Archie WH, Baimas-George M, Haynes N, Kundu S, Peterson K, Wehrle CJ, Huckleberry D, Eskind L, Levi D, Soto JR, Denny R, Casingal V, Cochran A, Rein EH, Vrochides D. Upper limit of normothermic machine preservation of liver grafts from donation after circulatory death yet to be defined. World J Transplant 2025; 15(2): 99170 [DOI: 10.5500/wjt.v15.i2.99170]
Corresponding Author of This Article
William H Archie, MD, Doctor, Division of Adominal Transplant, Department of Surgery, Carolinas Medical Center, 1000 Blythe Blvd, Charlotte, NC 28203, United States. william.archie@atriumhealth.org
Research Domain of This Article
Surgery
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
William H Archie, Maria Baimas-George, Nathanael Haynes, Souma Kundu, Katheryn Peterson, Damien Huckleberry, Lon Eskind, David Levi, Jose R Soto, Roger Denny, Vincent Casingal, Erin H Rein, Dionisios Vrochides, Division of Adominal Transplant, Department of Surgery, Carolinas Medical Center, Charlotte, NC 28203, United States
Chase J Wehrle, Department of Hepato-Pancreato-Biliary/Liver Transplant Surgery, Cleveland Clinic Transplant Research Center, Cleveland, OH 44195, United States
Allyson Cochran, Department of Surgery, Carolinas Center for Surgical Outcomes Science, Carolinas Medical Center, Charlotte, NC 28203, United States
Author contributions: Archie WH, Baimas-George M, Haynes N and Kundu S assisted with literature review and manuscript writing; Peterson K assisted with data abstraction and analysis; Wehrle CJ assisted with study design and data analysis; Huckleberry D, Eskind L, Levi D, Soto JR, Denny R, Casingal V, and Rein EH assisted with data collection, particularly perfusion parameters and donor information; Cochran A performed statistical analysis of all collected data; Vrochides D was the principal investigator assisting in project design, data interpretation and final manuscript writing; all of the authors read and approved the final version of the manuscript to be published.
Institutional review board statement: This project was approved by the Institutional Review Board (IRB00097121).
Informed consent statement: Full waiver of consent was obtained.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Data sharing statement: Our data contains protected health information. Deidentified data can be made available upon request.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: William H Archie, MD, Doctor, Division of Adominal Transplant, Department of Surgery, Carolinas Medical Center, 1000 Blythe Blvd, Charlotte, NC 28203, United States. william.archie@atriumhealth.org
Received: July 15, 2024 Revised: November 7, 2024 Accepted: December 11, 2024 Published online: June 18, 2025 Processing time: 220 Days and 18.9 Hours
Abstract
BACKGROUND
The normothermic machine perfusion pump (NMPP) could shape the future of transplantation. Providing ex-vivo optimization, NMPP attenuates ischemic insult while replenishing energy. An understanding of machine perfusion time (MPT) impact and potential clinical benefits is paramount and necessitates exploration.
AIM
To investigate the relationship between MPT and post-transplant graft function.
METHODS
Retrospective review of the first 50 donation after circulatory death (DCD) grafts preserved using NMPP in a tertiary institution was performed. Essential preservation time points, graft parameters, recipient information, and postoperative outcomes were prospectively recorded. Early allograft dysfunction (EAD), L-Graft7 score and 90-day outcomes were collected for all grafts. The first 20 recipients were allocated into the early group, considered the learning curve population for the center. The subsequent 30 were allocated into the late group. Recipients were also stratified into cohorts depending on MPT, i.e., short (< 8 hours), medium (8-16 hours) and long (> 16 hours).
RESULTS
NMPP operational parameters were not predictive of EAD, L-GrAFT7 or 90-day outcomes. The early group had significantly less MPT and cold ischemia time than the late group (553 minutes vs 850 minutes, P < 0.001) and (127.5 minutes vs 154 minutes, P = 0.025), respectively. MPT had no impact in either group.
CONCLUSION
Increased MPT of DCD liver grafts had no adverse recipient results for the times utilized in this population, indicating its upper limits, likely beyond 24 hours, are not demonstrated within this study. Future studies are necessary to determine whether longer MPT is beneficial or detrimental to graft function and, if the latter, what is the maximum safe duration. Further studies of the effect of normothermic machine perfusion pump duration on long-term outcomes are also needed.
