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Background: Primary infection with or reactivation of Epstein- Barr virus (EBV) can occur after liver transplant (LT) and can lead to posttransplant lymphoproliferative disease (PTLD). In pediatric LT, an EBV-DNA viral load (EBV VL) monitoring strategy, including the reduction of immunosuppression, has led to a lower incidence of PTLD. For adult LT recipients with less primary infection and more EBV reactivation, it is unknown whether this strategy is effective. Objective: To examine the effect of an EBV VL monitoring strategy on the incidence of PTLD after LT in adults. Design: Cohort study. Setting: Two university medical centers in the Netherlands. Patients: Adult recipients of first LT in Leiden between September 2003 and January 2017 with an EBV VL monitoring strategy formed the monitoring group (M1), recipients of first LT in Rotterdam between January 2003 and January 2017 without such a strategy formed the contemporary control group (C1), and those who had transplants in Leiden between September 1992 and September 2003 or Rotterdam between 1986 and January 2003 formed the historical control groups (M0 and C0, respectively). Measurements: Influence of EBV VL monitoring on incidence of PTLD. Results: After inverse probability of treatment weighting of the 4 groups to achieve a balance among the groups for important patient characteristics, differences within hospitals between the historical and recent era in cumulative incidences & mdash; expressed as the number of events per 1000 patients measured at 5-, 10-, and 15-year follow-up & mdash;showed fewer events in the contemporary era in both centers. This difference was considerably larger in the monitoring center, whereas the 95% CI included the null value of 0 for point estimates. Limitation: Retrospective, low statistical power, and incompletely balanced groups, and non-EBV PTLD cannot be prevented. Conclusion: Monitoring EBV VL may reduce PTLD incidence after LT in adults; larger studies are warranted.

Objective In the era of organ shortage, redo liver transplantation (reLT) is frequently discussed in terms of expected poor outcome, high cost and therefore wasteful resources. However, there is a lack of benchmark data to reliably assess outcomes after reLT. The aim of this study was to define the ideal reLT case, and to establish clinically relevant benchmark values for best achievable outcome in reLT. Methods We collected data on reLT between January 2010 and December 2018 from 22 high volume transplant centers on three continents. Benchmark cases were defined as recipients with model of end-stage liver disease score Results Out of 1110 reLT 413 (37.2%) qualified as benchmark cases. Benchmark values included: Length of intensive care unit and hospital stay: =3a complications and the CCI at 1 year: Conclusion ReLT remains associated with high morbidity and mortality. The availability of benchmark values for outcome parameters of reLT may serve for comparison in any future analyses of individuals, patient groups, or centers, but also in the evaluation of new therapeutic strategies and principles.

BACKGROUND: With the growing incidence of diabetes mellitus (DM), an increasing number of organ donors with DM can be expected. We sought to investigate the association between donor DM with early post-transplant outcomes.METHODS: From a national cohort of adult liver transplant recipients (1996-2016), all recipients transplanted with a liver from a DM donor (n=69) were matched 1:2 with recipients of livers from non-DM donors (n=138). The primary end-point included early post-transplant outcome, such as the incidence of primary non-function (PNF), hepatic artery thrombosis (HAT), and 90-day graft survival. Cox regression analysis was used to analyze the impact of donor DM on graft failure.RESULTS: PNF was observed in 5.8% of grafts from DM donors versus 2.9% of non-DM donor grafts (p=0.31). Recipients of grafts derived from DM donors had a higher incidence of HAT (8.7% vs. 2.2%, p=0.03) and decreased 90-day graft survival (88.4% [70.9-91.1] vs. 96.4% [89.6-97.8], p=0.03) compared to recipients of grafts from non-DM donors. The adjusted hazard ratio for donor DM on graft survival was 2.21 (1.08-4.53, p=0.03).CONCLUSION: Donor DM is associated with diminished outcome early after liver transplantation. The increased incidence of HAT after transplantation of livers from DM donors requires further research.

