Research agenda for pediatric gastroenterology, hepatology and nutrition: transplantation. Report of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition for the Children's Digestive Health and Nutrition Foundation.

Persistent detection of Epstein-Barr virus DNA after pediatric liver transplantation: Unclear risks and uncertain responses

Lymphoproliferative disorders after liver transplantation

Immunosuppression in Pediatric Liver and Intestinal Transplantation: A Closer Look at the Arsenal

Underimmunization of the solid organ transplant population: An urgent problem with potential digital health solutions.

Herpes Simplex Virus (HSV)-1 and -2, and Varicella Zoster Virus (VZV)

Tacrolimus, a calcineurin inhibitor, is the maintenance immunosuppression of choice in paediatric liver transplant (LT) recipients.1–3 However, in selective cases, when this therapy requires discontinuation, sirolimus, a mTOR inhibitor is...

Multisystem inflammatory syndrome in children associated with SARS-CoV-2 in a solid organ transplant recipient.

Angiotensin II type-1 receptor antibody (AT1R-Ab) has been associated with vascular injury and kidney dysfunction in pediatric kidney transplant recipients. The role of AT1R-Ab in the development of chronic kidney disease in pediatric liver and intestinal transplant recipients has not been explored. Twenty-five pediatric intestinal transplant recipients and 79 pediatric liver transplant recipients had AT1R-Ab levels measured at varying time points in the post-transplant period. Estimated glomerular filtration rate (eGFR) was determined using creatinine based CKiD U25 equation and measured at time of AT1R-Ab measurement, at 1year post-AT1R-Ab measurement, at 5years post-AT1R-Ab measurement, and at the most recent routine clinic visit. The prevalence of hypertension and antihypertensive medication use were also evaluated. Younger age at time of AT1R-Ab measurement was associated with AT1R-Ab positivity in liver transplant recipients. There was no association between AT1R-Ab status and change in eGFR, prevalence of hypertension, or use of antihypertensive medications at the described time points. AT1R-Ab positivity was not associated with a decline in eGFR or hypertension in pediatric liver and intestinal transplant recipients. Further studies are needed using other markers of kidney function, such as cystatin C, to validate this finding. A higher resolution version of the Graphical abstract is available as Supplementary information.

BackgroundTransition to adult care can trigger certain problems for pediatric liver transplant recipients. At our institution, the same transplant team performs both adult and pediatric liver transplantation and post-transplant care; thus, pediatric liver transplant recipients do not have to be transferred. However, it is unclear whether this system affects the recipient’s outcome during the transition period. Therefore, we retrospectively assessed pediatric liver transplant recipients who reached adulthood at our institution.Material/MethodsThis was a single-center, retrospective study involving consecutive pediatric living-donor liver transplant recipients who reached the age of 18 by October 2017. A total of 36 recipients, 20 females and 16 males, were included in the study.ResultsThe 5- and 10-year patient survival after reaching the age of 18 was 100% and 93%, respectively. All of the 3 patients who died had been suffering from secondary biliary cirrhosis due to biliary stricture. In 5 patients (13.9%), biliary stricture became symptomatic or recurred after reaching the age of 18 years. Late-onset acute rejection and chronic rejection developed in 2 (5.6%) and 4 patients (11.1%), respectively. Only 4 (11.1%) patients were obviously noncompliant. We found no significant association between compliance and rejection or survival. Among the patients who are 18 years old and older, 5 (13.9%) had a psychiatric diagnosis.ConclusionsPediatric liver transplant recipients who underwent transplant surgery and received post-transplant care at our institution have good long-term outcomes. This suggests that having the same team perform both adult and pediatric transplantation and post-transplant care is beneficial for young adult recipients.

To determine the rate of occurrence and genotypes of Epstein-Barr Virus (EBV) among pediatric renal and liver transplants recipients. Observational study. Vision Research Foundation referral center and Institute of Liver Disease and Transplantation, Chennai, India. 70 pediatric solid organ transplant recipients and 60 voluntary healthy donors. Polymerase chain reaction (PCR) for detection and genotyping of EBV were carried out using genes targeting Viral capsid antigen, Nuclear antigen 1, 2 and 3, followed by real time PCR for viral load determination and further confirmed by phylogenetic analysis. EBV was detected in 35 (51.4%) samples (32 liver and 4 renal transplants) with high viral load. Type A was detected in 33 samples, Type B in 2 liver transplant patients, and co-infection in one liver transplant patient who developed Post-transplant Lymphoproliferative Disorder (PTLD). Real time PCR results correlated with conventional PCR. The mean viral load for patients who did not develop PTLD was 50,424 copies/mL. Overall EBV load in patient with PTLD ranged from 1,40,392 copies/mL prior to PTLD diagnosis to 62,124 copies /mL post treatment. EBV infection is the high risk factor for PTLD after liver transplantation. PCR targeting of EBV can be applied to diagnose EBV infections and monitor treatment for EBV in pediatric solid organ transplant recipients.