Core Tip: We performed a retrospective study of the first 50 liver transplants at a single-center tertiary institution to determine if there was any observed relationship between machine perfusion time (MPT) and post-transplant graft function for liver grafts from donation after circulatory death (DCD) and found there to be none despite MPT ranging from six up to 24 hours. This leads us to conclude that the pump itself, not duration, provides the benefit to the graft and that we have yet to determine the upper time limit for maintaining DCD livers on pump, if one exists.
Citation: Archie WH, Baimas-George M, Haynes N, Kundu S, Peterson K, Wehrle CJ, Huckleberry D, Eskind L, Levi D, Soto JR, Denny R, Casingal V, Cochran A, Rein EH, Vrochides D. Upper limit of normothermic machine preservation of liver grafts from donation after circulatory death yet to be defined. World J Transplant 2025; 15(2): 99170
Liver transplantation, once doubted as a futile experiment, has evolved into the sole lifesaving treatment for end-stage liver disease[1]. Since the field’s inauspicious inception in the late 1960s, its expansion and impact has only continued to increase. This impressive growth has not been without obstacles, many of them still existing today, including organ shortage challenges and allocation disparities. Efforts to combat such barriers have focused on increasing the deceased donor pool by optimizing expanded criteria offers and marginal organs, particularly in donation after circulatory death (DCD)[2].
The caution and conservatism that circumambient DCD liver transplantation have historically stemmed from higher complication rates when compared with donation after brain death (DBD), including primary nonfunction (PNF), ischemic cholangiopathy, graft loss, and death[3,4]. As such, acceptance criteria for DCD grafts vary widely across the world, leading to general underuse and constraints by limitations of individual donor and recipient characteristics[5]. In particular, cold ischemia time (CIT) has been found to be not only predictive of graft loss, but also of proportionally higher rates of postoperative complications[6-8].
However, the introduction of ex-vivo perfusion technology, hypothermic and more recently normothermic, has been associated with clinical results that demonstrate potential in changing the landscape for DCD allograft procurement practice and utilization. The historical standard for effective liver preservation has previously been singularly dependent on ischemic cold storage (ICS) which exposes the graft to progressive injury and deterioration[9-11]. ICS further impedes functional ex-vivo evaluation of physiology, delaying graft quality assessment via its potential ramifications up until after implantation[12,13]. As a result, ICS, while a solution that prolonged usability of otherwise discarded organs, still faced the race against the clock. Then normothermic machine perfusion emerged, purporting the ability to be unaffected from the time-based limitations of the ICS, and widening the application for DCD allografts[14-18]. The normothermic machine perfusion pump (NMPP) provides procured grafts with oxygenated blood, medicines, and nutrients at normothermia to maintain a nearly physiological equilibrium, while simultaneously measuring temperature, pressure, flow rates, lactate, and other parameters to allow for ex-vivo pre-implantation graft assessment. Evidence from multicenter randomized clinical human trials found that the NMPP was successful at surmounting ICS limitations, demonstrating lower rates of early allograft dysfunction (EAD), ischemic biliary cholangiopathy and increased utilization of DCD organs[19,20].
While the circuit’s impact on organ function has been studied by assessing markers of cellular destruction, or reduction in hepatic synthetic function prior to transplantation, there is limited evidence on the impact of circuit duration. Currently, organ time on the NMPP circuit varies from hours to days[19,21,22]. Early evidence however is promising; ex-vivo livers remaining longer-term on NMPP have a time-based increase in multiple markers of function, though this has yet to be studied in actual post-transplantation patients[23,24]. As such, the aim of this study is to assess the relationship between length of preservation time on the NMPP circuit with graft function in post-transplant patients and whether the longer a graft is on NMPP, the better function it displays when implanted into the recipient.
MATERIALS AND METHODS
A retrospective analysis of all DCD liver grafts procured and preserved using a NMPP (TransMedics®) at a single-center tertiary institution from July of 2022 to March of 2024 were identified using a prospectively maintained data repository. This project was approved by the Institutional Review Board (IRB00097121) and full waiver of consent was obtained. All DCD liver grafts performed at our institution over this time frame were preserved with the NMPP. On the other hand DBD graft allocated to recipients with model for end-stage liver disease (MELD) over 36, portal venous thrombosis (PVT), pressor requirements or undergoing redo transplantation, were also preserved with NMPP. Of note, all of the DBD grafts undergoing NMPP were excluded from this study.
