Everolimus in clinical practice in long-term liver transplantation: an observational study

Abstract

Introduction: Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been used in acute and chronic treatment of kidney and heart transplants. There is scarce information regarding its use in liver transplant recipients, although everolimus may be a useful alternative for selected cases.

Objective: The objective of this study was to study the clinical, biochemical, and pathological features of patients to whom everolimus was added based upon defined clinical profiles.

Study design: This study was prospective observational ongoing study to evaluate the effectiveness and safety of everolimus alone or in combination with low doses of a calcineurin inhibitor (CNI). Chronic liver transplant recipients without contraindications to everolimus were defined based upon 7 profiles of complications. The initial everolimus dose (0.25 mg every 12 hours) was overlapped during conversion, measuring blood levels and evaluating clinical tolerance. Routine monitoring was performed to obtain immunosuppressant blood levels near the lower limit of the therapeutic range.

Results: The 35 patients' including 17 men and 18 women, had an overall mean age of 61 ± 10 years with a mean follow-up of 34 months. The everolimus treatment lasted 20 months (range, 6-60). The indication for everolimus conversion were as follows: renal insufficiency (45.7%), no response to hepatitis C virus (HCV) treatment (42.9%), autoimmune hepatitis associated with interferon (8.5%), de novo autoimmune hepatitis (25.5%), de novo tumor (37.1%), neurotoxicity (14.3%), or side effects to rapamycin treatment (5.7%). Patients may have presented more than one indication. Effectiveness was assessed based upon improved liver (48.6%) or renal function (31.25% with renal insufficiency) or withdrawal of prednisone (100% of 10 patients receiving prednisone). CNI was withdrawn from 48.6% of patients due to de novo tumors or neurotoxicity. The side effect were as follows: anemia, leukopenia, or thrombocytopenia (11.4%) or dyslipidemia (27.3%). The survival rate was 94.3%.

Conclusions: Administration of everolimus to chronic liver transplants enhanced therapeutic options in the long term recipients when applied for predefined clinical indications and administrated with dose adjustments based on serial monitoring of exposure.