Primary Nonfunction Research Articles

Where are we today with machine perfusion of liver in donation after circulatory death liver transplantation?

Livers procured from donors after circulatory death (DCD) have increasingly been used for liver transplantation (LT) to address the organ crisis. While DCD LT increases patient access to life-saving treatment, this practice creates risks for recipients, including primary allograft non-function, early allograft dysfunction, and ischemic cholangiopathy. These complications are due to the unique ischemia and reperfusion injury related to different phases of organ procurement and preservation in DCD. Therefore, substantial research efforts and innovations on DCD LT have primarily aimed at reducing these complications. One such advance is the utilization of ex vivo machine perfusion of the donor liver in DCD LT. This review focused on the data from clinical trials and studies in human DCD LT.

Effect of creatinine metrics on outcome after transplantation of marginal donor kidneys.

Predicting outcome after transplantation of marginal kidneys is a challenging task. Donor creatinine or estimated glomerular filtration rate (eGFR) are integral components of the respective risk scores. However, there is uncertainty on which of their values obtained successively during procurement is the most suitable. This is a retrospective study of 221 adult brain death donors with marginal kidneys, transplanted in 223 recipients. We applied logistic regression analysis to investigate the association between initial (at hospital admission), nadir (lowest), zenith (highest) and terminal (at recovery) donor eGFR with primary non-function (PNF), delayed graft function (DGF), 3- and 12-month graft function and 1- and 3-year patient- and death-censored graft survival. In the multivariate analysis, admission, terminal, and the lowest donor eGFR could most accurately predict DGF. The respective ORs [95% CI] were: 0.875 [0.771-0.993], 0.818 [95% CI: 0.726-0.922] and 0.793 [0.689-0.900]. Although not being significant for DGF (OR 0.931 [95% CI: 0.817-1.106]), the highest eGFR was the best predictor of 3-month graft function (adjusted b coefficient 1.161 [95% CI: 0.355-1.968]). Analysis of primary nonfunction showed that determination of initial and the highest eGFR proved to be the best predictors. The respective ORs [95% CI] were: 0.804 [0.667-0.968] and 0.750 [0.611-0.919]. There were no differences in the risk associations of each of the four eGFR recordings with patient- and graft survival. The various eGFR recordings determined during the procurement process of marginal donors can predict PNF, DGF and 3- and 12-month graft function. Regarding short-term patient- and graft survival, there appears to be impacted by recipient factors rather than donor kidney function.

Comparison of Three Inferior Vena Cava Reconstruction Techniques in Adult Orthotopic Liver Transplantation: Result From King Chulalongkorn Memorial Hospital, Thailand

BackgroundIn orthotopic liver transplantation (OLT), 3 caval reconstruction techniques are being performed worldwide. These are conventional, piggyback technique, and side-to-side cavocaval anastomosis (CCA). Each has its own advantages and drawbacks. Herein we report the result from our hospital comparing the 3 techniques. MethodsWe retrospectively reviewed the detail of OLT performed from January 2008 to March 2020. Data being collected included type of caval reconstruction, blood loss, operative time, ischemic time, length of stay in the intensive care unit (ICU) and total hospital stay, and several postoperative complications. ResultsIn the given period, 11 conventional, 90 piggyback, and 113 CCA caval reconstruction were done. There were no statistically significant differences in blood loss, operative time, cold ischemic time, and length of ICU and hospital stay. The CCA group had the lowest warm ischemic time (40 minutes) followed by the piggyback technique (43 minutes) and the conventional technique (47 minutes; P < .001). Regarding postoperative complications, there were no statistically significant differences in rate of primary nonfunction, early allograft dysfunction, hepatic artery/portal vein/biliary complication, or rate of acute kidney injury. The hepatic venous outflow complication rate was indifferent between 3 groups. ConclusionsThe present study showed no difference in outflow obstruction rate among the 3 techniques. The choice for reconstruction should rely on the preference of each institute and the suitability of each patient. The CCA technique may provide the lowest warm ischemic time.

