Department of gastroenterology and hepatology, Hospital Clinico Universitario Lozano Blesa, Zaragoza, Spain.
Fundación Instituto Investigacion Sanitaria (IIS) Aragón, Zaragoza, Spain.
Transplantation. 2019 Aug;103(8):e211-e215. doi: 10.1097/TP.0000000000002750.
Calcineurin inhibitor-induced neurotoxicity (CIIN) is a common and debilitating side effect after liver transplantation (LT). Risk factors and impact on patient outcomes are not well defined. Our aim was to assess the incidence, risk factors, and clinical outcomes of CIIN.
We retrospectively analyzed 175 LTs performed at our center between January 2010 and September 2016. Donor and recipient demographics as well as clinical variables pre-LT, intra-LT, and post-LT were assessed. All patients were on once-daily prolonged-release tacrolimus.
CIIN was described in 37 (21.4%) recipients. In univariate analysis, history of hepatic encephalopathy (P = 0.033), immunosuppressant treatment protocol (P = 0.041), donor age (P = 0.002), and pre-LT sodium serum levels (P = 0.004) were associated with CIIN. Patients undergoing LT for hepatocellular carcinoma had lower rates of CIIN (P = 0.040). In multivariate analysis, hepatic encephalopathy (odds ratio [OR], 2.728; 95% confidence interval [CI], 1.098-6.779; P = 0.031), pre-LT serum sodium levels (OR, 1.118 per mEq/L increase, 95% CI, 1.021-1.224; P = 0.016), and donor age (OR, 1.032 per y increase; 95% CI, 1.004-1.062; P = 0.027) were independent risk factors for developing CIIN. In the CIIN group, patients had longer intensive care unit (P = 0.024) and hospital (P = 0.008) stays and more changes in immunosuppressive treatment (54.1% vs 20.4%; P < 0.001).
Neurotoxicity remains frequent in patients on once-daily prolonged-release tacrolimus. Antecedents of hepatic encephalopathy, pre-LT sodium serum levels, and donor age are independent risk factors for developing CIIN after LT. CIIN is associated with longer hospital stays and changes in immunosuppressive treatment.
钙调神经磷酸酶抑制剂诱导的神经毒性（CIIN）是肝移植（LT）后常见且使人虚弱的副作用。风险因素及其对患者预后的影响尚不清楚。我们的目的是评估 CIIN 的发生率、风险因素和临床结果。
我们回顾性分析了 2010 年 1 月至 2016 年 9 月在我们中心进行的 175 例 LT。评估了供体和受体的人口统计学特征以及 LT 前、LT 期间和 LT 后的临床变量。所有患者均接受每日一次的延长释放他克莫司治疗。
37 例（21.4%）受者出现 CIIN。在单因素分析中，肝性脑病史（P = 0.033）、免疫抑制剂治疗方案（P = 0.041）、供体年龄（P = 0.002）和 LT 前血清钠水平（P = 0.004）与 CIIN 相关。因肝细胞癌行 LT 的患者 CIIN 发生率较低（P = 0.040）。多因素分析显示，肝性脑病（优势比 [OR]，2.728；95%置信区间 [CI]，1.098-6.779；P = 0.031）、LT 前血清钠水平（OR，每增加 1 mEq/L 增加 1.118，95%CI，1.021-1.224；P = 0.016）和供体年龄（OR，每增加 1 岁增加 1.032；95%CI，1.004-1.062；P = 0.027）是发生 CIIN 的独立危险因素。在 CIIN 组中，患者 ICU（P = 0.024）和住院（P = 0.008）时间延长，免疫抑制治疗的改变更多（54.1%比 20.4%；P < 0.001）。
在接受每日一次延长释放他克莫司治疗的患者中，神经毒性仍然很常见。肝性脑病病史、LT 前血清钠水平和供体年龄是 LT 后发生 CIIN 的独立危险因素。CIIN 与住院时间延长和免疫抑制治疗改变有关。
