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mTOR inhibitors in pediatric liver transplant recipients

Jérôme Dumortier1, Eduardo Couchonnal2, Florence Lacaille3

  • 1Department of digestive diseases, Edouard-Herriot hospital, hospices civils de Lyon, 69437 Lyon, France; University of Lyon, 69008 Lyon, France.

Clinics and Research in Hepatology and Gastroenterology
|December 12, 2018
PubMed

Insights

Mammalian target of rapamycin inhibitors (mTORi) are effective in pediatric liver transplant (LT) recipients for various indications. These mTOR inhibitors showed no significant impact on renal function and can help reduce calcineurin inhibitor toxicity.

Area of Science:

  • Pediatric Hepatology
  • Transplantation Immunology
  • Pharmacology

Background:

  • Mammalian target of rapamycin inhibitors (mTORi), including everolimus and sirolimus, have gained prominence in adult liver transplantation (LT).
  • Their application in pediatric LT recipients remains less characterized.
  • This study addresses the need to describe mTORi usage in pediatric LT cases.

Purpose of the Study:

  • To describe the clinical use of mTOR inhibitors (mTORi) in pediatric liver transplant (LT) recipients.
  • To analyze indications, efficacy, and adverse events associated with mTORi therapy in this population.

Main Methods:

  • Retrospective analysis of pediatric LT recipients who received mTORi before December 2017.
  • Data collected from 4 European pediatric LT centers.
  • Inclusion criteria focused on patients receiving mTORi, with analysis of demographics, indications, dosage, trough levels, adverse events, and outcomes.

Main Results:

  • Thirty pediatric LT recipients were analyzed, with a median age of 9.3 years at mTORi introduction.
  • Primary indications included liver malignancy (43.3%), calcineurin inhibitor (CNI) nephrotoxicity (26.7%), and rejection (23.4%).
  • After a median follow-up of 2.8 years, 50% experienced adverse events (hyperlipidemia, proteinuria, dermatitis, mucitis), and 23.3% discontinued mTORi. Importantly, mTORi introduction did not significantly impact renal function.

Conclusions:

  • mTOR inhibitors (mTORi) demonstrate utility in pediatric liver transplant (LT) recipients across diverse clinical scenarios.
  • They can serve to bolster immunosuppression or mitigate calcineurin inhibitor (CNI) toxicity.
  • The findings support the consideration of mTORi in managing pediatric LT patients, with careful monitoring for adverse events.
Abstract

Keywords:
liver transplantationmTOR inhibitoroutcomepediatric

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