Safety and efficacy of everolimus as a rescue therapy in autoimmune hepatitis

In autoimmune hepatitis (AIH) some patients fail to respond to first-line immunosuppression or develop treatment-related malignancies requiring alternative treatments. Rapamycin (mTOR) inhibitors may be an alternative, but available data is limited.

We conducted a retrospective analysis of patients with AIH treated at our tertiary center between 2020 and 2025. Everolimus was administered either due to non-response to previous immunosuppressive therapies (cohort 1) or due to non-melanoma skin cancer (NMSC) during remission with conventional immunosuppressives (cohort 2).

Twenty-one patients were included (16 females, age range 28 - 80 years). Among 14 patients in cohort 1, therapy with everolimus was discontinued due to mild adverse effects (3 patients) or lack of response (2 patients). In the remaining 9 patients a significant reduction of AST was achieved after 3 months and persisted after 6 and 12 months (all p < 0.05). ALT improved after 4 weeks, and this improvement also persisted at 12 months follow-up (all p < 0.05). Prednisolone dose could be significantly reduced (p = 0.031). After 12 months of therapy with everolimus, normalization of AST was achieved in 4 (44.4%) and of ALT in 6 (66.7%) patients. Among 7 patients in cohort 2, everolimus was discontinued due to moderate adverse effects in 4 patients. All patients who tolerated everolimus (3 of 7, 42.9%) remained in remission.

In the largest cohort to date, we demonstrate a response to everolimus in refractory AIH. Everolimus represents a treatment option in AIH patients with malignancies but warrants monitoring of side effects.