344.1: C-Reactive Protein and Urea Levels Distinguish Primary Non-function From Early Allograft Dysfunction After Liver Transplantation

Introduction: A spectrum of graft dysfunction occurs after liver transplantation (LT), ranging from early allograft dysfunction (EAD) to primary non-function (PNF). There are no single or uniformly accepted laboratory parameters that differentiate these entities. Several biochemical markers are exclusively made in the liver, including urea, C-reactive protein (CRP) and fibrinogen. However, these are given les prominence than transaminases, bilirubin and International Normalised Ratio (INR). The aim of this study was to determine if routinely measured serum biochemical markers can distinguish PNFfrom EAD in the initial 48 hours following deceased donor liver transplantation. Methods: A retrospective study of all adult patients that underwent LTat our institution between January 2010 and April 2020 was performed. Patients that experienced graft loss from a complication other than PNF in the initial 14 days were excluded. Patients were grouped into an immediate graft function (IGF), EAD, and a PNF groups. The absolute values and trends of CRP, blood urea, serum transaminases, INR and fibrinogen in the initial post-operative 48 hours were compared between groups. Biochemical factors found to be significantly different between groups on univariable analysis were further investigated using receiver operating characteristic (ROC) curves. The area under the receiver operating characteristic curve (AUROC) value was reported, and the Youden index was used to identify the optimum cut-off values. Results: During the study period, 2102 LTs were performed and 1937 were eligible for inclusion. There were 1394 patients with IGF (72%), 503 with EAD (26%) and 40 with PNF (2%) patients according to the study definition. A significantly greater proportion of grafts were from donors following cardiac death (DCD) in the PNF group compared to the EAD group (45% vs. 29%; p=0.04). The median (IQR) of each variable and the accuracy in distinguishing PNF from EAD is demonstrated in table 1 and 2 respectively. Lack of an increment in CRP (Day 2:1; 1.43 v 1.77, P=0.01) and urea production between on day 1 and 2 (Day 2:1; 0.71 vs 1.32, P=<0.01). The CRP level was significantly lower in the group that experienced PNF on both day 1 and 2 (Day 1; 20 v 43, P=<0.01, Day 2: 24 v 47, p=<0.01,). Urea production was significantly lower on post-operative day 2 in the PNF group (Day 2; 5.1 v 9.0, p=<0.01). An aspartate transaminase (AST) threshold of 2409 IU/L on post operative day 2 had the highest accuracy in distinguishing PNF from EAD (AUC; 0.83, Sensitivity: 81.3%, Specificity 81.4%). Discussion: CRP and AST are more effective than ALT and bilirubin in distinguishing PNF from EAD in the initial post operative 48 hours. Clinicians should consider the values of these markers when making treatment decisions for patients with early liver allograft dysfunction.

P9.16: Validating Survival Scores Following Liver Re-Transplantation, At a Single Center