To describe and compare the results of delirium screening in the immediate post-transplant PICU admission for pediatric intestinal, liver, and renal transplant recipients. We also examined associations with known and suspected risk factors for pediatric delirium (PD). Retrospective analysis of a single-center cohort, 2016-2022. Twenty-four-bed PICU in a high-volume transplant center. All intestinal, liver, and renal transplant recipients under 23 years old admitted between July 2016 and August 2022. We identified 211 pediatric transplant recipients: intestinal ( n = 36), liver ( n = 78), and renal ( n = 97). Results of the Cornell Assessment for PD during the immediate post-transplant PICU admission were reviewed and patients were categorized into screen positive, screen negative, and unscreened. Corresponding data on known and suspected risk factors for PD were also collected. Data on delirium subtypes were not collected. Screens were available for 156 of 211 patients (74%) who were included in the final analysis. The prevalence of a positive screen by transplant category was: intestine 80% (24/30), liver 75% (47/63), and renal 14% (9/63). A positive screen was associated with younger age, greater duration of mechanical ventilation, and greater PICU length of stay (LOS) in bivariate analysis. In multivariable analysis, age and PICU LOS remained strongly correlated with a positive screen ( p < 0.05). Deep sedation and agitation as categorized by the State Behavioral Scale was associated with a positive screen, as was significant iatrogenic withdrawal symptoms ( p < 0.05). Most patients screened positive by post-transplant days 2 and 3 (58/80 [72%] and 64/80 [80%], respectively). In our 2016 to 2022 experience, we found a high prevalence of positive PD screens in pediatric intestinal and liver transplant recipients in the immediate post-transplant PICU admission. A positive screen was associated with younger age and greater PICU LOS.

Not everything that counts can be counted: Tracking long-term outcomes in pediatric liver transplant recipients

ABSTRACTMethicillin-resistant Staphylococcus aureus infections are a significant cause of morbidity and mortality in pediatric liver transplant (LT) recipients. Physiological changes following LT may affect vancomycin pharmacokinetics; however, appropriate dosing to achieve sufficient drug exposure (i.e., 24-h area under the concentration-time curve [AUC24]/MIC ≥ 400) in pediatric LT recipients has not been reported. This retrospective pharmacokinetics study of LT recipients aged <18 years utilized data on patient characteristics with vancomycin concentrations and dosing information obtained from electronic medical records. Population pharmacokinetics analysis was conducted by nonlinear mixed-effects modeling with the Phoenix NLME software. Potential covariates were screened with univariate and multivariate analysis. Monte Carlo simulations were performed using the final model to explore appropriate dosing. The study included 270 pharmacokinetics profiles encompassing 1,158 concentrations measured in 161 patients. The median age was 13.3 (interquartile range, 7.6 to 53.5) months, serum creatinine (sCr) was 0.16 (0.12 to 0.23) mg/dl, and days from LT (DFLT) was 17 (6 to 31). Multivariate analysis demonstrated that lower sCr and shorter DFLT were associated with higher clearance. By post hoc estimation, the average clearance and volume of distribution were 0.18 liters/h/kg and 1.01 liters/kg, respectively. The Monte Carlo simulations revealed that only 16% of patients achieved an AUC24/MIC of ≥400 with the assumed vancomycin MIC of 1 μg/ml. DFLT and sCr were significant covariates for vancomycin clearance in pediatric LT recipients. Standard vancomycin dosing may be insufficient, and higher or more frequent dosing may be required to achieve an AUC24/MIC of ≥400 in pediatric LT recipients with normal renal function.IMPORTANCE We evaluated vancomycin pharmacokinetics in pediatric LT recipients and developed a population pharmacokinetics model by considering various factors that might account for alterations in vancomycin pharmacokinetics. Our analyses revealed that lower serum creatinine levels and a shorter duration from the day of LT were associated with higher vancomycin clearance and led to subtherapeutic drug exposure. We also performed Monte Carlo simulations to determine the appropriate dosing strategy in pediatric LT recipients, which revealed that a standard vancomycin dosing might be insufficient and that higher or more frequent dosing might be necessary to achieve an AUC24/MIC of ≥400 in pediatric LT recipients with normal renal function. To the best of our knowledge, this is the first study to assess vancomycin pharmacokinetics in pediatric LT recipients by population pharmacokinetics analysis.

