Everolimus is Safe as a Second-/Third-Line Therapy in Pediatric Autoimmune Hepatitis

Autoimmune hepatitis (AIH) can lead to progressive fibrosis in patients refractory to conventional therapy with prednisolone and azathioprine. The use of mammalian target of rapamycin (mTOR) inhibitors has recently emerged in refractory AIH, but no data have been published about everolimus in pediatric AIH to date. Our aim was to share our experience about everolimus as a second-/third-line therapy in pediatric AIH.

Pretransplant AIH patients aged 0-18 years who received everolimus therapy from 2014 to 2021 were retrospectively identified. All patients underwent regular plasma monitoring of everolimus trough levels to avoid toxicity and assess adherence. Special attention was paid to the clinical and biochemical occurrence of everolimus-related adverse events.

We report six difficult-to-treat AIH patients who received everolimus therapy for 8-46 months (median 28 months). No side effects were reported when everolimus plasma trough levels were in the therapeutic range. Liver transaminases improved in 5 of 6 patients at everolimus introduction and significantly decreased at the last follow-up (FU) in our cohort (P < 0.05). None of our patients achieved complete biochemical remission at the last FU and 3 of 6 admitted to have suboptimal adherence to therapy.

Our data bring preliminary safety for the use of everolimus as a second-/third-line therapy in pediatric AIH. Although liver transaminases improved in our cohort, prospective studies are needed to determine if everolimus can induce long-term remission.