Introduction: Liver re-transplantation (reTx) is the only therapeutic option for irreversible liver-graft failure, with a reported frequency between 3 and 24%. A strict patient selection is mandatory due to the high risk of the procedure. Our aims were to: 1) evaluate the prevalence and outcomes of reTx at our centre; 2) identify survival predictor factors, validating reported mortality predictor scores for urgent, early and late reTx. Patients and Methods: From July 1995 to March 2022, 1001 consecutive adult liver transplants were performed at our center. Demographical and clinical variables, second graft survival and survival predictor scores (Rosen modified, UCLA and Markmann) were retrospectively applied and analysed for urgent, early and late reTx (2nd and 3rd reTx were excluded). Urgent reTx (U-reTx) was defined as those done within 7 days, early reTx (E-reTx) between 8 and 30 post-operative days, late re-Tx (L-reTx) those that occur after. Statistics: univariate and multivariate analysis, logistic regression for mortality, using ROC curves. Kaplan Meier and log rank for actuarial survival were performed in SPSS v20.0. Results: Sixty-nine reTx (6.8%) were done; mean age was 39±17 years; 58% males. Five (8%) were U-reTx, eight (11%) were E-reTx and 56 (81%) were L-reTx. The mean time between primary LTx (p-LTx) and U-reTx and E- reTx was 4±2 and 26±14 days, respectively and 2016±240 days between p-LTx and L-reTx. Main causes for U-reTx were arterial thrombosis (AT) =3 and primary non function (PNF) =2, causes for E-reTx were AT =5 and PNF =3. L-reTx was indicated due to recurrence disease: 15 (HCV 9, HBV 2, and HAI 4), ductopenic rejection=15, biliary complications= 10, Ischemic cholangiopathy = 9, AT=7. Mean donor age was 35±13 year. Two variables were found to be independently associated with poor outcome, recipient age >45 years (odds ratio 4.1, 95% CI 1.5 to 11.4; p=0.006), and cold ischemia time (CIT) >495 minutes (odds ratio 4.4, 95% CI 1.4 to 13.3; p=0.009). Overall, U-reTx, E-reTx and L-reTx graft and patient survivals at 1, 5 and 7 years are shown in figure 1, as well as those with p-LTx. Markmann survival score was the most sensitive and specific in our cohort (Figure 2).Conclusions: Liver reTx has become an option for patients with early and late graft failure. Recipient age >45 and CIT > 495 minutes were associated with worse outcome. Markmann predicting score was the most useful tool to predict poor outcome in our cohort.

Normothermic liver machine perfusion as a dynamic platform for regenerative purposes: What does the future have in store for us?

Liver transplantation has become an immense success; nevertheless, far more recipients are registered on waiting lists than there are available donor livers for transplantation. High-risk, extended criteria donor livers are increasingly used to reduce the discrepancy between organ demand and supply. Especially for high-risk livers, dynamic preservation using machine perfusion can decrease post-transplantation complications and may increase donor liver utilisation by improving graft quality and enabling viability testing before transplantation. To further increase the availability of donor livers suitable for transplantation, new strategies are required that make it possible to use organs that are initially too damaged to be transplanted. With the current progress in experimental liver transplantation research, (long-term) normothermic machine perfusion may be used in the future as a dynamic platform for regenerative medicine approaches, enabling repair and regeneration of injured donor livers. Currently explored therapeutics such as defatting cocktails, RNA interference, senolytics, and stem cell therapy may assist in the repair and/or regeneration of injured livers before transplantation. This review will provide a forecast of the future utility of normothermic machine perfusion in decreasing the imbalance between donor liver demand and supply by enabling the repair and regeneration of damaged donor livers.

Machine Perfusion as "Comfort Zone": What Are Key Challenges of Liver Viability Assessment Today?

Machine Perfusion as "Comfort Zone": What Are Key Challenges of Liver Viability Assessment Today?

Incidence of Ischemia Reperfusion Injury Related Biliary Complications in Liver Transplantation: Effect of Different Types of Donors

Liver transplantation from donors after circulatory death (DCD) is associated with considerable rates of primary nonfunction and ischemic-type biliary lesions. Compared with donation was after brain death (DBD), the biggest disadvantage of DCD is warm ischemia injury in the procurement stage. Donation after brain death followed by circulatory death (DBCD) is a unique practice in China. Such donors should donate according to the DCD procedure, that is, remove life support and donate after cardiac arrest. We retrospectively analyzed donor and recipient characteristics with preoperative and postoperative parameters according to 3 donation types to comprehensively describe incidence of ischemia reperfusion injury (IRI) related biliary complications among different donor type adult liver transplantation recipients. A total of 50 patients were included in this study (DBD group n=17, DCD group n=26, DBCD group n=7). Only 1 patient, whose donor type was DBCD was diagnosed with ischemic-type biliary lesions demonstrated cast and retrograde ascending cholangitis. Rates of primary graft non-function (DBD n=1, 5.9%; DCD n=2, 7.7%; DBCD, 0%; P=.546) were similar and total biliary complications (DBD n=1, 5.9%; DCD n=1, 3.8%; DBCD N=2, 28.6%; P=.042) were different. No differences were found regarding development of postreperfusion syndrome or coagulopathy in 3 groups. Compared with standard DBD donor, the clinical outcome of DCD donor liver transplantation was satisfactory, with no increase in the incidence of IRI, and, no difference in the incidence of ischemic bile duct complications. This work was carried out in compliance with the Helsinki Congress and the Declaration of Istanbul.

