Background

Clinical trials in liver transplant (LTX) patients with randomization on day 30 to everolimus (EVR) show a benefit in renal function compared to calcineurin inhibitor (CNI) standard therapy. This late randomization was required due to a black box warning for hepatic artery thrombosis in trials using sirolimus, although no evidence existed with the use of everolimus based on phase II trials in LTX. Here we report our experience with EVR for different indications immediately after LTX in a large number of patients.

Methods

Retrospective analysis of all adult LTX patients (2007-2012) in whom EVR was started within 3 month after LTX, divided in groups with de novo (≤5.pod) and delayed (>5.pod) EVR start.

Results

In 91 patients EVR therapy was started between pod 1-93 (target C0 3-8ng/ml), median duration of EVR therapy 533 days. Concomitantly patients received low dose cyclosporine or tacrolimus (59.3%/25.3%; target C0 50-80/3-5ng/ml). Main indication for EVR was impaired renal function (40%) and HCC (40%). EVR was discontinued due to adverse events (AEs) in 21 patients (23.1%), including hematological (n=5) or dermatological (n=5) side effects, wound healing disorder (n=2), hypercholesterolemia (n=2) or others (n=2). 6 patients (6.6%) developed biopsy proven acute rejection (BPAR) after a median of 47 (range 27-356) days after LTX, there of 4 cases needed steroid therapy, all successfully treated. Overall 25 patients (27.5%) died after a median follow-up of 770 days, related to septicemia (n=7), cardiorespiratory failure (n=7) or HCC recurrence (n=4). Comparing patients with de novo (n=50) or delayed (n=41) EVR start, we found no significant differences in terms of AEs, BPAR or death (p=0.110-0.355). Wound infections or hernia were not more frequent in the group of patients with de novo (22%/22%) versus delayed EVR start (9.4%/29.3%). Renal function measured by creatinine/GFR was not different between both groups (de novo 1.2mg/dl/56.4ml/min/1.73m2; delayed 1.1mg/dl/66ml/min/1.73m2) and remained stable during follow-up (de novo 1.6mg/dl/45.5ml/min/1.73m2; delayed 1.2mg/dl/57.4ml/min/1.73m2; p=0.092-0.210).

Conclusion

Our data show that EVR applied with very low dose CNI directly after LTX is safe and very effective resulting in a low rejection rate with the benefit of preserving renal function. There was no difference in wound healing complications between patients exposed to de novo or delayed EVR start.

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