Recipient parameters including but not limited to demographics, MELD at time of transplant, length of stay (LOS), incidence of PNF, and 90-day graft and patient survival were extracted. Recipient liver function tests, international normalized ratio, lactate, platelets and creatinine values from post-transplant day one through seven were abstracted (Table 1). L-Graft7 score, a predictive model for 90-day graft survival, and EAD were calculated for each recipient. The 90-day outcomes including graft loss, mortality, biliary complications, endoscopic retrograde cholangiopancreatography, hepatic artery thrombosis and PVT were also collected to compare short term outcomes among cohorts.
Table 1 Post-transplant laboratories between post-operative day one and post-operative day seven.
Postoperative laboratories
POD1
POD2
POD3
POD4
POD5
POD6
POD7
Total bilirubin (mg/dL)
4.50
3.40
3.30
3.22
3.07
3.09
3.08
Direct bilirubin (mg/dL)
2.80
2.10
2.00
1.91
1.82
1.87
1.78
Aspartate aminotransferase (IU/L)
497.10
251.45
102.63
60.14
47.84
40.86
42.30
Alanine aminotransferase (IU/L)
260.57
248.76
185.96
153.47
125.45
109.10
104.72
International normalized ratio
1.46
1.36
1.33
1.33
1.32
1.32
1.30
Lactate (mmol/L)
1.57
-
-
-
-
-
-
Platelets (10e3/uL)
68.61
65.02
63.55
68.76
71.86
83.84
99.91
Creatinine (mg/dL)
5.98
2.34
4.19
2.10
2.00
1.99
2.00
Pump parameters and biochemic metrics (flows, pressures, utilization of adjuncts, lactate clearance) were also recorded. All transplanted DCD grafts preserved using NMPP had continuous bile production and lactate clearance (lactate < 2 mmol/L). The following procurement and preservation time intervals (Figure 1) were also extracted: (1) Warm ischemia time (WIT), defined as the agonal WIT plus the asystolic WIT. The maximum acceptable agonal phase with donor systolic blood pressure < 80 mmHg was 45 minutes and 60 minutes for the early and late groups, respectively. That was irrespective of the oxygen saturations; (2) CIT, defined as the time from donor cold flushing up to the connection to the NMPP; and (3) Machine perfusion time (MPT). In addition, donor risk index was calculated for each graft.
Figure 1 Definitions of procurement and preservation time intervals in relationship with donation surgical steps (depicted in green).
“Cold” denotes that while on normothermic machine perfusion pump, graft is maintained at normothermia, foregoing prolonged period of cold ischemia time; “rewarming” denotes that graft is not maintained on ice so does not undergo period of true rewarming. AT: Air temperature; CIT: Cold ischemia time; SBP: Systolic blood pressure; WI: Warm ischemia; WIT: Warm ischemia time.
Cohorts
The first 20 recipients were allocated into the early group which was considered the learning curve population for the center. The subsequent 30 recipients were allocated into the late group. In addition, recipients were also stratified into three cohorts depending on the MPT, i.e., short (< 8 hours), medium (8-16 hours) and long (> 16 hours).
Statistical analysis
Descriptive statistics were performed and reported as appropriate to the variable type and distribution of the data. Comparative analysis between two groups was conducted using the χ² or Wilcoxon rank-sum procedure depending on variable type, and analysis between three groups was performed using the Kruskal-Wallis test. Univariate regressions were developed to assess if there were predictors of the L-Graft7 score value. All analyses were performed using Stata Statistical Software v.17 (StataCorp. 2021) and statistical significance was set at P ≤ 0.05.
RESULTS
A total of 50 patients were analyzed over a 20-month period (July 2022 to March 2024). Median L-Graft7 score was 4.3, indicating predicted 4.3% risk of 90-day graft failure, and pump duration was 660 minutes (Table 2). Most grafts remained on pump for 8 hours to 16 hours (55.1%). A total of 11 grafts (22%) required a backtable arterial reconstruction prior to being placed on the circuit, most of which (n = 9) belonged to the late group.
Table 2 Descriptive statistics of recipients and normothermic machine perfusion pump parameters.
