Immunosuppression in pediatric liver transplant recipients: Unique aspects

Miloh, Tamir; Barton, Andrea; Wheeler, John F.; Pham, Yen; Hewitt, Winston R.; Keegan, Tara; Sanchez, Christine; Bulut, Pinar; Goss, John A.

doi:10.1002/lt.24677

Cited by 79 publications

(86 citation statements)

References 75 publications

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“…In spite of the fact that neonatal (group 1) and infant (group 2) grafts seemed to have higher rate of SFSS, the recipients in these two groups showed favorable outcome in acute rejection, and the recipients in group 3 exhibited significantly higher rate of acute rejection compared with the combination of groups 1 and 2 in our study. It has long been claimed that immune tolerance is more likely to be induced in children due to the immatureness of immune system . The immunosuppressive protocol in our center for recipient younger than 6 years old is the combination of tacrolimus and steroids, unlike adult recipients, MMF is not considered unless in recipients who received ABO incompatible donors or had high risk of postoperative immune rejection.…”

Section: Discussionmentioning

confidence: 99%

Utility of neonatal donors in pediatric liver transplantation: A single‐center experience

Gao

Song

et al. 2019

Pediatric Transplantation

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Background The lack of age‐ and size‐matched organs result in higher waiting list mortality in pediatric recipients than adults. Organs from deceased newborns and infants are a valuable source to increase donor pool in pediatric liver transplantation. However, the feasibility and safety of using neonatal donors have not been well evaluated. Methods From 2014 to 2016, 48 deceased donor pediatric liver transplantations with donor age younger than 1 year old in our center were enrolled in this study. The recipients were divided into three groups based on the donor age (<1 month, 1 month ≤ to <3 months, and 3 months ≤ to <1 year). Recipient's characteristics, perioperative data, and postoperative complications were compared. Results Two‐year patient survival rates were 87.5%, 94.4%, and 95.5%, and 2‐year graft survival rates were 75%, 94.4%, and 95.5%, respectively, without significant difference. The liver grafts from donors younger than 3 months were more advantageous in terms of acute rejection and virus infection, while the young grafts were related to slight higher incidence of hepatic artery thrombosis and SFSS. Those complications could be effectively prevented or treated by our perioperative care strategies. In addition, eight recipients who received neonatal livers achieved comparable outcomes with recipients with older livers. Conclusion Our data revealed that the application of liver grafts from donors younger than 1 year old could achieve excellent outcome. In particular, neonatal donors could be safely used in well‐selected patients.

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Section: Discussionmentioning

confidence: 99%

Utility of neonatal donors in pediatric liver transplantation: A single‐center experience

Gao

Song

et al. 2019

Pediatric Transplantation

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“…The incidence of neurotoxicity is reported to be higher in patients who receive tacrolimus . The expression of cytochrome P450 (CYP) 3A7 at birth declines during the first 6 months of life because of the presence of unstable CYP450 polymorphisms in children, together with individual variability, whereas CYP3A4 reaches adult levels after 1 year of age . Moreover, serial intraindividual and interindividual variabilities of CYP3A activity have been reported .…”

Section: Discussionmentioning

confidence: 99%

Living donor liver transplantation during the first 3 months of life

et al. 2017

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Living donor liver transplantation (LDLT) is now an established technique for treating children with end-stage liver disease. Few data exist about liver transplantation (LT) for exclusively young infants, especially infants of <3 months of age. We report our single-center experience with 12 patients in which LDLT was performed during the first 3 months of life and compare the results with those of older infants who underwent LT. All of the patients were treated at the National Center of Child Health and Development, Tokyo, Japan. Between November 2005 to November 2016, 436 children underwent LT. Twelve of these patients underwent LT in the first 3 months of life (median age, 41 days; median weight, 4.0 kg). The indications for transplantation were fulminant hepatic failure (n = 11) and metabolic liver disease (n = 1). All the patients received the left lateral segment (LLS) in situ to mitigate the problem of graft-to-recipient size discrepancy. A reduced LLS graft was used in 11 patients and a segment 2 monosegment graft was used in 1 patient. We compared the results with those of infants who were 4-6 months of age (n = 67) and 7-12 months of age (n = 110) who were treated in the same study period. There were significant differences in the Pediatric End-Stage Liver Disease score and the conversion rate of tacrolimus to cyclosporine in younger infants. Furthermore, the incidence of biliary complications, bloodstream infection, and cytomegalovirus infection tended to be higher, whereas the incidence of acute cellular rejection tended to be lower in younger infants. The overall cumulative 10-year patient and graft survival rates in recipients of <3 months of age were both 90.9%. LDLT during the first 3 months of life appears to be a feasible option with excellent patient and graft survival. Liver Transplantation 23 1051-1057 2017 AASLD.

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“…The management of immunosuppression in pediatric liver transplant is complex and usually includes use of calcineurin inhibitors . Tacrolimus has become the cornerstone in immunosuppression of pediatric liver transplant patients.…”

Section: Introductionmentioning

confidence: 99%

“…Tacrolimus has become the cornerstone in immunosuppression of pediatric liver transplant patients. Tacrolimus therapeutic drug monitoring is performed in the post‐transplant routine based on the narrow therapeutic window, high variability in tacrolimus pharmacokinetics, and the previously documented relationship between systemic exposure and AEs to this calcineurin inhibitor …”

Section: Introductionmentioning

confidence: 99%

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Pharmacoepidemiology of tacrolimus in pediatric liver transplantation

Riva

Schaiquevich

Guido

et al. 2017

Pediatric Transplantation

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AEs during immunosuppressive treatment with tacrolimus are very common. We retrospectively evaluated FK safety and efficacy in a large pediatric liver transplant cohort in Latin America. During 2-year follow-up, we analyzed data from patients who underwent liver transplantation over the period 2010-2012 and recorded FK exposure, AEs, and AR episodes. AEs were classified according causality and severity. Tacrolimus exposure before and during AE was compared using Wilcoxon matched-pairs test. Kaplan-Meier curves were used for survival analysis. In total, 46 patients (out of 72 patients) experienced 69 AEs, such as hypomagnesemia (49%), PTLD (6%), hypertension (6%), and/or nephrotoxicity (22%). 43% of AEs were classified as moderate or serious, and 89% were assigned as probable or definitive. Patients who had one or more AR episodes accounted for 65%. The 12-month acute rejection-free survival was 41% (95% CI, 30.1%-53.1%). A significant difference was observed in FK trough concentrations before and during hypomagnesemia and nephrotoxicity (P<.05). This study is the first report of FK safety in a large group of pediatric liver transplant patients in Latin America. Children experience AEs, even in protocols with low FK doses. Therapeutic monitoring is an important tool to manage immunosuppressive schemes containing tacrolimus in vulnerable populations.

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Immunosuppression in pediatric liver transplant recipients: Unique aspects

Cited by 79 publications

References 75 publications

Utility of neonatal donors in pediatric liver transplantation: A single‐center experience

Utility of neonatal donors in pediatric liver transplantation: A single‐center experience

Living donor liver transplantation during the first 3 months of life

Pharmacoepidemiology of tacrolimus in pediatric liver transplantation

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