Novel Benchmark Values for Redo Liver Transplantation: Does the Outcome Justify the Effort?

To define benchmark cutoffs for redo liver transplantation (redo-LT). In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT. We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers. Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI ® at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks. This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.

Salvage of Declined Extended-criteria DCD Livers Using In Situ Normothermic Regional Perfusion

This study investigates whether liver grafts donated after circulatory death (DCD) that are declined by the entire Eurotransplant region can be salvaged with abdominal normothermic regional perfusion (aNRP). aNRP is increasingly used for DCD liver grafts because it prevents typical complications. However, it is unclear whether aNRP is capable to rescue pretransplant declined liver grafts by providing the opportunity to test function during donation. Donor livers from DCD donors, declined by all centers in the Eurotransplant region, were included for this study. The comparator cohort included standard DCD livers and livers donated after brain death, transplanted in the same time period. After the withdrawal of life-sustaining treatment, 28 from the 43 donors had a circulatory death within 2 hours, in which case aNRP was initiated. Of these 28 cases, in 3 cases perfusion problems occurred, 5 grafts were declined based on liver assessment, and 20 liver grafts were transplanted. The main differences during aNRP between the transplanted grafts and the assessed nontransplanted grafts were alanine transaminase levels of 53U/L (34-68U/L) versus 367U/L (318-488U/L) ( P =0.001) and bile production in 100% versus 50% of the grafts ( P =0.024). The 12-month graft and patient survival were both 95%, similar to the comparator cohort. The incidence of ischemic cholangiopathy was 11%, which was lower than in the standard DCD cohort (18%). aNRP can safely select and thus is able to rescue DCD liver grafts that were deemed unsuitable for transplantation, while preventing primary nonfunction and minimizing ischemic cholangiopathy.

How Old Is Old? An Age-Stratified Analysis of Elderly Liver Donors above 65.

In liver transplantation, older donor age is a well-known risk factor for dismal outcomes, especially due to the high susceptibility of older grafts to ischemia-reperfusion injury. However, whether the factors correlating with impaired graft and patient survival following the transplantation of older grafts follow a linear trend among elderly donors remains elusive. In this study, liver transplantations between January 2006 and May 2018 were analyzed retrospectively. Ninety-two recipients of grafts from donors ≥65 years were identified and divided into two groups: (1) ≥65–69 and (2) ≥ 70 years. One-year patient survival was comparable between recipients of grafts from donors ≥65–69 and ≥70 years (78.9% and 70.0%). One-year graft survival was 73.1% (donor ≥65–69) and 62.5% (donor ≥ 70), while multivariate analysis revealed superior one-year graft survival to be associated with a donor age of ≥65–69. No statistically significant differences were found for rates of primary non-function. The influence of donor age on graft and patient survival appears not to have a distinct impact on dismal outcomes in the range of 65–70 years. The impact of old donor age needs to be balanced with other risk factors, as these donors provide grafts that offer a lifesaving graft function.

Children undergoing early liver re-transplantation for primary non-function have improved survival.

