Heits Nils, Keserovic Dalibor, Mund Niclas, Ehmke Nicola, Bernsmeier Alexander, Hendricks Alexander, Gunther Rainer, Witt Karsten, Becker Thomas, Braun Felix
Department of General, Visceral, Thoracic, Transplantation and Pediatric Surgery, University Medical Centre Schleswig-Holstein (UKSH), Kiel, Germany.
Department of Internal Medicine I, University Medical Centre Schleswig-Holstein (UKSH), Kiel, Germany.
Transplant Direct. 2017 Mar 28;3(4):e146. doi: 10.1097/TXD.0000000000000658. eCollection 2017 Apr.
Neurological disorders due to calcineurin inhibitor (CNI) treatment pose a well-known problem after liver transplantation (LTx). In this study, the impact of CNIs on cognitive functioning during maintenance therapy was analyzed. A possible improvement of cognitive functioning, compliance and health-related quality of life (HRQoL) after conversion to a once-daily tacrolimus formulation was prospectively assessed.
In a cross-section analysis cognitive functioning of living donors (LD), waiting list patients and LTx patients was tested using a 4 times trail making test (4-TTMT). In a further investigator-initiated trial a possible improvement of cognitive functioning, HRQoL and compliance after conversion to the once-daily tacrolimus formulation was prospectively assessed over 1 year. HRQoL was assessed using an EORTC-QLQ C30 questionnaire and patient's compliance was assessed by the Basel Assessment of Compliance with Immunosuppressive Medication Scales questionnaire. Correlated data were sex, age, time after surgery, liver disease, model of end-stage liver disease score, creatinine, CNI type, and CNI trough levels.
Two hundred eleven patients were included in this cross-section analysis. Twenty-seven patients agreed to participate in the investigator-initiated trial. LTx patients completed the 4-TTMT slower than living donor patients and faster than waiting list patients. Patients with twice daily cyclosporine A (CSA) formulation needed longer to finish the 4-TTMT than patients with the once-daily tacrolimus formulation. After drug conversion of a twice-daily CNI formulation to a once-daily tacrolimus formulation, CSA-treated patients needed longer to improve their cognitive functioning. HRQoL and compliance did not improve after drug conversion.
Patients with once-daily tacrolimus formulation had a better psychomotor speed than CSA-treated patients. The conversion to once-daily tacrolimus formulation significantly improved cognitive functioning, but had no impact on HRQoL or compliance.
肝移植（LTx）后，钙调神经磷酸酶抑制剂（CNI）治疗导致的神经功能障碍是一个众所周知的问题。在本研究中，分析了CNI在维持治疗期间对认知功能的影响。前瞻性评估了转换为每日一次他克莫司制剂后认知功能、依从性和健康相关生活质量（HRQoL）的可能改善情况。
在一项横断面分析中，使用4次连线测验（4-TTMT）对活体供体（LD）、等待名单患者和LTx患者的认知功能进行测试。在另一项由研究者发起的试验中，前瞻性评估了转换为每日一次他克莫司制剂后1年内认知功能、HRQoL和依从性的可能改善情况。使用欧洲癌症研究与治疗组织-QLQ C30问卷评估HRQoL，通过巴塞尔免疫抑制药物依从性评估量表问卷评估患者的依从性。相关数据包括性别、年龄、术后时间、肝脏疾病、终末期肝病模型评分、肌酐、CNI类型和CNI谷浓度。
211例患者纳入本横断面分析。27例患者同意参加研究者发起的试验。LTx患者完成4-TTMT的速度比活体供体患者慢，比等待名单患者快。每日两次环孢素A（CSA）制剂的患者完成4-TTMT所需时间比每日一次他克莫司制剂的患者长。将每日两次CNI制剂转换为每日一次他克莫司制剂后，CSA治疗的患者改善认知功能所需时间更长。药物转换后HRQoL和依从性未改善。
每日一次他克莫司制剂的患者比CSA治疗的患者具有更好的精神运动速度。转换为每日一次他克莫司制剂可显著改善认知功能，但对HRQoL或依从性无影响。
