Safety and Efficacy of Everolimus Rescue Treatment After Pediatric Living Donor Liver Transplantation

Ueno T., Kodama T., Noguchi Y., et al. Safety and Efficacy of Everolimus Rescue Treatment After Pediatric Living Donor Liver Transplantation. Transplantation Proceedings 52, 1829 (2020); https://doi.org/10.1016/j.transproceed.2020.01.159.
Purpose: Everolimus (EVR) is a derivative of sirolimus with a similar mechanism of action. The safety and efficacy of EVR after pediatric living donor liver transplantation (LDLT) are currently unknown. The purpose of this study was to examine the safety and efficacy of EVR as rescue therapy after pediatric LDLT. Methods: This study included patients younger than 19 years of age who received EVR after LDLT at our institution. EVR was administered as rescue treatment in addition to tacrolimus. In 21 patients, EVR dose, trough level, outcomes, and adverse effects were assessed. Results: Original diseases of patients consisted of biliary atresia (n = 11), Alagille syndrome (n = 3), fulminant hepatitis (n = 3), hepatoblastoma (n = 2), and other (n = 2). Mean age at transplant was 2.0 years (range 0.6-6.2 years). Mean age at initial EVR administration was 8.0 years (range 0.9-18.9 years). Indications for EVR use were graft fibrosis (n = 8), refractory acute cellular rejection (n = 5), renal sparing (n = 4), hepatoblastoma (n = 2), and chronic rejection (CR) (n = 2). Mean duration of administration was 17.1 months (range 2.1-60.4 months). Mean dose was 0.5 mg/m2 twice daily. Mean EVR trough level was 2.5 ng/mL (range 1.5-5.0 ng/mL). Liver function improved and fibrosis did not progress in all patients with CR. However, 14 patients (67%) experienced adverse effects that required EVR dose reduction or discontinuation. Conclusion: EVR is tolerable for pediatric patients after LDLT with dose adjustment. EVR had a certain effect to relieve progression on CR. Further follow-up is required.