Primary non-function (PNF) in the early post-LT period in children leads to prolonged hospitalization, high graft loss, and significant mortality. However, there is a paucity of data available on the natural history of children relisted for LT due to PNF, including those who recover graft function and survive with their original allograft. We interrogated the United Network of Organ Sharing (UNOS) database for pediatric LT recipients who were relisted with a primary diagnosis of PNF from 2000 to 2020. Patients >21-year-old and multiple organ transplants were excluded. Logistic regression and Cox proportional hazard models were employed to identify risk factors for early re-transplantation (within 30 days of relisting) and mortality after adjusting for baseline clinical characteristics. One hundred and eight patients were relisted for LT for PNF during the study period. Twenty-five patients survived beyond 30 days from relisting with their original LT, 76 underwent early re-transplantation, and 7 did not survive. Having a high-risk EBV mismatch (OR 2.03, 95% CI 0.66-6.27) and an elevated donor serum creatinine (OR: 2.19, 95% CI 0.54-8.84) were associated with increased odds of a patient requiring early re-transplantation. Donor characteristics including age, final total bilirubin, final AST/ALT, and final serum sodium, as well as vasopressor use prior to procurement, were not associated with increased odds of early re-transplantation (p> 0.05). Operative characteristics including allograft type and cold-ischemia time were also not associated with early re-transplantation (p> 0.05). Patients undergoing early re-transplantation showed a trend toward improved 1-year graft survival (69% vs 55%, p= 0.24). On multivariable Cox proportional hazards modeling, early re-transplantation was associated with reduced risk of overall patient mortality compared to those who survived with their original LT (HR 0.27, 95% CI 0.12-0.67). Early re-transplantation for PNF is associated with improved patient survival compared with patients who survive with their original LT.

Continuous Renal Replacement Therapy in Pediatric Patients With Acute Kidney Injury After Liver Transplantation.

ObjectiveThis study aimed to explore the clinical application of continuous renal replacement therapy (CRRT) in pediatric patients with acute kidney injury (AKI) after liver transplantation.MethodsPediatric patients who underwent liver transplantation were retrospectively investigated. Those who developed AKI within 1 year after the surgery were included and divided into a CRRT group and a non-CRRT group. The perioperative conditions and postoperative complications of the two groups were compared along with the prognoses of the groups to analyze the high-risk factors of the postoperative CRRT.Results189 (36.91%) patients developed AKI within 1 year after the liver transplantation surgery. There were 18 patients in the CRRT group and 171 in the non-CRRT group. The differences in the preoperative conditions were not statistically significant between the two groups. Compared with the non-CRRT group, patients in the CRRT group had significantly longer transplantation times, higher volumes of intraoperative hemorrhage, and increased incidence of postoperative unscheduled surgery, postoperative primary nonfunction of the transplanted liver, secondary liver transplantation, hepatic artery occlusion, and intestinal fistula (P < 0.05). Moreover, the proportion of patients in AKI stage 3 is higher in the CRRT group (83.33%) than that in the non-CRRT group (11.11%), P < 0.001. The median time to initiate CRRT was 10 days postoperatively, the median number of CRRT treatments per patient was 2 times, the average duration of each CRRT treatment was 10.1 h, and the average rate of the decrease in blood creatinine per treatment was 25.6%. Results of multivariate logistic regression analysis showed that AKI stage 3 [OR=40.000, 95%CI (10.598, 150.969), P = 0.016], postoperative unscheduled surgery [OR=6.269, 95%CI (3.051, 26.379), P = 0.007], and hepatic artery occlusion [OR = 17.682, 95%CI (1.707, 40.843), P = 0.001] were recognized as risk factors for postoperative AKI with CRRT therapy. The one- and two-year survival rates were 72.22% and 72.22% in the CRRT group, respectively; and 97.08% and 96.49% in the non-CRRT group, accordingly. There were statistically significant differences in the one- and two-year survival rates between the two groups (P < 0.001).ConclusionThe incidence of AKI after liver transplantation in pediatric patients was high. Patients with AKI stage 3, hepatic artery occlusion, and underwent unscheduled surgery postoperatively were with a high likelihood of receiving CRRT, which was related to a lower one- and two-year survival rates. CRRT effectively improved the one- and two-year survival rates.

Liver transplantation of partial grafts after ex situ splitting during hypothermic oxygenated perfusion-The HOPE-Split pilot study.

