Everolimus-based immunosuppression in liver transplant recipients: a single-centre experience
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Everolimus, a mammalian target of rapamycin inhibitor, has been shown to reduce growth factor-mediated cell proliferation, but data regarding its effectiveness and impact on renal function and recurrence of hepatocellular carcinoma (HCC) in liver transplant (LT) recipients are limited.
We evaluated LT recipients with a calcineurin inhibitor (CNI)-based immunosuppression regimen in whom everolimus treatment was initiated. The changes in laboratory data, including glomerular filtration rate (GFR), compared to the baseline (i.e. the day of everolimus conversion), were assessed.
Totally, 44 consecutive patients (32 men, age 55 ± 7 years) were commenced on everolimus [indications: renal dysfunction post-LT (16 patients, group 1); prevention of HCC recurrence (21 patients) or others (7 patients), group 2] at 6 months (range 1–206) post-LT. After 48 (range 12–76) months, all patients were alive without any rejection episodes. Compared to group 2 patients, group 1 patients had significantly greater improvement in renal function (DGFR: 12 ± 5 vs. −0.4 ± 0.2 ml/min, p = 0.02). GFR at baseline (OR 0.08, p = 0.002) and the combination of everolimus + MMF (OR 0.14, p = 0.024) were the factors independently associated with improvement in renal function. Finally, HCC recurrence was observed less frequently in the everolimus group of patients (n = 21) compared to the CNI-historical control group (n = 22) with HCC before LT [0/21 (0 %) vs. 4/22 (18.5 %), log rank p = 0.055), although the two groups of recipients had similar baseline characteristics and follow-up.
Everolimus is effective and is associated with low rates of HCC recurrence and improvement of renal function in LT recipients.
KeywordsEverolimus Liver transplantation Mammalian target of rapamycin inhibitor Renal function Hepatocellular carcinoma
Glomerular filtration rate
Mammalian target of rapamycin
Compliance with ethical requirements and Conflict of interest
Εvangelos Cholongitas, Eleni Theocharidou, Ioannis Goulis, Nikolaos Antoniadis, Ioannis Fouzas, George Imvrios, Olga Giouleme, Vasilios Papanikolaou, Evangelos Akriviadis, and Themistoklis Vasiliadis declare that all procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 . Informed consent was obtained from all patients for being included in the study. Evangelos Cholongitas, John Goulis, Evangelos Akriviadis, and Themistoklis Vasiliadis have served as lecturers for Gilead, Novartis and Bristol-Meier Squibb. Eleni Theocharidou, Ioannis Goulis, Nikolaos Antoniadis, Ioannis Fouzas, George Imvrios, Olga Giouleme, and Vasilios Papanikolaou have no conflicts of interest.