Search

Background: The role of protocol liver biopsies (PLB) in the follow-up of pediatric liver transplant recipients remains questionable. This single-center retrospective study aimed to evaluate their clinical impact on the long-term management of pediatric liver transplant recipients., Methods: We described histopathological lesions and clinical consequences for patient management of PLB performed 1, 5, 10, 15, 20, and 25 years after pediatric liver transplantation (LT)., Results: A total of 351 PLB performed on 133 patients between 1992 and 2021 were reviewed. PLB found signs of rejection in 21.7% of cases (76/351), and moderate to severe fibrosis in 26.5% of cases (93/351). Overall, 264 PLB (75.2%) did not cause any changes to patient care. Immunosuppression was enhanced after 63 PLB, including 23 cases of occult rejection. The 1-year PLB triggered significantly more changes, while biopsies at 15, 20, and 25 years produced the lowest rates of subsequent modifications. PLB had a significantly higher probability of inducing therapeutic changes if the patient had abnormal biological or imaging results (odds ratio [OR] 2.82 and 2.06), or a recent history of rejection or bacterial infection (OR 2.22 and 2.03)., Conclusion: Our results suggest that, although it often does not prompt any treatment changes, PLB could be performed because of its ability to detect silent rejection requiring an increase in immunosuppression. PLB could be carried out 1, 5, and 10 years after LT and then every 10 years in patients with normal biological and imaging results and no recent complications, while other patients could be kept on a 5-year protocol., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study was a Phase II, open-label, multicenter, single-arm, cross-over study comparing the pharmacokinetics (PK) of tacrolimus in stable pediatric kidney, liver, or heart allograft recipients converted from immediate-release tacrolimus (IR-T) to prolonged-release tacrolimus (PR-T). In Days -30 to -1 of screening period, patients received their IR-T-based regimen; during Days 1-7, patients received study IR-T (same dose as screening). On Day 7, the first 24-hours PK profile was taken; patients were then converted to PR-T (1 mg:1 mg), with a second 24-hours PK profile taken on Day 14. The primary end-point was tacrolimus area under the blood concentration-time curve over 24 hours (AUC 24 ); secondary end-points were maximum concentration C max and concentration at 24 hours C 24 . The predefined similarity interval for confidence intervals (CIs) of least squares mean (LSM) ratios was 80%-125%. The PK analysis set comprised 74 pediatric transplant recipients (kidney, n = 45; liver, n = 28; heart, n = 1). PR-T:IR-T LSM ratio (90% CI) was similar overall for AUC 24 , max , and C 24 , and for kidney and liver recipients for AUC 24 (LSM ratio, kidney 91.8%; liver 104.1%) and C 24 (kidney 90.5%; liver 89.9%). Linear relationship was similar between AUC 24 and C 24 , and between PR-T and IR-T (rho 0.89 and 0.84, respectively), suggesting that stable pediatric transplant recipients can be converted from IR-T to PR-T at the same total daily dose, using the same therapeutic drug monitoring method., (© 2019 The Authors. Pediatric Transplantation published by Wiley Periodicals, Inc.)

Cardiovascular diseases induce long-term morbidity and mortality of adult LT recipients. The aim of this retrospective study was to assess CVRF, lipid abnormalities, and atherosclerosis (appraised by c-IMT), more than 10 yr after pediatric LT. Thirty-one children who underwent LT between December 1990 and December 2000 were included. Median age at LT was 14 months (range 4-64), and median follow-up after LT was 11.9 yr (range 9.0-17.3). In our cohort, obesity (9.7%) and treated hypertension (9.7%) were rare. None of the patients was smoker or diabetic. High TC and TG were both observed in 6.5% of the patients. The mean c-IMT for male patients was 1.22 ± 1.55 and 1.58 ± 1.23 mm in female patients. Seven patients (22%) had a mean c-IMT above +2 s.d. Values below the 5th percentile were noted for LDL-cholesterol (58.1%), HDL-cholesterol (25.8%), apolipoprotein B (40%), and apolipoprotein A1 (20%). LDL-cholesterol and apolipoprotein B levels were significantly lower in patients treated by tacrolimus in comparison with CsA (p < 0.05). In conclusion, our results suggest that pediatric LT patients do not present significant CVRF; moreover, instead of hyperlipidemia, hypocholesterolemia (LDL-C) is frequent and immunosuppressive therapy is probably the cause., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Epstein-Barr virus (EBV) is known to establish latent infections in B-lymphocytes that can cause lymphoproliferative disorders particularly in immunocompromised patients. More recently, the development of rare EBV-associated smooth muscle tumors has been reported in transplant recipients. We herein describe 2 new cases of EBV-associated post-transplant smooth muscle tumors (EBV-PTSMT), including the first in a facial composite tissue graft recipient. Among the striking features shared by these 2 patients were their young ages, the fact that they were naïve for EBV before the transplantation, that they developed a post-transplant lymphoproliferative disorder before the diagnosis of EBV-PTSMT, and that they responded favorably to reduction of immunosuppression. Radiological and histologic features of EBV-PTSMT are shown. Finally, pathophysiology and therapeutic management of EBV-PTSMT are discussed based on a comprehensive review of the literature., (© 2013 John Wiley & Sons A/S.)

Uric acid may be involved in the development and progression of kidney diseases. Hyperuricemia is a common feature in adult liver transplant recipients but there is limited information in children. In order to estimate the incidence, predictors of hyperuricemia in pediatric liver transplant recipients, and to assess whether hyperuricemia may impact long-term renal function determined by measured GFR, we reviewed data of 70 children who received a first liver transplant between 1991 and 2005 (median follow-up 7.1 yr). Renal function tests performed annually included uric acid concentration, inulin and uric acid clearances. The cumulative incidence of hyperuricemia was 32% at 10-yr post-transplantation, mainly because of decreased urate excretion. The only factor significantly associated with an increased risk of hyperuricemia was older age. After adjustment for donor and recipient age, gender, primary liver disease, immunosuppression, and post-operative acute renal failure, hyperuricemia as time dependent variable tended to predict (p = 0.05) subsequent CRI. The control of serum urate concentration in eight of the 21 hyperuricemic patients either by nutritional management or by allopurinol was not followed by a significant GFR improvement. Hyperuricemia after liver transplantation in children is a frequent problem which needs further investigation.