Indications and Management of m-Tor Inhibitors After Liver Transplantation

摘要

AIM: To assess our experience with the use and management of m-TORi after liver transplantation. MATERIAL: From 1988 to 2007, 783 LT were performed in 725 patients. Fifty one patients (7%) received immunosuppression with m-TORi: Rapamicine 36 and Everolimus 15. Mean age was 54.8 years (r: 24-70). Indication of use, time between LT and introduction of m-TORi, efficacy, side effects and survival were analyzed. RESULTS: Indications were: refractory rejection in the context of renal insufficiency 20 (39%), renal insufficiency 5 (10%), other CNI side effects 6 (12%), extended HCC in the explanted liver 7 (14%), HCC recurrence during follow-up 7 (14%) and de novo tumor 3 (6%). Mean time between LT and m-TORi was 18 +- 29 months with a median of 3 months (r: 10 days-122 months). Mean follow-up after conversion was 14 +- 15 months (r: 0.1-72). In general, half of the patients resolved the event for which the drag was indicated. Refractory rejection was succesfully resolved in half the patients, three required re-LT and six progressed to chronic liver dysfunction with the result of five deaths due to non-resolved rejection and comorbidity. The renal insufficiency at time of conversion resolved in 11 (52%) of the 21 cases. Six out of 7 patients with recurrent HCC died at a mean follow-up of 11.5 months. Three out of 7 patients with extended HCC died at a mean follow-up of 8.2 months. The three cases of de novo tumor were coverted to m-TORi four weeks after surgery and are perfectly healthy. Half of the patients presented m-TORi-related side effects: dyslipemia in 24 (47%), infection in 9 (17.6%); diarrhea in 3 (6%), and hematologic complications in 3 (6%). Six patients (11.7%) developed acute rejection after conversion. Seventeen patients (33.3%) discontinued the drug: 6 due to inefficacy; 5 due to inter-current surgery; 3 due to resolution of the cause; and 3 due to adverse events. Patient actuarial survival was 54%, 46% and 23% at 1,3 and 5 years post-conversion. CONCLUSION: m-TORi are indicated in critical and irreversible situations where other immunosuppressants have failed. During the early stage, they are used for refractory rejection or as prophylaxis for recurrence of extended tumors. At any time, but specially in the late period, they are indicated in patients with serious CNI side effects, HCC recurrence, and de novo tumors.