Recipient descriptors
n
Median
Range
Age (years)
50
59
33-72
Transplant model for end-stage liver disease
49
26
7-39
Graft descriptors
L-Graft7
50
4.3
1.9-44.0
Donor risk index
50
1.632
1.339-2.735
Preservation descriptors
Machine perfusion time (minutes)
49
660
223-1446
Cold ischemia time (minutes)
48
146
45-241
Warm ischemia time (minutes)
50
29
8-132
The median LOS, defined as days following transplantation until discharge, was 9 days. No patients developed PNF and two patients died within 90 days. The mortalities were due to graft versus host disease and hemorrhagic shock following hepatic artery aneurysm rupture (which was surgically controlled). Of note, after the aneurysmal rupture, the patient underwent re-transplantation but ultimately died from septic shock. The patient with aneurysmal rupture had EAD and an L-Graft7 score of 44%, highest in our study cohort.
None of the parameters studied were found to be predictive of L-Graft7 score in a univariate model (Table 3). However, the beta coefficient among the three MPT groups had a distinct increase, raising the question where improved L-Graft7 metric could be obtained by further extending the NMPP duration. However, that was not proven to be true in subsequent statistical analysis among the 3 cohorts (Table 4). In addition, 4 patients developed EAD, 1 in the early group and 3 in the late group (Table 5). Broken down by MPT cohort, 1 patient with EAD was in the < 8 hours cohort, 2 in the 8-16 hours cohort, and 1 in the 16-24 hours cohort (P = 0.992) (Table 4).
Table 3 Univariate analysis of recipients and normothermia machine perfusion pump parameters.
Recipient and graft descriptors
Beta coefficient
P value
Age (years)
0.012
0.931
Transplant model for end-stage liver disease
0.086
0.627
Time on pump (minutes)
0.005
0.217
Cold ischemia time (minutes)
0.013
0.658
Warm ischemia time (minutes)
-0.036
0.412
< 8 hours
-2.6
0.362
Late group
-1.1
0.667
Machine perfusion time groups
< 8 hours
Reference
8-16 hours
2.1
0.488
16-24 hours
4.1
0.279
Table 4 Comparative analysis of L-GrAFT7, recipient and normothermic machine perfusion pump parameters across machine perfusion time groups, n (%).
Recipient and graft descriptors
< 8 hours (n = 12)
8-16 hours (n = 27)
16-24 hours (n = 10)
P value
LOS (days)
10 (6-42)
9 (6-24)
8 (6-38)
0.363
ICU LOS (days)
3.92 (2.21-25.47)
3.16 (0.16-9.15)
3.12 (0.71-8.08)
0.428
ICU readmission
0 (0)
2 (7.4)
4 (40)
0.009
Age (years)
62.5 (48-72)
57 (33-68)
59 (43-70)
0.227
Transplant model for end-stage liver disease
26.5 (13-39)
25 (7-34)
24 (7-30)
0.890
Machine perfusion time (minutes)
337 (223-458)
722 (510-920)
1154 (995-1446)
0.001
L-GrAFT7
3.9 (1.9-20.1)
5.5 (2-42.8)
4.8 (2.1-44.0)
0.312
Early allograft dysfunction
1 (8.33)
2 (7.41)
1 (8.33)
0.992
Donor risk index
1.62 (1.38-2.03)
1.63 (1.28-2.74)
1.71 (1.34-2.49)
0.670
Cold ischemia time (minutes)
135 (80-219)
153.5 (45-210)
140.5 (94-241)
0.719
Warm ischemia time (minutes)
28 (18-110)
29 (19-132)
29.5 (8-110)
0.970
Table 5 Comparative analysis of L-GrAFT7, recipient and normothermic machine perfusion pump parameters between ‘early’ and ‘late’ groups, n (%).
