Jiang Ting-Ting, Liu Xiao-Li, Yu Hao, Sun Ya-Xuan, Zhou Jia-Yan, Yang Zhi-Yun, Chen Guang
Center of Integrative Medicine, Beijing Ditan Hospital Affiliated to Capital Medical University, Beijing 100015, China.
T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, United States.
World J Hepatol. 2024 Dec 27;16(12):1450-1457. doi: 10.4254/wjh.v16.i12.1450.
Neurocognitive impairment, including minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy, is one of the most common complications of all types of primary liver diseases, such as hepatitis B, biliary cholangitis, and autoimmune hepatitis. The EncephalApp Stroop test is a smartphone application-based test that is time-saving for MHE screening. However, neurocognitive impairment is different between alcoholic cirrhosis patients and nonalcoholic cirrhosis patients, so the cutoff value for MHE diagnosis might be inflated.
To validate the Stroop test in nonalcoholic cirrhosis patients.
This external validation was performed at the National Center for Infectious Diseases (Beijing). Liver cirrhosis patients aged between 18 and 65 years who voluntarily enrolled in the study and provided signed informed consent were included. The Psychometric Hepatic Encephalopathy Score (PHES) test was used as the standard diagnostic criterion for MHE. The EncephalApp Stroop test was then performed on the iPad, including two sessions of tests ("off" and "on") to measure patients' ability to differentiate between numbers and letters. We assessed the performance of the EncephalApp Stroop test in terms of the area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value, with the PHES as the standard criterion.
A total of 160 nonalcoholic cirrhosis patients were included in this validation study, including 87 (54.4%) patients without MHE and 73 (45.6%) patients with MHE. Taking the PHES as the gold standard, the EncephalApp Stroop test performed well for nonalcoholic liver cirrhosis patients in terms of "off" time [AUC: 0.85, 95% confidence interval (CI): 0.79-0.91] and "on + off" time (AUC: 0.85, 95%CI: 0.80-0.91); however, total runs of "off" session (AUC: 0.61, 95%CI: 0.52-0.69), total runs of "on" session (AUC: 0.57, 95%CI: 0.48-0.65), and "on - off" time (AUC: 0.54, 95%CI: 0.44-0.63) were comparatively low. The optimal cutoff points were "off" time > 101.93 seconds and "on + off" time > 205.86 seconds, with sensitivities of 0.84 and 0.90, specificities of 0.77 and 0.71, positive predictive values of 0.75 and 0.72, and false-positive values of 0.85 and 0.89, respectively.
Our results suggest that different cutoffs should be used for the EncephalApp Stroop tool for MHE screening between alcoholic and nonalcoholic living patients, which is a critical check before generalization to screen for neurocognitive impairment among the whole population of chronic liver diseases.
神经认知障碍，包括轻微肝性脑病（MHE）和显性肝性脑病，是各类原发性肝病（如乙型肝炎、胆管炎和自身免疫性肝炎）最常见的并发症之一。EncephalApp Stroop测试是一种基于智能手机应用程序的测试，用于MHE筛查较为省时。然而，酒精性肝硬化患者和非酒精性肝硬化患者的神经认知障碍有所不同，因此MHE诊断的临界值可能会偏高。
验证Stroop测试在非酒精性肝硬化患者中的有效性。
这项外部验证在国家传染病中心（北京）进行。纳入年龄在18至65岁之间自愿参加本研究并签署知情同意书的肝硬化患者。采用心理测量肝性脑病评分（PHES）测试作为MHE的标准诊断标准。然后在iPad上进行EncephalApp Stroop测试，包括两个测试环节（“关闭”和“开启”），以测量患者区分数字和字母的能力。我们以PHES作为标准标准，从曲线下面积（AUC）、敏感性、特异性、阳性预测值和阴性预测值方面评估EncephalApp Stroop测试的性能。
本验证研究共纳入160例非酒精性肝硬化患者，其中87例（54.4%）无MHE，73例（45.6%）有MHE。以PHES作为金标准，EncephalApp Stroop测试在非酒精性肝硬化患者中，“关闭”时间（AUC：0.85，95%置信区间[CI]：0.79 - 0.91）和“开启+关闭”时间（AUC：0.85，95%CI：0.80 - 0.91）表现良好；然而，“关闭"环节的总次数（AUC：0.61，95%CI：0.52 - 0.69）、“开启”环节的总次数（AUC：0.57，95%CI：0.48 - 0.65）以及“开启-关闭”时间（AUC：0.54，95%CI：0.44 - 0.63）相对较低。最佳临界值为“关闭”时间>101.93秒和“开启+关闭”时间>205.86秒，敏感性分别为0.84和0.90，特异性分别为0.77和0.71，阳性预测值分别为0.75和0.72，假阳性值分别为0.85和0.89。
我们的结果表明，对于酒精性和非酒精性肝病患者，在使用EncephalApp Stroop工具进行MHE筛查时应采用不同的临界值，这是在推广用于筛查慢性肝病全人群神经认知障碍之前的关键核查步骤。
