Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University/McGuire VA Medical Center, Richmond, VA 23249, USA.
Liver Transpl. 2012 Oct;18(10):1179-87. doi: 10.1002/lt.23484.
Psychiatric disorders and medications may affect the cognitive performance of patients with cirrhosis and complicate the diagnosis and prediction of hepatic encephalopathy (HE). The aim of this study was to study the association of psychoactive medications with cognitive performance and their effects on the ability of tests to predict HE development in patients with cirrhosis referred for transplant evaluation. Cirrhosis details, psychiatric disorders, psychoactive medications, and any history of prior HE were recorded for patients with cirrhosis at 2 transplant centers. Patients were followed until the development of HE. Five cognitive tests--number connection test A (NCT-A), number connection test B, the digit symbol test (DST), the block design test, and the inhibitory control test (ICT)--were administered. A high lure score and a low ICT target score indicated poor performance. The cognitive performances of patients with psychiatric disorders/medications and patients without them were compared. A proportional hazards model was created with the time to HE as the outcome, and it was based on demographics, psychoactive medications, cirrhosis details, and individual cognitive scores. Patients with prior HE and patients without prior HE were then studied separately. One hundred fifty-five patients with a mean age of 57.5 ± 6.2 years and a mean Model for End-Stage Liver Disease (MELD) score of 15.1 ± 6.2 were included [prior HE, 48%; diabetes, 34%; selective serotonin reuptake inhibitors (SSRIs), 32%; opioids, 19%; and antipsychotics, 10%]. Prior HE and antipsychotics (but not opioids or diabetes) were associated with worse cognition. SSRI users had better NCT-A and DST performance. One hundred forty-eight patients were followed for a median of 182.5 days; 58 developed HE at a median of 99 days after inclusion. In the entire group, the model showed that prior HE (hazard ratio = 4.13), the MELD score (hazard ratio = 1.07), and a high lure score (hazard ratio = 1.04) decreased the time to HE, whereas the use of SSRIs (hazard ratio = 0.42), a high target score (hazard ratio = 0.95), and a high sodium level (hazard ratio = 0.89) increased the time to HE. For patients without prior HE, the MELD score (hazard ratio = 1.25) and lures (hazard ratio = 1.09) predicted the time to HE. Lures (hazard ratio = 1.03), targets (hazard ratio = 0.96), and sodium (hazard ratio = 0.87) were associated with the time to HE in patients with prior HE. In conclusion, cognitive tests (particularly the ICT) remain valid predictors of HE in the face of psychiatric diseases and medications. SSRI use is associated with better cognitive performance and a reduced likelihood of developing HE.
精神障碍和药物治疗可能会影响肝硬化患者的认知表现，并使肝性脑病 (HE) 的诊断和预测复杂化。本研究旨在研究精神药物与认知表现的关系，以及它们对预测肝硬化患者 HE 发展的测试能力的影响，这些患者因移植评估而被转介。在 2 家移植中心记录了肝硬化患者的肝硬化细节、精神障碍、精神药物治疗以及任何既往 HE 病史。对患者进行随访，直至发生 HE。进行了 5 项认知测试——数字连接测试 A（NCT-A）、数字连接测试 B、数字符号测试（DST）、方块设计测试和抑制控制测试（ICT）。高诱饵分数和低 ICT 目标分数表示表现不佳。比较了有精神疾病/药物治疗的患者和没有精神疾病/药物治疗的患者的认知表现。创建了一个以 HE 发生时间为结果的比例风险模型，该模型基于人口统计学、精神药物治疗、肝硬化细节和个体认知评分。然后分别研究了有既往 HE 和无既往 HE 的患者。共纳入 155 名平均年龄为 57.5 ± 6.2 岁、平均终末期肝病模型（MELD）评分为 15.1 ± 6.2 的患者[既往 HE 占 48%；糖尿病占 34%；选择性 5-羟色胺再摄取抑制剂（SSRIs）占 32%；阿片类药物占 19%；抗精神病药物占 10%]。既往 HE 和抗精神病药物（但不是阿片类药物或糖尿病）与认知能力下降有关。SSRIs 使用者的 NCT-A 和 DST 表现更好。148 名患者中位随访 182.5 天；58 名患者在纳入后中位 99 天发生 HE。在整个组中，该模型显示既往 HE（危险比=4.13）、MELD 评分（危险比=1.07）和高诱饵分数（危险比=1.04）降低了 HE 发生时间，而 SSRIs 的使用（危险比=0.42）、高目标分数（危险比=0.95）和高钠水平（危险比=0.89）增加了 HE 发生时间。对于没有既往 HE 的患者，MELD 评分（危险比=1.25）和诱饵（危险比=1.09）预测了 HE 发生时间。在既往 HE 患者中，诱饵（危险比=1.03）、目标（危险比=0.96）和钠（危险比=0.87）与 HE 发生时间相关。总之，认知测试（尤其是 ICT）在存在精神疾病和药物治疗的情况下仍然是 HE 的有效预测指标。SSRIs 的使用与更好的认知表现和降低发生 HE 的可能性相关。