Background: Donor hepatectomy time is associated with graft survival after liver transplantation. The aim of this study was to identify the impact of donor hepatectomy time on biliary injury during donation after circulatory death liver transplantation.Methods: First, bile duct biopsies of livers included in (pre)clinical machine perfusion research were analyzed. Secondly, of the same livers, bile samples were collected during normothermic machine perfusion. Lastly, a nationwide retrospective cohort study was performed including 273 adult patients undergoing donation after circulatory death liver transplantation between January 1, 2002 and January 1, 2017. Primary endpoint was development of non-anastomotic biliary strictures within 2 years of donation after circulatory death liver transplantation. Cox proportional-hazards regression analyses were used to assess the influence of hepatectomy time on the development of non-anastomotic biliary strictures.Results: Livers with severe histological bile duct injury had a higher median hepatectomy time (P = .03). During normothermic machine perfusion, livers with a hepatectomy time >50 minutes had lower biliary bicarbonate and bile pH levels. In the nationwide retrospective study, donor hepatectomy time was an independent risk factor for non-anastomotic biliary strictures after donation after circulatory death liver transplantation (Hazard Ratio 1.18 per 10 minutes increase, 95% Confidence Interval 1.06-1.30, P value = .002).Conclusion: Donor hepatectomy time negatively influences histological bile duct injury before normothermic machine perfusion and bile composition during normothermic machine perfusion. Additionally, hepatectomy time is a significant independent risk factor for the development of non-anastomotic biliary strictures after donation after circulatory death liver transplantation. (C) 2020 Elsevier Inc. All rights reserved.

Question What are the outcomes of liver transplants with grafts donated after euthanasia? Findings In this cohort study of 47 liver transplants with grafts donated after euthanasia in the Netherlands and Belgium, recipient and graft survival rates were comparable with the survival rates in a comparative cohort of 542 recipients of liver grafts from donors with a circulatory arrest after the withdrawal of life-supporting treatment. The use of liver grafts donated after euthanasia can expand the pool of grafts donated after circulatory death by approximately 7%. Meaning Findings from this study suggest that the use of liver grafts donated after euthanasia is justifiable and can expand the existing liver donor pool. This cohort study explores the concept, processes, implications, and outcomes of liver organ donation after a donor's death from euthanasia in the Netherlands and Belgium. Importance The option of donating organs after euthanasia is not well known. Assessment of the results of organ transplants with grafts donated after euthanasia is essential to justify the use of this type of organ donation. Objectives To assess the outcomes of liver transplants (LTs) with grafts donated after euthanasia (donation after circulatory death type V [DCD-V]), and to compare them with the results of the more commonly performed LTs with grafts from donors with a circulatory arrest after the withdrawal of life-supporting treatment (type III [DCD-III]). Design, Setting, and Participants This retrospective multicenter cohort study analyzed medical records and LT data for most transplant centers in the Netherlands and Belgium. All LTs with DCD-V grafts performed from the start of the donation after euthanasia program (September 2012 for the Netherlands, and January 2005 for Belgium) through July 1, 2018, were included in the analysis. A comparative cohort of patients who received DCD-III grafts was also analyzed. All patients in both cohorts were followed up for at least 1 year. Data analysis was performed from September 2019 to December 2019. Exposures Liver transplant with either a DCD-V graft or DCD-III graft. Main Outcomes and Measures Primary outcomes were recipient and graft survival rates at years 1, 3, and 5 after the LT. Secondary outcomes included postoperative complications (early allograft dysfunction, hepatic artery thrombosis, and nonanastomotic biliary strictures) within the first year after the LT. Results Among the cohort of 47 LTs with DCD-V grafts, 25 organ donors (53%) were women and the median (interquartile range [IQR]) age was 51 (44-59) years. Among the cohort of 542 LTs with DCD-III grafts, 335 organ donors (62%) were men and the median (IQR) age was 49 (37-57) years. Median (IQR) follow-up was 3.8 (2.1-6.3) years. In the DCD-V cohort, 30 recipients (64%) were men, and the median (IQR) age was 56 (48-64) years. Recipient survival in the DCD-V cohort was 87% at 1 year, 73% at 3 years, and 66% at 5 years after LT. Graft survival among recipients was 74% at 1 year, 61% at 3 years, and 57% at 5 years after LT. These survival rates did not differ statistically significantly from those in the DCD-III cohort. Incidence of postoperative complications did not differ between the groups. For example, the occurrence of early allograft dysfunction after the LT was found to be 13 (31%) in the DCD-V cohort and 219 (45%) in the DCD-III cohort. The occurrence of nonanastomotic biliary strictures after the LT was found to be 7 (15%) in the DCD-V cohort and 83 (15%) in the DCD-III cohort. Conclusions and Relevance The findings of this cohort study suggest that LTs with DCD-V grafts yield similar outcomes as LTs with DCD-III grafts; therefore, grafts donated after euthanasia may be a justifiable option for increasing the organ donor pool. However, grafts from these donations should be considered high-risk grafts that require an optimal donor selection process and logistics.

