Published online Jun 24, 2014. doi: 10.5500/wjt.v4.i2.122
Revised: April 14, 2014
Accepted: May 29, 2014
Published online: June 24, 2014
Processing time: 147 Days and 5.8 Hours
AIM: To assess our experience with the use and management of everolimus-based regimens post-liver transplantation and to redefine the potential role of this drug in current clinical practice.
METHODS: From October 1988 to December 2012, 1023 liver transplantations were performed in 955 patients in our Unit. Seventy-four patients (7.74%) received immunosuppression with everolimus at some time post-transplantation. Demographic characteristics, everolimus indication, time elapsed from transplantation to the introduction of everolimus, doses and levels administered, efficacy, side effects, discontinuation and post-conversion survival were analyzed.
RESULTS: Mean age at the time of conversion to everolimus was 57.7 ± 10 years. Indications for conversion were: refractory rejection 31.1%, extended hepatocellular carcinoma in explanted liver 19%, post-transplant hepatocellular carcinoma recurrence 8.1%, de novo tumour 17.6%, renal insufficiency 8.1%, severe neurotoxicity 10.8%, and others 5.4%. Median time from transplantation to introduction of everolimus was 6 mo (range: 0.10-192). Mean follow-up post-conversion was 22 ± 19 mo (range: 0.50-74). The event for which the drug was indicated was resolved in 60.8% of patients, with the best results in cases of refractory rejection, renal insufficiency and neurotoxicity. Results in patients with cancer were similar to those of a historical cohort treated with other immunosuppressants. The main side effects were dyslipidemia and infections. Post-conversion acute rejection occurred in 14.9% of cases. The drug was discontinued in 28.4% of patients.
CONCLUSION: Everolimus at low doses in combination with tacrolimus is a safe immunosuppressant with multiple early and late indications post-liver transplantation.
Core tip: Everolimus has a completely different mechanism of action to that of current basal calcineurine inhibitors used worldwide in liver transplantation. This immunosuppressant has a good profile for patients with pre- and post transplant renal dysfunction, one of the main concerns nowadays. It has also a promising role in cancer patients which is common in liver transplantation, either as an underlying disease (hepatocarcinoma in cirrhosis), or as de novo developing tumors. We present our off-protocol experience with partial/total and early/late conversion to everolimus, highlighting its efficacy and safety in fitting with the different emerging scenarios after liver transplantation.