Normothermic regional perfusion in controlled DCD liver procurement: Outcomes of the Swedish national implementation protocol.

Liver transplantation using donors after controlled circulatory death (cDCD) is associated with poorer graft survival and increased incidence of non-anastomotic biliary strictures (NAS) compared to livers procured from brain dead donors (DBD). The use of Normothermic regional perfusion (NRP) during cDCD procurement may improve post-transplant outcome and reduce the incidence of NAS. In Sweden cDCD liver transplantation was introduced through a national pilot protocol with mandatory NRP. This study aims to evaluate the outcome of cDCD liver transplantation during the pilot period. Donor and recipient data were collected on all cDCD liver transplants during the pilot period between 2020 - December 2022. Outcome on NAS, patient- and graft survival, early allograft dysfunction, acute kidney injury, and comprehensive complication index was compared to a matched cohort of 28 patients transplanted with a DBD liver between 2018-2022. 18 patients were transplanted with a liver from a cDCD donor after using NRP. Mean functional warm ischemia time was 29±6 minutes. Mean lactate reduction during NRP was 8.7±2.4 mmol/L, end NRP perfusate ALT was 1.4±1 µkat/L. When comparing cDCD liver transplant recipients to DBD, no significant differences were observed in the incidence of NAS, patient and graft survival, comprehensive complication index, early allograft dysfunction, nor acute kidney injury. Study protocol MRCP in cDCD patients showed no signs of subclinical biliary strictures. Evaluation of the Swedish national pilot of cDCD liver transplantation with mandatory NRP shows comparable outcomes to a matched DBD cohort with 94.4 one-year patient and graft survival and no incidence of NAS within the first year.

Potential of neonatal organ donation and outcome after transplantation.

Organ transplantation is limited by access to suitable organs. Infant recipient waitlist mortality is increased due to the scarcity of size-matched organs. Neonatal organ donors have been proposed as an underutilized source of donor organs. However, the literature on the actual prevalence and outcome of neonatal organ donation and transplantation is fragmented and not well analyzed. This literature review aims to summarize the available literature on the potential of neonatal organ donation and to analyze published cases of neonatal organ transplantation. A systematic search of the Medline and Cochrane databases yielded 2964 articles, which were screened for eligibility. In total, 86 articles were considered eligible, of which 34 were included in the literature review: 8 articles describing the potential of neonatal organ donation programs, and 26 articles describing clinical transplantation. Current evidence suggests there is a large pool of potential neonatal organ donors. In contrast, the literature on neonatal organ donor utilization is sparse. However, case series of successful kidney, heart, liver, hepatocyte, and multivisceral transplantation using organs from neonatal donors are summarized. Although good posttransplant organ function was achieved, the use of neonatal organs is associated with increased risk of thrombosis in both kidney and liver transplantation. Neonatal organ donation is a promising alternative for expanding the current donor pool. Experience is limited, but reported patient and graft survival are acceptable and more research on the subject is warranted.

Procurement and Evaluation of Hepatocytes for Transplantation From Neonatal Donors After Circulatory Death.

Hepatocyte transplantation is a promising treatment for liver failure and inborn metabolic liver diseases, but progress has been hampered by a scarcity of available organs. Here, hepatocytes isolated from livers procured for a neonatal hepatocyte donation program within a research setting were assessed for metabolic function and suitability for transplantation. Organ donation was considered for infants who died in neonatal intensive care in the Stockholm region during 2015-2021. Inclusion was assessed when a decision to discontinue life-sustaining treatment had been made and hepatectomy performed after declaration of death. Hepatocyte isolation was performed by three-step collagenase perfusion. Hepatocyte viability, yield, and function were assessed using fresh and cryopreserved cells. Engraftment and maturation of cryopreserved neonatal hepatocytes were assessed by transplantation into an immunodeficient mouse model and analysis of the gene expression of phase I, phase II, and liver-specific enzymes and proteins. Twelve livers were procured. Median warm ischemia time (WIT) was 190 [interquartile range (IQR): 80-210] minutes. Median viability was 86% (IQR: 71%-91%). Median yield was 6.9 (IQR: 3.4-12.8) x106 viable hepatocytes/g. Transplantation into immunodeficient mice resulted in good engraftment and maturation of hepatocyte-specific proteins and enzymes. A neonatal organ donation program including preterm born infants was found to be feasible. Hepatocytes isolated from neonatal donors had good viability, function, and engraftment despite prolonged WIT. Therefore, neonatal livers should be considered as a donor source for clinical hepatocyte transplantation, even in cases with extended WIT.

Comparison of cystatin C, creatinine, and iohexol clearance in pediatric liver transplantation-a retrospective cohort study.

Impaired renal function after pediatric (LT) is a recognized problem. Accurate monitoring of (GFR) is imperative to detect declining renal function. GFR can be estimated via s-creatinine and/or p-cystatin C or measured by inulin and or/iohexol clearances. We retrospectively compared eGFRcrea and eGFRcyst, to mGFRiohex after LT. Data from 91 children with 312 concomitant measurements of s-creatinine, p-cystatin C, and iohexol clearance, obtained between 2007 and 2015, were analyzed. eGFR was calculated by using the p-cystatin C-based CAPA and CKD-EPI formulas, and the s-creatinine-based Schwartz-LYON, FAS, revised Schwartz and MDRD formulas. Also, the arithmetic means of cystatin C-based and creatinine-based equations were used. Every calculated eGFR was compared to mGFRiohex in statistical correlation, accuracy, precision, bias, and misclassifications. Among the different equations, p-cystatin C-based formulas (CAPA and CKD-EPI) as well as the s-creatinine-based Schwartz-LYON formula showed the most correct estimates regarding accuracy (84-87.5%), bias (0.19-4.0 ml/min/1.73 m2 ), and misclassification rate (24.7-25%). In patients with renal function <75 ml/min/1.73 m2 , cystatin C-based formulas were significantly more accurate and less biased than creatinine-based formulas. In conclusion, S-creatinine could be used in a clinical setting on a regular basis in liver transplanted pediatric patients, with reliable results, if eGFR is calculated by the Schwartz-LYON formula. When suspected renal dysfunction, cystatin C-based eGFR should be calculated, since it gives more accurate and less biased estimates than creatinine-based eGFR, and should be confirmed by mGFR (iohexol).