6.31; P =0.037) and lower median Comprehensive Complication Index (4.35 vs 22.6; P =0.050). No significant differences between HOPE and SCS were observed for lower donor risk index values.


Routine use of HOPE in DBD liver transplantations does not seem justified as the clinical benefits are limited to high-risk donors.

  • Chapman WC
  • Barbas AS
  • D'Alessandro AM
  • Vianna R
  • Kubal CA
  • et al.
Ann Surg. 2023 Nov 1;278(5):e912-e921 doi: 10.1097/SLA.0000000000005934.
CET Conclusion
Reviewer: Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This unblinded randomised trial compared the outcomes of liver transplantation following either normothermic machine perfusion (NMP) or static cold storage (SCS). The study employed a ‘device-to-donor’ methodology where the Organox metra device is transported to the site of organ retrieval, which the authors highlight is logistically more challenging. 266 livers were included in the analysis. The primary endpoint was early allograft dysfunction (EAD), defined as abnormal liver parameters 7 days after transplantation. There was no significant difference in EAD between the 2 groups. Although the difference in EAD was numerically greater when using an as treated or sub-group analysis of higher risk groups (high DRI, DCD donor), this to failed to reach statistical significance. The authors reached conclusions similar to that of previous European trials – NMP is a safe modality and shows potential to improve outcomes in marginal organs.
Expert Review
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Clinical Impact Rating 3
Review: The use of machine preservation technologies in liver transplantation has been gaining pace over recent years, with centres using a mixture of normothermic machine perfusion (NMP), hypothermic oxygenated machine perfusion (HOPE) and normothermic regional perfusion (NRP). Machine preservation has the potential to resuscitate the liver, reverse retrieval-related injury, allow longer safe preservation times and enable viability assessment prior to implant. In particular, NMP allows functional assessment of the liver with well-defined parameters predicting early allograft function (1). The first multicentre randomised controlled trial (RCT) of normothermic machine perfusion in Europe was published in 2018, and demonstrated a significant (50%) reduction in the incidence of early allograft dysfunction (EAD) in machine perfused livers, despite longer preservation times (2). These results were replicated in a US study (using a different NMP device), which also demonstrated a significant reduction in the incidence of EAD with NMP (3). Whilst not specifically designed to demonstrate differences in organ utilisation, both studies also showed a reduction in organ discard rates, particularly for donation after cardiac death (DCD) livers. In a recent publication in the Annals of Surgery, Chapman and colleagues report the results of the large multicentre US experience of NMP (4). They used a protocol very similar to that followed in the European RCT. Livers were randomised to either conventional static cold storage (SCS) or NMP, with perfusion initiated at the donor hospital and the liver transported on the device to the implanting centre. In contrast to the European study, the trial did not meet its primary endpoint of demonstrating an overall reduction in EAD. Per-protocol analysis showed similar trends to the prior European and US studies, with greater reduction in EAD rates seen with NMP in DCD and high donor-risk index (DRI) subgroups. Interestingly, there was evidence of a learning curve, with a reduction in EAD rates in the NMP arm following enhanced training during the study. Unlike the previous two RCTs, there was no difference in transplant rate between the arms. One important point to note is that all three RCTs used NMP in a “device-to-donor” configuration, with initiation of NMP at the donor hospital and transport on the device. This has significant logistical challenges, particularly in countries like the US where travel distances are longer and travel by plane is more common. In reality, most centres using NMP routinely in the UK and Europe are using NMP in a “back-to-base” configuration, with transport of the liver under SCS and initiation of perfusion in the recipient centre. Whilst small studies suggest that this does not compromise outcomes for the majority of livers (5), there is no large-scale RCT evidence to support the back-to-base NMP perfusion strategy that many centres are employing. Overall, whilst this study demonstrates a smaller effect size than previous RCTs, it does confirm that the technology is safe and that the main benefit of this technology appears to be for more marginal (high DRI and DCD) livers. References 1. Watson CJE, Gaurav R, Fear C et al. Predicting Early Allograft Function After Normothermic Machine Perfusion. Transplantation 2022; 106: 2391. 2. Nasralla D, Coussios CC, Mergental H et al. A randomized trial of normothermic preservation in liver transplantation. Nature 2018; 557: 50. 3. Markmann JF, Abouljoud MS, Ghobrial RM et al. Impact of Portable Normothermic Blood-Based Machine Perfusion on Outcomes of Liver Transplant: The OCS Liver PROTECT Randomized Clinical Trial. JAMA Surgery 2022; 157: 189. 4. Chapman WC, Barbas AS, D’Alessandro AM et al. Normothermic Machine Perfusion of Donor Livers for Transplantation in the United States - A Randomized Controlled Trial. Annals of Surgery 2023; 5. Ceresa CDL, Nasralla D, Watson CJE et al. Transient Cold Storage Prior to Normothermic Liver Perfusion May Facilitate Adoption of a Novel Technology. Liver Transplantation: Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 2019; 25: 1503.
Aims: The aim of this study was to investigate the effectiveness of normothermic machine preservation (NMP) versus static cold storage (SCS) in the prevention of preservation-related graft injury.
Interventions: Donor livers were randomised to undergo either NMP or SCS.
Participants: 383 donor livers were randomised out of which 266 donor livers were transplanted.
Outcomes: The primary endpoint was early allograft dysfunction (EAD). Secondary endpoints included graft survival, patient survival, incidence of postreperfusion syndrome, biochemical liver function, biliary complications, histological evidence of ischemia-reperfusion injury, feasibility and safety, health economics and organ utilization.
Follow Up: 12 months