Recipient and graft descriptors
Early group (n = 20)
Late group (n = 30)
P value
LOS (days)
7.5 (6-42)
10 (6-38)
0.096
ICU LOS (days)
3.4 (0.16-25.5)
3.2 (0.48-10.5)
0.488
ICU Readmission
1 (5)
5 (16.7)
0.214
Age (years)
60.5 (33-72)
58.5 (42-72)
0.779
Transplant model for end-stage liver disease
27 (14-29)
25 (7-39)
0.574
Machine perfusion time (minutes)
553 (256-882)
850 (223-1446)
0.001
L-GrAFT7
3.9 (1.9-42.8)
4.9 (2-44)
0.641
Early allograft dysfunction
1 (5)
3 (10)
0.05
Donor risk index
1.63 (1.44-2.03)
1.63 (1.34-2.74)
0.694
Cold ischemia time (minutes)
127.5 (45-219)
154 (94-241)
0.025
Warm ischemia time (minutes)
29.5 (18-132)
29 (8-110)
0.871
Patients in the early group, had statistically shorter MPT (553 minutes vs 850 minutes, P < 0.001) and CIT (127.5 minutes vs 154 minutes, P = 0.025) times, when compared with the late group (Table 5). The former was due to an increasing "trust" in the efficacy of the NMPP technology, which allowed reliance on longer MPT times. The latter was associated with the higher number of arterial reconstructions in the late group (nine vs two). All arterial reconstructions were completed after donor hepatectomy and prior to normothermic perfusion. Due to this, the 11 reconstructed grafts experienced statistically longer CIT (190.5 minutes vs 142 minutes, P = 0.012), when compared to the 39 non- reconstructed grafts (Table 6).
Table 6 Comparative analysis of normothermic machine perfusion pump parameters between grafts with and without backtable arterial reconstruction.
Perfusion descriptors
No reconstruction (n = 39)
Reconstruction (n = 11)
P value
Machine perfusion time (minutes)
660 (223-1446)
707 (326-1183)
0.967
Cold ischemia time (minutes)
142 (45-241)
190.5 (129-219)
0.012
Warm ischemia time (minutes)
29 (8-132)
27 (12-98)
0.288
Lastly, across all 90-day outcomes there was no significant difference between early and late cohorts (Table 7) nor between the three MPT cohorts (Table 8).
Table 7 Comparative analysis of 90-day outcomes between ‘early’ and ‘late’ groups, n (%).
The introduction of the NMPP has already begun to alter the landscape of liver transplantation, boasting superior results to traditional ICS in randomized controlled trials[20]. An understanding of the limit of benefit from time on pump and its potential impact on short-term and long-term clinical outcomes is now needed to better utilize this new technology. This study, although it has detected a trend, did not reveal a statistically significant positive correlation between incidence of EAD, L-Graft7 score or 90-day outcomes and NMPP duration. However, it also did not lead to compromised graft function at least for the times utilized in this population, denoting that the upper MPT limits have not been reached during this study.
During liver transplantation, a crucial juncture is graft reperfusion due to the significant hemodynamic and metabolic strains it imposes, especially after cold preservation. The resultant stress and injury can directly influence short-term patient outcomes and graft dysfunction[25]. Unfortunately, the pathophysiology of postreperfusion syndrome is complex and yet to be fully elucidated–but is clearly linked to liver ischemia-reperfusion injury[26]. As such, machine perfusion, initially hypothermic and more recently normothermic, has begun as a method to mitigate, and even resuscitate, this damage[27,28]. Providing unremitting graft perfusion with physiologic pressures and nutrient-rich perfusate, the NMPP attenuates the ischemic insult and replenishes graft energy status, subsequently improving patient and graft outcomes[20,22,28].
While studies are beginning to consistently demonstrate the effectiveness and superiority of NMPP to enhance donor liver function, the optimal and safe duration of the NMPP application remains in question. Previous studies have explored the use of grafts with total preservation time up to 24 hours, however, normothermic perfusion time accounted for only up to 18 hours of total preservation time[29]. The PROTECT trial had an average perfusion time of just over 4.5 hours while Chapman et al[30] demonstrated an average normothermic perfusion time of 6 hours[20]. Neither study analyzed any relationship specifically between time on pump and clinical outcomes. This study aimed to initiate such evaluation, observing DCD grafts placed on NMPP and assessing early post-transplant graft function using EAD, predicted graft function with L-Graft7 score, and 90-day outcomes against MPT. Ultimately, although a positive trend was detected for L-Graft7 score specifically, we found that the duration of MPT had no statistically significant correlation with any outcome measure.
In addition, all analyses were also conducted after stratification of grafts into an early, learning curve, cohort, comprising of the first 20 grafts and a late, technical maturity, cohort comprising the subsequent 30 grafts. CIT and MPT were both found to be significantly longer in the late cohort. The longer CIT is easily attributable to the percentage of donor grafts requiring hepatic artery backtable reconstruction. On the other hand, the longer MPT is attributable to changes in practice, since over time, the encouraging results witnessed with the NMPP platform have increased our center’s comfort for keeping grafts on the pump for longer durations. Regardless, we again found that the duration of MPT had no statistically significant correlation with EAD incidence, L-Graft7 score, or 90-day outcomes, neither in the early nor the late cohorts.
