Mediterranean Institute for Transplantation and High Specialization Therapies, University of Pittsburgh Medical Center in Italy, Palermo, Italy.
Liver Transpl. 2011 Nov;17(11):1279-85. doi: 10.1002/lt.22383.
Central nervous system (CNS) complications are common after liver transplantation (LT). According to the literature, the most common causes are infections and the neurotoxicity of immunosuppressive drugs (cyclosporine and tacrolimus). The aim of this study was to evaluate the incidence, clinical presentations, etiologies, and outcomes of CNS complications in a series of 395 consecutive LT recipients whose immunosuppression regimen was designed for low tacrolimus blood levels. An analysis of the 12-hour trough concentrations of tacrolimus in the study population showed that the target drug levels, which were designed to maintain minimal immunosuppression, were usually achieved. In all, 64 patients (16.2%) developed major neurological symptoms (37 within 30 days of LT). None of the observed CNS complications were caused by infections (viral, bacterial, or fungal), and only 3 of the 395 patients (0.8%) received a diagnosis of tacrolimus-related leukoencephalopathy. Cerebrovascular disease was identified in 15 patients (3.8%; 8 had cerebral hemorrhages, 5 had ischemic strokes, and 2 had subdural hemorrhages). Pontine myelinolysis was found in 2 patients (0.5%). Notably, no clear cause was identified for the remaining 44 cases (11.1%): brain imaging was negative for 22 cases, and diffuse hypoxic changes were present for the other 22. CNS complications were significantly associated with a reduction in 3-month patient survival (88.8% versus 95.4%) and 5-year patient survival (57.3% versus 84.1%). Among the pretransplant variables that were analyzed, the incidence of portosystemic encephalopathy, the peak serum bilirubin levels, and the lowest serum total cholesterol levels were significantly different between the 64-patient group with CNS complications and the asymptomatic group of 331 patients.
中枢神经系统（CNS）并发症在肝移植（LT）后很常见。根据文献，最常见的原因是感染和免疫抑制剂（环孢素和他克莫司）的神经毒性。本研究旨在评估一系列 395 例连续 LT 受者 CNS 并发症的发生率、临床表现、病因和结局，这些受者的免疫抑制方案旨在设计为低他克莫司血药浓度。对研究人群中他克莫司 12 小时谷浓度的分析表明，旨在维持最低免疫抑制的目标药物水平通常得以实现。共有 64 例患者（16.2%）出现主要神经症状（37 例发生在 LT 后 30 天内）。观察到的 CNS 并发症均不是由感染（病毒、细菌或真菌）引起的，在 395 例患者中只有 3 例（0.8%）诊断为他克莫司相关性脑白质病。15 例（3.8%；8 例脑出血，5 例缺血性中风，2 例硬膜下血肿）发现脑血管疾病。2 例（0.5%）发现桥脑髓鞘溶解症。值得注意的是，其余 44 例（11.1%）的原因仍不明确：22 例脑影像学检查结果阴性，其余 22 例存在弥漫性缺氧改变。CNS 并发症与 3 个月患者生存率（88.8%比 95.4%）和 5 年患者生存率（57.3%比 84.1%）显著降低相关。在分析的移植前变量中，CNS 并发症组和无症状的 331 例患者组之间，门静脉系统脑病的发生率、血清胆红素峰值和血清总胆固醇最低水平存在显著差异。
