Observational Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 27, 2024; 16(12): 1450-1457
Published online Dec 27, 2024. doi: 10.4254/wjh.v16.i12.1450
External validation of EncephalApp Stroop test to screen minimal hepatic encephalopathy patients with nonalcoholic cirrhosis
Ting-Ting Jiang, Xiao-Li Liu, Hao Yu, Ya-Xuan Sun, Jia-Yan Zhou, Zhi-Yun Yang, Guang Chen
Ting-Ting Jiang, Xiao-Li Liu, Hao Yu, Zhi-Yun Yang, Center of Integrative Medicine, Beijing Ditan Hospital Affiliated to Capital Medical University, Beijing 100015, China
Ya-Xuan Sun, T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, United States
Jia-Yan Zhou, School of Medicine, Stanford University, Stanford, CA 94305, United States
Guang Chen, LKS Faculty of Medicine, University of Hong Kong, Hong Kong 999077, China
Co-corresponding authors: Zhi-Yun Yang and Guang Chen.
Author contributions: Jiang TT designed and got the funding of this study; Liu XL and Yu H recruited patients; Sun YX and Zhou JY analyzed the data; Yang ZY and Chen G performed the research and drafted the manuscript, they are the co-corresponding authors of this article.
Supported by National Science Foundation of China, No. 82104781; High Level Public Health Technical Personnel Construction Project, No. leaders-02-16; Dengfeng Talent Support Program of Beijing Municipal Administration of Hospitals, No. DFL20191803; Beijing Hospitals Authority Clinical Medicine Development of Special Funding, No. ZYLX202127; Special Fund of Capital Health Research and Development, No. 2020-2-2173; and Beijing Municipal Administration of Hospitals Incubating Program, No. PZ20241802.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Beijing Ditan Hospital, Approval No. Jingdilunkezi(2020)di(037)-02.
Informed consent statement: Informed consent was obtained from each participant in this study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The raw data supporting the conclusions of this article will be made available from corresponding author upon request with academic reasons.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Guang Chen, MD, MSc, PhD, Doctor, Postdoctoral Fellow, LKS Faculty of Medicine, University of Hong Kong, No. 3 Sassoon Road, Hong Kong 999077, China. gchen91@hku.hk
Received: July 10, 2024
Revised: August 29, 2024
Accepted: September 11, 2024
Published online: December 27, 2024
Processing time: 142 Days and 7.4 Hours
Abstract
BACKGROUND

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.

AIM

To validate the Stroop test in nonalcoholic cirrhosis patients.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Keywords: Minimal hepatic encephalopathy; Nonalcoholic cirrhosis; EncephalApp Stroop test; Diagnosis; Screening

Core Tip: This study validated the EncephalApp Stroop test on screening minimal hepatic encephalopathy patients with nonalcoholic cirrhosis. The results showed that EncephalApp Stroop test was time-saving with good predictive performance on the validation dataset. This study concluded that we should use different cutoff value of EncephalApp Stroop tool on minimal hepatic encephalopathy screening between alcoholic and nonalcoholic patients, before widespread application of EncephalApp Stroop test in management of chronic liver diseases.