Casanovas T, Argudo A, Peña-Cala M C
Unitat de Trasplantament Hepàtic, Servei d'Aparell Digestiu, Hospitalet de Llobregat, Institut d'Investigació Biomèdica de Bellvitge, Barcelona, Spain.
Transplant Proc. 2011 Jul-Aug;43(6):2216-9. doi: 10.1016/j.transproceed.2011.06.015.
Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been used in acute and chronic treatment of kidney and heart transplants. There is scarce information regarding its use in liver transplant recipients, although everolimus may be a useful alternative for selected cases.
The objective of this study was to study the clinical, biochemical, and pathological features of patients to whom everolimus was added based upon defined clinical profiles.
This study was prospective observational ongoing study to evaluate the effectiveness and safety of everolimus alone or in combination with low doses of a calcineurin inhibitor (CNI). Chronic liver transplant recipients without contraindications to everolimus were defined based upon 7 profiles of complications. The initial everolimus dose (0.25 mg every 12 hours) was overlapped during conversion, measuring blood levels and evaluating clinical tolerance. Routine monitoring was performed to obtain immunosuppressant blood levels near the lower limit of the therapeutic range.
The 35 patients' including 17 men and 18 women, had an overall mean age of 61 ± 10 years with a mean follow-up of 34 months. The everolimus treatment lasted 20 months (range, 6-60). The indication for everolimus conversion were as follows: renal insufficiency (45.7%), no response to hepatitis C virus (HCV) treatment (42.9%), autoimmune hepatitis associated with interferon (8.5%), de novo autoimmune hepatitis (25.5%), de novo tumor (37.1%), neurotoxicity (14.3%), or side effects to rapamycin treatment (5.7%). Patients may have presented more than one indication. Effectiveness was assessed based upon improved liver (48.6%) or renal function (31.25% with renal insufficiency) or withdrawal of prednisone (100% of 10 patients receiving prednisone). CNI was withdrawn from 48.6% of patients due to de novo tumors or neurotoxicity. The side effect were as follows: anemia, leukopenia, or thrombocytopenia (11.4%) or dyslipidemia (27.3%). The survival rate was 94.3%.
Administration of everolimus to chronic liver transplants enhanced therapeutic options in the long term recipients when applied for predefined clinical indications and administrated with dose adjustments based on serial monitoring of exposure.
依维莫司是一种雷帕霉素靶蛋白（mTOR）抑制剂，已用于肾移植和心脏移植的急性和慢性治疗。尽管依维莫司可能是某些特定病例的有用替代药物，但关于其在肝移植受者中的应用信息却很少。
本研究的目的是基于明确的临床特征，研究添加依维莫司的患者的临床、生化和病理特征。
本研究是一项前瞻性观察性持续研究，旨在评估依维莫司单独使用或与低剂量钙调神经磷酸酶抑制剂（CNI）联合使用的有效性和安全性。根据7种并发症情况确定无依维莫司使用禁忌的慢性肝移植受者。在转换过程中，初始依维莫司剂量（每12小时0.25毫克）相互重叠，同时检测血药浓度并评估临床耐受性。进行常规监测以获取接近治疗范围下限的免疫抑制剂血药浓度。
35例患者（17例男性和18例女性）的总体平均年龄为61±10岁。平均随访34个月。依维莫司治疗持续20个月（范围为6-60个月）。依维莫司转换的适应证如下：肾功能不全（45.7%）、丙型肝炎病毒（HCV）治疗无反应（42.9%）、与干扰素相关的自身免疫性肝炎（8.5%）、新发自身免疫性肝炎（25.5%）、新发肿瘤（37.1%）、神经毒性（14.3%）或对雷帕霉素治疗的副作用（5.7%）。患者可能有不止一种适应证。根据肝功能改善（48.6%）或肾功能改善（肾功能不全患者中为31.25%）或停用泼尼松（10例接受泼尼松治疗的患者中100%）来评估疗效。由于新发肿瘤或神经毒性，48.6%的患者停用了CNI。副作用如下：贫血、白细胞减少或血小板减少（11.4%）或血脂异常（27.3%）。生存率为94.3%。
对于慢性肝移植患者，当依维莫司用于预定义的临床适应证并根据暴露情况的连续监测进行剂量调整时，从长期来看可增加治疗选择。