Partial liver grafts from ex situ splitting are considered marginal due to prolonged static cold storage. The use of ex situ hypothermic oxygenated perfusion (HOPE) may offer a strategy to improve preservation of ex situ split grafts. In this single-center pilot study, we prospectively performed ex situ liver splitting during HOPE (HOPE-Split) for adult and pediatric partial grafts over a 1-year period (November 1, 2020 to December 1, 2021). The primary safety endpoint was based on the number of liver graft-related adverse events (LGRAEs) per recipient, including primary nonfunction, biliary complications, hepatic vascular complications, and early relaparotomies and was compared with consecutive single-center standard ex situ split transplantations (Static-Split) performed from 2018 to 2020. Secondary endpoints included preservation characteristics and early outcomes. Sixteen consecutive HOPE-Split liver transplantations (8 HOPE-Split procedures) were included and compared with 24 Static-Splits. All HOPE-Split grafts were successfully transplanted, and no graft loss nor recipient death was encountered during the median follow-up of 7.5 months (interquartile range, 5.5-12.5). Mean LGRAE per recipient was similar in both groups (0.31 ± 0.60 vs. 0.46 ± 0.83; p=0.78) and split duration was not significantly increased for HOPE-Split (216 vs. 180 min; p=0.45). HOPE-Split grafts underwent perfusion for a median of 125 min, which significantly shortened static cold storage (472 vs. 544 min; p=0.001), whereas it prolonged total ex vivo preservation (595 vs. 544 min; p=0.007) and reduced neutrophil infiltration on reperfusion biopsies (p=0.04) compared with Static-Split. This clinical pilot study presents first feasibility and safety data for transplantation of partial liver grafts undergoing ex situ split during HOPE and suggests improved preservation compared with static ex situ splitting. These preliminary results will allow to set up large-scale trials on the use of machine perfusion in pediatric and split-liver transplantation.

Kidney Transplantation After Rescue Allocation-the Eurotransplant Experience: A Retrospective Multicenter Outcome Analysis.

At Eurotransplant (ET), kidneys are transferred to "rescue allocation" (RA), whenever the standard allocation (SA) algorithms Eurotransplant Kidney Allocation System (ETKAS) and Eurotransplant Senior Program (ESP) fail. We analyzed the outcome of RA. Retrospective patient clinical and demographic characteristics association analyses were performed with graft outcomes for 2422 recipients of a deceased donor renal transplantation (DDRT) after RA versus 25 481 after SA from 71 centers across all ET countries from 2006 to 2018. Numbers of DDRTs after RA increased over the time, especially in Germany. RA played a minor role in ESP versus ETKAS (2.7% versus 10.4%). RA recipients and donors were older compared with SA recipients and donors, cold ischemia times were longer, waiting times were shorter, and the incidence of primary nonfunction was comparable. Among ETKAS recipients, HLA matching was more favorable in SA (mean 3.7 versus 2.5). In multivariate modeling, the incidence of graft loss in ETKAS recipients was reduced in RA compared with SA (subdistribution hazard ratio, 0.80; 95% confidence interval [0.70-0.91], P < 0.001), whereas other outcomes (mortality, death with functioning graft (DwFG)) were not significantly different. None of the 3 outcomes were significantly different when comparing RA with SA within the ESP program. Facing increased waiting times and mortality on dialysis due to donor shortage, this study reveals encouragingly positive DDRT outcomes following RA. This supports the extension of RA to more patients and as an alternative tool to enable transplantation in patients in countries with prohibitively long waiting times or at risk of deterioration.

Novel benchmark values for redo liver transplantation – does the outcome justify the effort?

