External Validation of EncephalApp Stroop Test to Screen Minimal Hepatic Encephalopathy Patients with Nonalcoholic Cirrhosis

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.