Everolimus is safe within the first month after liver transplantation

Abstract

Background & aims: Sirolimus should not be started within the first month after liver transplantation (LT) because of an increased risk of adverse outcomes. The evidence regarding everolimus is lacking but the manufacturer transposed the same warning. We aimed to evaluate the safety of everolimus started within the first month after LT.

Methods: A consecutive cohort 187 LT patients (2009-2013) with a tacrolimus-based immunosuppression was evaluated. Patients starting everolimus within the first month after LT (n = 33; 17.6%) were compared with those starting everolimus thereafter (n = 25; 13.4%) or not receiving everolimus (n = 129; 69%). The median follow-up after LT was 21 months (IQR 7-36). Prospective outcomes were evaluated by using Kaplan-Meier curves and Cox's regression.

Results: The incidence of hepatic artery thrombosis was not significantly different in patients early treated with everolimus when compared with the remaining cohort (0% vs 9.1%; p = 0.12). Other vascular complications occurred in 9.1% of patients with early everolimus vs 7.3% in the remaining cohort (p = 0.72). No wound healing complications were detected with early everolimus. There were similar rates of incisional hernia (p = 0.31), infections (p = 0.15), renal impairment (p = 0.37), and histologically-proven acute rejection (p = 0.24) between groups. The rates of hyperlipidemia were increased with early everolimus (29.9% vs 16.5% at 3 years; p = 0.018). Graft loss and mortality rates were similar between groups (p = 0.34 and p = 0.94 respectively), after adjusting for possible confounding factors.

Conclusions: Everolimus combined with reduced tacrolimus proved to be safe within the first month after LT. Future trials may be allowed to implement everolimus early after LT.

Keywords: Everolimus; Hepatic artery thrombosis; Immunosuppression; Liver transplantation; Safety; mTOR.