Cholongitas Εvangelos, Goulis Ioannis, Theocharidou Eleni, Antoniadis Nikolaos, Fouzas Ioannis, Giakoustidis Dimitrios, Imvrios George, Giouleme Olga, Papanikolaou Vasilios, Akriviadis Evangelos, Vasiliadis Themistoklis
4th Department of Internal Medicine, Hippokration General Hospital of Thessaloniki, Medical School of Aristotle University, 49, Konstantinopoleos Street, 54642, Thessaloniki, Greece.
2nd Propedeutic Department of Internal Medicine, Hippokration Hospital, Medical School of Aristotle University, Thessaloniki, Greece.
Hepatol Int. 2014 Jan;8(1):137-45. doi: 10.1007/s12072-013-9492-6. Epub 2013 Dec 28.
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.
依维莫司是一种雷帕霉素哺乳动物靶点抑制剂,已被证明可减少生长因子介导的细胞增殖,但关于其在肝移植(LT)受者中对肾功能及肝细胞癌(HCC)复发的有效性和影响的数据有限。
我们评估了采用基于钙调神经磷酸酶抑制剂(CNI)的免疫抑制方案且开始接受依维莫司治疗的LT受者。评估了与基线(即依维莫司转换日)相比实验室数据的变化,包括肾小球滤过率(GFR)。
共有44例连续患者(32例男性,年龄55±7岁)在LT术后6个月(范围1 - 206个月)开始使用依维莫司[适应证:LT术后肾功能不全(16例患者,第1组);预防HCC复发(21例患者)或其他情况(7例患者),第2组]。48个月(范围12 - 76个月)后,所有患者均存活,无任何排斥反应。与第2组患者相比,第1组患者的肾功能改善显著更大(GFR变化值:12±5 vs. -0.4±0.2 ml/min,p = 0.02)。基线时的GFR(OR 0.08,p = 0.002)以及依维莫司 + 霉酚酸酯(MMF)联合使用(OR 0.14,p = 0.024)是与肾功能改善独立相关的因素。最后,与LT前有HCC的CNI历史对照组(n = 22)相比,依维莫司组患者(n = 21)中HCC复发的观察频率更低[0/21(0%)vs. 4/22(18.5%),对数秩检验p = 0.055],尽管两组受者的基线特征和随访情况相似。
依维莫司有效,且与LT受者中HCC复发率低及肾功能改善相关。