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Immunosuppressive treatment with everolimus in patients after orthotopic liver transplantation: 4 years of experience.

Research paper by Michał P MP Wasilewicz, Dorota D Moczydłowska, Maciej M Janik, Michał M Grąt, Krzysztof K Zieniewicz, Joanna J Raszeja-Wyszomirska

Indexed on: 18 Nov '20Published on: 11 Sep '19Published in: Polskie Archiwum Medycyny Wewnetrznej



Abstract

Everolimus (EVL) after liver transplantation (LT) has been used to minimize calcineurin inhibitors (CNIs), optimize renal function (RF), and prevent hepatocellular carcinoma (HCC) recurrence. The aim of the study was to analyze the single-center experience with modalities of immunosuppressive treatment conversion from CNIs to EVL in LT patients. One-hundred-eight liver transplant recipients (65.7% males; mean (SD) age of 53.2 (11.1) years) were prospectively enrolled into the study. EVL+CNI were introduced with blood trough levels (3-6 and 3-5 ng/ml respectively). After 3 months, CNI was discontinued in patients who well tolerated EVL, with increased EVL dosage  (blood trough levels 6-12 ng/ml). EVL monotherapy was introduced in 32 (29.6%) LT recipients, EVL+CNI were continued in 76. However, among them during the median observation of 27 months (4-50), EVL was withdrawn in 25 (33%) due to its side effects. In EVL monotherapy group, all patients continued therapy [p<0.005], but dyslipidemia was more frequent than in EVL+CNI patients (40.6% vs. 14.5%) [p<0.03]. Creatinine levels improved significantly in both groups: EVL+CNI 1.58->1.24 mg/dl after 3 months; EVL 1.19->1.00 mg/dl respectively; the EVL group RF was better than EVL+CNI [p<0.04]. HCC recurrence was observed in both groups: EVL+CNI 9/46 (19.6%) vs. EVL 1/17 (5.9%) [p<0.01]. This study showed that conversion from CNIs to EVL after LT allowed safe weaning of CNIs and improvement in creatinine levels. We detected EVL dose-dependence of dyslipidemia and lower risk of HCC recurrence in LT patients with EVL monotherapy. Further long-term analysis is required.