Abstract 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 &amp;lt;=25, absence of portal vein thrombosis, no mechanical ventilation before surgery, receiving a graft from a donor after brain death. In addition, early reLT including those for primary non-function (PNF) were excluded. Clinically relevant endpoints covering intra- and postoperative course were selected and complications were graded by severity using the Clavien-Dindo classification and the comprehensive complication index (CCI). The benchmark cutoff for each outcome was derived from the 75th percentile of the median values of all benchmark centers, indicating the “best achievable” result. To assess the utility of the newly established benchmark values, we analyzed patients who received reLT for PNF (non-benchmark patients). Results Out of 1110 reLT 413 (37.2%) qualified as benchmark cases. Benchmark values included: Length of intensive care unit and hospital stay: &amp;lt;=6 and &amp;lt;=24 days, respectively; Clavien-Dindo grade &amp;gt;=3a complications and the CCI at 1 year: &amp;lt;=76% and &amp;lt;=72.2, respectively; in-hospital and 1-year mortality rates: &amp;lt;=14.0% and &amp;lt;=14.3%, respectively. The cutoffs for transplant-specific complications such as biliary complications at 1 year, outflow problems at 1 year and hepatic artery thrombosis at discharge were &amp;lt;=27.3%, &amp;lt;=2.5% and &amp;lt;=4.8%, respectively. Patients receiving a reLT for PNF showed mean outcome values all outside the reLT benchmark values. In-hospital mortality rate was 34.4% and the mean CCI at discharge 68.8. 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.

Outcomes Following Extrahepatic and Intraportal Pancreatic Islet Transplantation: A Comparative Cohort Study.

Preliminary studies show promise for extrahepatic islet transplantation (ITx). However, clinical comparisons with intraportal ITx outcomes remain limited. This single-center cohort study evaluates patients receiving extrahepatic or intraportal ITx between 1999 and 2018. Primary outcome was stimulated C-peptide level. Secondary outcomes were fasting plasma glucose, BETA-2 scores, and fasting C-peptide level. Multivariable logistic modeling evaluated factors independently associated with a composite variable of early graft failure and primary nonfunction within 60 d of ITx. Of 264 patients, 9 (3.5%) received extrahepatic ITx (gastric submucosal = 2, subcutaneous = 3, omental = 4). Group demographics were similar at baseline (age, body mass index, diabetes duration, and glycemic control). At 1-3 mo post-first infusion, patients receiving extrahepatic ITx had significantly lower stimulated C-peptide (0.05 nmol/L versus 1.2 nmol/L, P < 0.001), higher fasting plasma glucose (9.3 mmol/L versus 7.3 mmol/L, P < 0.001), and lower BETA-2 scores (0 versus 11.6, P < 0.001) and SUITO indices (1.5 versus 39.6, P < 0.001) compared with those receiving intraportal ITx. Subjects receiving extrahepatic grafts failed to produce median C-peptide ≥0.2 nmol/L within the first 60 d after transplant. Subsequent intraportal infusion following extrahepatic transplants achieved equivalent outcomes compared with patients receiving intraportal transplant alone. Extrahepatic ITx was independently associated with early graft failure/primary non-function (odds ratio 1.709, confidence interval 73.8-39 616.0, P < 0.001), whereas no other factors were independently predictive. Using current techniques, intraportal islet infusion remains the gold standard for clinical ITx, with superior engraftment, graft function, and glycemic outcomes compared with extrahepatic transplantation of human islets.

Good post-transplant outcomes using liver donors after circulatory death when applying strict selection criteria: a propensity-score matched-cohort study

