Validation of EncephalApp, Smartphone-Based Stroop Test, for the Diagnosis of Covert Hepatic Encephalopathy

Abstract

Background & aims: Detection of covert hepatic encephalopathy (CHE) is difficult, but point-of-care testing could increase rates of diagnosis. We aimed to validate the ability of the smartphone app EncephalApp, a streamlined version of Stroop App, to detect CHE. We evaluated face validity, test-retest reliability, and external validity.

Methods: Patients with cirrhosis (n = 167; 38% with overt HE [OHE]; mean age, 55 years; mean Model for End-Stage Liver Disease score, 12) and controls (n = 114) were each given a paper and pencil cognitive battery (standard) along with EncephalApp. EncephalApp has Off and On states; results measured were OffTime, OnTime, OffTime+OnTime, and number of runs required to complete 5 off and on runs. Thirty-six patients with cirrhosis underwent driving simulation tests, and EncephalApp results were correlated with results. Test-retest reliability was analyzed in a subgroup of patients. The test was performed before and after transjugular intrahepatic portosystemic shunt placement, and before and after correction for hyponatremia, to determine external validity.

Results: All patients with cirrhosis performed worse on paper and pencil and EncephalApp tests than controls. Patients with cirrhosis and OHE performed worse than those without OHE. Age-dependent EncephalApp cutoffs (younger or older than 45 years) were set. An OffTime+OnTime value of >190 seconds identified all patients with CHE with an area under the receiver operator characteristic value of 0.91; the area under the receiver operator characteristic value was 0.88 for diagnosis of CHE in those without OHE. EncephalApp times correlated with crashes and illegal turns in driving simulation tests. Test-retest reliability was high (intraclass coefficient, 0.83) among 30 patients retested 1-3 months apart. OffTime+OnTime increased significantly (206 vs 255 seconds, P = .007) among 10 patients retested 33 ± 7 days after transjugular intrahepatic portosystemic shunt placement. OffTime+OnTime decreased significantly (242 vs 225 seconds, P = .03) in 7 patients tested before and after correction for hyponatremia (126 ± 3 to 132 ± 4 meq/L, P = .01) 10 ± 5 days apart.

Conclusions: A smartphone app called EncephalApp has good face validity, test-retest reliability, and external validity for the diagnosis of CHE.

Keywords: Minimal Hepatic Encephalopathy; Screening; Stroop Test; TIPS.

Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Comparison of OffTime+OnTime between groups, CHE: covert hepatic encephalopathy on paper-pencil tests, Ctrl: controls, mean±95% CI depicted in the bars 1A: Significantly higher OffTime+OnTime in patients with CHE than those without CHE in the entire cirrhosis group compared to controls 1B: Significantly higher OffTime+OnTime in patients with CHE than those without CHE in the patient group without prior OHE compared to controls 1C: Significantly higher OffTime+OnTime in subjects ≥45 years compared to those

Figure 1

Comparison of OffTime+OnTime between groups, CHE: covert hepatic encephalopathy on paper-pencil tests, Ctrl: controls, mean±95% CI depicted in the bars 1A: Significantly higher OffTime+OnTime in patients with CHE than those without CHE in the entire cirrhosis group compared to controls 1B: Significantly higher OffTime+OnTime in patients with CHE than those without CHE in the patient group without prior OHE compared to controls 1C: Significantly higher OffTime+OnTime in subjects ≥45 years compared to those

Figure 1

Comparison of OffTime+OnTime between groups, CHE: covert hepatic encephalopathy on paper-pencil tests, Ctrl: controls, mean±95% CI depicted in the bars 1A: Significantly higher OffTime+OnTime in patients with CHE than those without CHE in the entire cirrhosis group compared to controls 1B: Significantly higher OffTime+OnTime in patients with CHE than those without CHE in the patient group without prior OHE compared to controls 1C: Significantly higher OffTime+OnTime in subjects ≥45 years compared to those

Figure 2

ROC analysis of OffTime+OnTime against paper-pencil tests 2A: in all patients (AUC: 0.91) 2B: in patients without prior overt HE (AUC: 0.88)

Figure 2

ROC analysis of OffTime+OnTime against paper-pencil tests 2A: in all patients (AUC: 0.91) 2B: in patients without prior overt HE (AUC: 0.88)

Figure 3

Change in EncephalApp results with TIPS and hyponatremia correction 3A: OffTime+OnTime before/after TIPS placement 3B: OffTime+OnTime before/after hyponatremia correction

Figure 3

Change in EncephalApp results with TIPS and hyponatremia correction 3A: OffTime+OnTime before/after TIPS placement 3B: OffTime+OnTime before/after hyponatremia correction