After completing this article, readers should be able to: 1. Compare the results of pediatric heart transplantation with those of transplantation in adults, including the survival rates. 2. Compare and contrast the indications for pediatric heart transplant among those younger and older than 1 year of age. 3. List the common complications after pediatric heart transplantation. 4. Compare and contrast new immunosuppressive agents (tacrolimus, mycophenolate, humanized anti-Tac antibodies) and standard therapies (cyclosporine, azathioprine, prednisone, antithymocyte globulin). 5. Describe the controversy surrounding the proper management of infants who have hypoplastic left heart syndrome. Not long after the first successful human heart transplant was performed, the first neonatal heart transplant was attempted. In December of 1967, Kantrowitz and colleagues at Maimonides Hospital in New York transplanted the heart of an anencephalic infant into a 3-week-old who had tricuspid atresia. Although the recipient survived only 6.5 hours, the technical feasibility of cardiac transplantation in the pediatric patients was proven. Thirty-three years later, heart transplantation has gained widespread acceptance as a standard treatment modality for end-stage cardiomyopathy or noncorrectable congenital heart disease in infants and children. The 2 years following Barnard’s pioneering first transplant saw explosive growth in the field of adult heart transplantation, but poor 1-year survival dampened much of the initial enthusiasm and with it, any hope for bringing heart transplantation to the pediatric population. Most centers eventually abandoned the procedure, and many physicians denounced the concept. However, a few centers persisted, most notably Dr Norman Shumway and colleagues at Stanford, gradually improving survival through strong collaborations with basic immunologists and cardiac pathologists. By the mid-1970s, heart transplantation had been extended successfully to teenagers. The introduction of the “wonder drug” cyclosporine in 1980 so dramatically improved survival in adult cardiac transplant recipients that the extension of transplantation to even younger patients became feasible. Almost as important as …

Objective: to investigate the association between plasma TGF-β1 levels in pediatric liver transplant (LT) recipients, both preand post-transplantation, and the polymorphic alleles and haplotypes at rs1800469 and rs1800470 loci of the TGFB1 gene.Materials and methods. The study cohort comprised 135 pediatric LT recipients, aged 3 to 98.4 months (mean age 8.2 years, median 8 months). The control group consisted of 77 healthy individuals, aged 30.3 ± 5.2 years. Plasma TGF-β1 levels were quantified using ELISA. Genomic DNA from participants was analyzed for the polymorphic loci rs1800469 and rs1800470 of the TGFB1 gene using real-time polymerase chain reaction PCR with TaqMan probes.Results. Blood TGF-β1 level in pediatric LT recipients pre-transplant was 4.6 (1.1–9.5) ng/mL. One month post-transplant, cytokine level increased to 6.3 (1.7–15.0) ng/mL (p = 0.008), and after one year, it rose further to 7.0 (1.9–13.5) ng/mL (p = 0.0001). Healthy adults had significantly higher TGF-β1 levels, with a median of 11.7 (6.4–16.9) ng/mL (p = 0.0000), compared to pediatric recipients. The distribution frequencies of the rs1800469 and rs1800470 polymorphic alleles in pediatric LT recipients did not significantly differ from those in healthy individuals. However, the occurrence of rare haplotypes (T-T and C-C) was significantly higher in pediatric recipients. Before transplantation and 1 month after the procedure, TGF-β1 levels in pediatric recipients were not associated with the carriage of the studied alleles or haplotypes. However, at 1-year post-transplant, higher TGF-β1 levels in pediatric recipients were significantly associated with the major alleles (C/C + C/T) of rs1800469 and the rs1800470 T/T genotype, as well as with the T-T haplotype. In healthy individuals, TGF-β1 levels were not influenced by the rs1800469 and rs1800470 alleles individually, but high cytokine levels were associated with the C-C haplotype.Conclusion. In pediatric LT recipients, elevated TGF-β1 levels at 1-year post-transplant are associated with the presence of the major alleles C (rs1800469) and T (rs1800470), as well as the T-T haplotype of the TGFB1 gene. This suggests that these polymorphic loci may influence the development of post-transplant complications and could potentially serve as biomarkers for predicting clinical outcomes in LT.