Introduction and ObjectivesOutcomes of liver transplantation (LT) with donors after circulatory death (DCD) have been considered suboptimal due to higher rates of ischemic cholangiopathy, especially when the super-rapid recovery (SRR) technique is used. This study aimed to compare the incidence of complications between recipients receiving DCD vs those receiving donors after brain death (DBD) in a large-volume liver transplant centre. MethodsWe performed a retrospective cohort study (LT from January 2015 to December 2018) comparing recipients who underwent a LT with DCD vs. a control group of LT with DBD, matched 1:1 without replacement by propensity score matching that included the following variables: LT indication, recipient sex and age, donor age and MELD score. Results51 recipients with DCD-LT (29 SRR, 22 normothermic regional perfusion [NRP]) were matched with 51 DBD-LT recipients. Biliary complications were more frequent in DCD, 10% (n=5), all with SRR technique, vs 2% (n=1) in the DBD group, p=0.2. Two patients (4%) suffered primary graft non-function in the DCD group (1 SRR and 1 NRP) versus zero in the DBD group (p=0.49). Postoperative bleeding and reinterventions were also higher in the DCD group: 7 (13.7%) vs 1 (1.95%) and 8 (15.7%) vs 2 (3.9%) respectively (p=0.06 and 0.09). On the 1st postoperative day AST/ALT peak was higher in DCD (p≤0001). The incidence of rejection, vascular complications, renal injury, hospital stay, and readmissions were similar in both groups. Cumulative 1-, 2-, 3- and 4-year graft and patient survival were also similar. ConclusionsDCD donors are an adequate option to increase the donor pool in LT, achieving similar graft and patient survival rates to those achieved with DBD donors, especially when the NRP technique is used.

Simultaneous nephrectomy during kidney transplantation for polycystic kidney disease does not detrimentally impact comorbidity and graft survival.

BACKGROUNDThe lack of space, as an indication for a native unilateral nephrectomy for positioning a future kidney graft in the absence of other autosomal dominant polycystic kidney disease-related symptoms, remains controversial.AIMTo evaluate the surgical comorbidity and the impact on graft survival of an associated ipsilateral native nephrectomy during isolated kidney transplantation in patients with autosomal dominant polycystic kidney disease. METHODSOne hundred and fifty-four kidney transplantations performed between January 2007 and January 2019 of which 77 without (kidney transplant alone (KTA) group) and 77 with associated ipsilateral nephrectomy (KTIN group), were retrospectively reviewed. Demographics and surgical variables were analyzed and their respective impact on surgical comorbidity and graft survival. RESULTSCreation of space for future graft positioning was the main reason (n = 74, 96.1%) for associated ipsilateral nephrectomy. No significant difference in surgical comorbidity (lymphocele, wound infection, incisional hernia, wound hematoma, urinary infection, need for blood transfusion, hospitalization stay, Dindo Clavien classification and readmission rate) was observed between the two study groups. The incidence of primary nonfunction and delayed graft function was comparable in both groups [0% and 2.6% (P = 0.497) and 9.1% and 16.9% (P = 0.230), respectively, in the KTA and KTIN group]. The 1- and 5-year graft survival were 94.8% and 90.3%, and 100% and 93.8%, respectively, in the KTA and KTIN group (P = 0.774). The 1- and 5-year patient survival were 96.1% and 92.9%, and 100% and 100%, respectively, in the KTA and KTIN group (P = 0.168). CONCLUSIONSimultaneous ipsilateral native nephrectomy to create space for graft positioning during kidney transplantation in patients with autosomal dominant polycystic kidney disease does not negatively impact surgical comorbidity and short- and long-term graft survival.

Machine perfusion in liver transplantation

Although liver transplantation is a true success story, many patients still die awaiting an organ. The increasing need for liver grafts therefore remains an unsolved challenge to the transplant community. To address this, transplant donor criteria have been expanded and, for example, more liver grafts with significant steatosis or from donors with circulatory death are being used. These marginal grafts, however, carry an increased risk of graft-associated complications, such as primary nonfunction, delayed graft function, or late biliary injuries. Therefore, reliable assessment of graft viability before use is essential for further success. To achieve this, machine liver perfusion, a procedure developed more than 50 years ago but almost forgotten at the end of the last century, is again of great interest. We describe in this review the clinical most applied machine perfusion techniques, their mechanistic background, and a novel concept of combining immediate organ assessment during hypothermic oxygenated perfusion, followed by an extended phase of normothermic machine perfusion, with simultaneous ex situ treatment of the perfused liver. Such a new approach may allow the pool of usable livers to dramatically increase and improve outcomes for recipients.