textabstractDue to the growing number of liver transplantations (LTs), there is an increasing number of patients requiring retransplantation (reLT). Data on the use of grafts from extended criteria donors (ECD), especially donation after circulatory death (DCD), for reLT are lacking. We aimed to assess the outcome of patients undergoing reLT using a DCD graft in the Netherlands between 2001 and July 2018. Propensity score matching was used to match each DCD-reLT with three DBD-reLT cases. Primary outcomes were patient and graft survival. Secondary outcome was the incidence of biliary complications, especially nonanastomotic strictures (NAS). 21 DCD-reLT were compared with 63 matched DBD-reLTs. Donors in the DCD-reLT group had a significantly lower BMI (22.4 vs. 24.7 kg/m2, P-value = 0.02). Comparison of recipient demographics and ischemia times yielded no significant differences. Patient and graft survival rates were comparable between the two groups. However, the occurrence of nonanastomotic strictures after DCD-reLT was significantly higher (38.1% vs. 12.7%, P-value = 0.02). ReLT with DCD grafts does not result in inferior patient and graft survival compared with DBD grafts in selected patients. Therefore, DCD liver grafts should not routinely be declined for patients awaiting reLT.

BACKGROUND: To identify the best possible outcomes in liver transplantation from donation after circulatory death donors (DCD) and to propose outcome values, which serve as reference for individual liver recipients or patient groups.METHODS: Based on 2219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1012 low-risk, primary, adult liver transplantations with a laboratory MELD of ≤20points, receiving a DCD liver with a total donor warm ischemia time of ≤30minutes and asystolic donor warm ischemia time of ≤15minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the Comprehensive Complication Index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75th-percentile was considered.RESULTS: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centers. The one-year retransplant and mortality rate was 5.23% and 9.01%, respectively. Within the first year of follow-up, 51.1% of recipients developed at least one major complication (≥Clavien-Dindo-Grade-III). Benchmark cut-offs were ≤3days and ≤16days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade-III), ≤16.8% for ischemic cholangiopathy, and ≤38.9CCI points at one-year posttransplant. Comparisons with higher risk groups showed more complications and impaired graft survival, outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk.CONCLUSIONS: Despite excellent 1-year survival, morbidity in benchmark cases remains high with more than half of recipients developing severe complications during 1-year follow-up. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups, and provide a valid comparator cohort for future clinical trials.LAY SUMMARY: The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2219 liver transplantations following controlled DCD donation in 17 centres worldwide. The following benchmark cut-offs for the most relevant outcome parameters were developed: ICU and hospital stay: ≤3 and ≤16 days; primary non function: ≤2.5%; renal replacement therapy: ≤9.6%; ischemic cholangiopathy: ≤16.8% and anastomotic strictures ≤28.4%. One-year graft loss and mortality were defined as ≤14.4% and 9.6%, respectively. Donor and recipient combinations with higher risk had significantly worse outcomes. The use of novel organ perfusion technology achieved similar, good results in this high-risk group with prolonged donor warm ischemia time, when compared to the benchmark cohort.

This multicentric study of 17 high-volume centers presents 12 benchmark values for liver transplantation. Those values, mostly targeting markers of morbidity, were gathered from 2024 "low risk" cases, and may serve as reference to assess outcome of single or any groups of patients.To propose benchmark outcome values in liver transplantation, serving as reference for assessing individual patients or any other patient groups.Best achievable results in liver transplantation, that is, benchmarks, are unknown. Consequently, outcome comparisons within or across centers over time remain speculative.Out of 7492 liver transplantation performed in 17 international centers from 3 continents, we identified 2024 low risk adult cases with a laboratory model for end-stage liver disease score ≤20 points, a balance of risk score ≤9, and receiving a primary graft by donation after brain death. We chose clinically relevant endpoints covering intra- and postoperative course, with a focus on complications graded by severity including the complication comprehensive index (CCI). Respective benchmarks were derived from the median value in each center, and the 75 percentile was considered the benchmark cutoff.Benchmark cases represented 8% to 49% of cases per center. One-year patient-survival was 91.6% with 3.5% retransplantations. Eighty-two percent of patients developed at least 1 complication during 1-year follow-up. Biliary complications occurred in one-fifth of the patients up to 6 months after surgery. Benchmark cutoffs were ≤4 days for ICU stay, ≤18 days for hospital stay, ≤59% for patients with severe complications (≥ Grade III) and ≤42.1 for 1-year CCI. Comparisons with the next higher risk group (model for end stage liver disease 21-30) disclosed an increase in morbidity but within benchmark cutoffs for most, but not all indicators, while in patients receiving a second graft from 1 center (n = 50) outcome values were all outside of benchmark values.Despite excellent 1-year survival, morbidity in benchmark cases remains high with half of patients developing severe complications during 1-year follow-up. Benchmark cutoffs targeting morbidity parameters offer a valid tool to assess higher risk groups.