Of course, these findings raise the possibility that extending MPT for liver grafts may not offer increased clinical benefit or affect early graft function and that deliberate extension of MPT may be unnecessary. However, it is notable that we observed no decline in post-transplant graft function among stratified MPT groups, even when liver grafts were normothermically perfused for up to 24 hours prior to transplantation. Coupled with the detection of a positive correlation trend between MPT and L-Graft7 score by the univariate analysis described in the results section, it is tempting to assume that we have yet to determine an MPT limit (plateau) up to which a graft can be maintained on the NMPP platform prior to transplantation, or, better yet, that we haven't actually reached the time limit after which NMPP will start yielding statistically detectable improved liver graft function metrics.
If the potential to maintain liver grafts on NMPP for prolonged times without clinical detriment is actually realized, it would have significant implications for graft allocation, usage, and operative planning. Liver transplants could be scheduled to follow one another with additional allografts being maintained on NMPP until staff are available, without worrying about the duration of "pumping". Number of operating rooms, surgeons or anesthesiologists would not hinder facilities capacity to accept grafts, provided long-term graft maintenance on NMPP is feasible. In effect, liver grafts could be procured and stored on NMPP until fully staffed operating room teams and transplant recipients were prepared.
Currently, the NMPP has already expanded the liver donor pool with the increased utilization of marginal grafts, most notably DCDs. It could also have the further potential to increase functional utilization of all available grafts through increased MPT without negative clinical impact on post-transplant graft function. This increased graft availability addresses high waiting list mortality in end-stage liver disease and represents a new opportunity for expanded oncologic indications. Currently, patients with otherwise unresectable liver-only metastatic disease from colorectal or neuroendocrine malignancies have a significant five-year disease-free survival after transplantation, often exceeding 50%[31,32]. However, due to graft scarcity, transplantation for such oncologic indications has not been popularized, particularly in light of a 70% survival benchmark after transplantation for cirrhosis or hepatocellular carcinoma[33,34]. A possible increased availability of acceptable-risk liver grafts using the NMPP with extended MPT may represent a solution for optimizing logistics and lead to more efficient utilization of allografts for extended oncologic purposes.
The limitations of this study include a retrospective design, small sample size, single-center cohort, and the lack of long-term follow-up. We certainly expect the sample size to increase in future studies coming from our center, especially given more permissive criteria of DCD liver allograft acceptance in the setting of NMPP. Also, we are currently collecting long-term, 6-month and 12-month, follow-up data to evaluate the incidence of ischemic cholangiopathy and other late presenting pathology, such as infection and malignancy. We had initially attempted to use EAD as our measure for early graft function, however, due to the low incidence in our study population, we elected to utilize L-Graft7, a validated predictive model for 90-day graft failure as an indicator of early postoperative liver function coupled with 90-day outcomes including graft loss[35,36]. Future studies, ideally multi-institutional prospective, are necessary to verify whether the NMPP has indeed a time-dependent protective effect on the procured allograft, to further explore the time limits of this innovative technology, and to evaluate long-term outcomes.
CONCLUSION
The increased duration of NMPP of DCD liver grafts did not lead to adverse recipient results, denoting that its upper limits have not been reached yet. These limits probably lie above the 24 hours mark. Future studies are necessary to determine whether longer NMPP duration is beneficial (or detrimental) to the graft function and, if the latter, what would be the maximum safe time limit. In addition, studies of the effect of NMPP duration on logistics and long-term outcomes, such as ischemic cholangiopathy, are also needed. Therefore, the ability of the NMPP to achieve graft resuscitation and energy replenishment, coupled with the potential to maintain grafts for extended periods widens the application for marginal allograft use, including increased liver transplant opportunities for expanded oncologic indications. Multi-institutional clinical outcomes research is urgently required for prospective validation of the NMPP protective effects on the procured allograft, as well as for further exploration into the time limits of the platform.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Transplantation
Country of origin: United States
Peer-review report’s classification
Scientific Quality: Grade C
Novelty: Grade B
Creativity or Innovation: Grade B
Scientific Significance: Grade B
P-Reviewer: Brombosz EW S-Editor: Luo ML L-Editor: A P-Editor: Zhang YL
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