To compare conventional low-temperature storage of transplant donor livers [static cold storage (SCS)] with storage of the organs at physiological body temperature [normothermic machine perfusion (NMP)].


The high success rate of liver transplantation is constrained by the shortage of transplantable organs (eg, waiting list mortality >20% in many centers). NMP maintains the liver in a functioning state to improve preservation quality and enable testing of the organ before transplantation. This is of greatest potential value with organs from brain-dead donor organs (DBD) with risk factors (age and comorbidities), and those from donors declared dead by cardiovascular criteria (donation after circulatory death).


Three hundred eighty-three donor organs were randomized by 15 US liver transplant centers to undergo NMP (n = 192) or SCS (n = 191). Two hundred sixty-six donor livers proceeded to transplantation (NMP: n = 136; SCS: n = 130). The primary endpoint of the study was "early allograft dysfunction" (EAD), a marker of early posttransplant liver injury and function.


The difference in the incidence of EAD did not achieve significance, with 20.6% (NMP) versus 23.7% (SCS). Using exploratory, "as-treated" rather than "intent-to-treat," subgroup analyses, there was a greater effect size in donation after circulatory death donor livers (22.8% NMP vs 44.6% SCS) and in organs in the highest risk quartile by donor risk (19.2% NMP vs 33.3% SCS). The incidence of acute cardiovascular decompensation at organ reperfusion, "postreperfusion syndrome," as a secondary outcome was reduced in the NMP arm (5.9% vs 14.6%).


NMP did not lower EAD, perhaps related to the inclusion of lower-risk liver donors, as higher-risk donor livers seemed to benefit more. The technology is safe in standard organ recovery and seems to have the greatest benefit for marginal donors.

  • Liang A
  • Cheng W
  • Cao P
  • Cai S
  • Zhang L
  • et al.
Int J Surg. 2023 Nov 1;109(11):3617-3630 doi: 10.1097/JS9.0000000000000661.

The increasing use of extended criteria donors (ECD) sets higher requirements for graft preservation. Machine perfusion (MP) improves orthotopic liver transplantation (OLT) outcomes, but its effects on different donor types remains unclear. The authors' aim was to assess the effects of hypothermic machine perfusion (HMP), normothermic machine perfusion (NMP), or normothermic regional perfusion (NRP) versus static cold storage (SCS) on different donor types.


A literature search comparing the efficacy of MP versus SCS in PubMed, Cochrane, and EMBASE database was conducted. A meta-analysis was performed to obtain pooled effects of MP on ECD, donation after circulatory death (DCD), and donor after brainstem death.


Thirty nine studies were included (nine randomized controlled trials and 30 cohort studies). Compared with SCS, HMP significantly reduced the risk of non-anastomotic biliary stricture (NAS) [odds ratio (OR) 0.43, 95% confidence interval (CI) 0.26-0.72], major complications (OR 0.55, 95% CI 0.39-0.78), and early allograft dysfunction (EAD) (OR 0.46, 95% CI 0.32-0.65) and improved 1-year graft survival (OR 2.36, 95% CI 1.55-3.62) in ECD-OLT. HMP also reduced primary non-function (PNF) (OR 0.40, 95% CI 0.18-0.92) and acute rejection (OR 0.62, 95% CI 0.40-0.97). NMP only reduced major complications in ECD-OLT (OR 0.56, 95% CI 0.34-0.94), without favorable effects on other complications and survival. NRP lowered the overall risk of NAS (OR 0.27, 95% CI 0.11-0.68), PNF (OR 0.43, 95% CI 0.22-0.85), and EAD (OR 0.58, 95% CI 0.42-0.80) and meanwhile improved 1-year graft survival (OR 2.40, 95% CI 1.65-3.49) in control DCD-OLT.


HMP might currently be considered for marginal livers as it comprehensively improves ECD-OLT outcomes. NMP assists some outcomes in ECD-OLT, but more evidence regarding NMP-ECD is warranted. NRP significantly improves DCD-OLT outcomes and is recommended where longer non-touch periods exist.