The use of everolimus in pediatric liver transplant recipients: First experience in a single center

Abstract

The role of mTOR inhibitors, such as EVL, has not been established for pediatric liver transplant recipients up to now, although data from adult solid organ graft transplantation are very promising. Major complications following pediatric liver transplantation in the long-term course include chronic graft rejection and CNI-derived nephrotoxicity. The purpose of our study was to report first results using EVL as a rescue therapy in pediatric liver transplant recipients for the following indications: chronic graft dysfunction n=12, suspected CNI toxicity n=3, hepatoblastoma n=2, and recurrence of primary sclerosing cholangitis post-Ltx n=1. Four patients with chronic graft dysfunction developed completely normal liver function tests using EVL, six patients showed partial improvement, and two patients did not respond at all. One patient with CNI-induced nephropathy showed a slightly improved GFR. Both patients with hepatoblastoma did not develop any metastasis post-Ltx. First experience with EVL in pediatric liver transplant recipients shows promising results in patients with chronic graft failure when standard immunosuppression has failed. The future role of EVL in immunosuppressive protocols for children post-Ltx has to be proven by controlled clinical trials.

The role of everolimus in liver transplantation

“…An increase in GFR was noted in one of the three patients with suspected CNI nephrotoxicity, and patients with hepatoblastoma did not develop any metastasis. No new safety signals were observed 99. The ongoing H2305 study (NCT01598987) is the first prospective trial of everolimus (with reduced-exposure cyclosporine or tacrolimus) in pediatric liver transplant recipients.…”

Effectiveness of Sirolimus in Combination with Cyclosporine against Chronic Rejection in a Pediatric Liver Transplant Patient

“…However, the levels of AST and ALT tended to increase when sirolimus was added to the tacrolimus-based regimen. Recently, Nielsen et al 14) reported that 4 and 6 of 12 pediatric patients with chronic graft dysfunction after liver transplantation developed completely normal liver function and showed partial response, respectively. However, there was no precise analysis in drug interaction between tacrolimus and everolimus.…”

“…In the present study, both AST and ALT became well controlled after switching from tacrolimus to cyclosporine. Therefore, part of the patients with partial response of the past report 14) might develop completely normal liver function when tacrolimus was switched to cyclosporine. These results suggested that sirolimus in combination with cyclosporine might be an effective treatment against CR after liver transplantation.…”

Pädiatrische Lebertransplantation

“…Andere immunsuppressive Wirkstoffe, wie die Purinantagonisten Mykophenolatmofetil (MMF, Cellcept©) und Mykophenolsäure (Myfortic®) oder die mTORHemmer [Rapamycin (Sirolimus; Rapamune®), Everolimus (Certican®), mTOR: "mammalian target of rapamycin"] werden bisher bei pLTx nicht standardmäßig, sondern nur individuell v. a. F bei unerwünschten Wirkungen der Standardimmunsuppressiva -insbesondere einer kalzineurininhibitorassoziierten Nephrotoxizität -und F zur Intensivierung der Immunsuppression -dann in der Regel additiv zu einer Standardimmunsuppressioneingesetzt [51,56]. Diese beiden Wirkstoffgruppen weisen auch einen antiproliferativen Effekt auf, der insbesondere bei den mTORHemmern eine klinisch relevante Bedeutung haben könnte.…”