Safety and efficacy of everolimus initiation from the first month after liver transplantation: A systematic review and meta-analysis

IntroductionEverolimus, a selective inhibitor of mamalian target of rapamycin (mTORi), is considered to be an alternative immunosuppressive regimen in the liver transplantation (LT) setting. However, most of the transplant centers avoid its early use (i.e., during the first month) after LT mainly due to safety issues. MethodsWe searched for all articles published between 01/2010 and 7/2022 to evaluate the effectiveness and safety of initial/early administration of everolimus after LT. ResultsSeven studies (three randomized controlled trials and four prospective cohort studies) were included: initial/early everolimus-including therapy (group 1) was used in 512 (51%) and calcineurin inhibitor (CNI) based therapy (group 2) in 494 (49%) patients. No significant difference was found between group 1 and group 2 patients regarding the rates of biopsy-proven acute rejection episodes (Odds Ratio [OR]: 1.27, 95% CI: .67-2.41, p = .465) and hepatic artery thrombosis (OR: .43, 95% CI: .09-2.02, p = .289). Everolimus was associated with higher rates of dyslipidemia (14.2% vs. 6.8%, p = .005) and incisional hernia (29.2% vs. 10.1%, p < .001). Finally, no difference was found between the two groups regarding recurrence of hepatocellular carcinoma (Risk Rates [RR]: 1.22 95%CI: .66-2.29, p = .524) and mortality (RR: .85 95%CI: .48-1.50, p = .570). ConclusionUse of initial/early everolimus seems to be effective with a satisfactory safety profile, making its administration a reasonable therapeutic option in the LT setting.