Covert Hepatic Encephalopathy Diagnosis With The New Stroop App (EncephalApp) Using Age-Based Cut-off ValuesJasmohan S. Bajaj1, Douglas M. Heuman1, Leroy Thacker3, Richard K. Sterling1, R. Todd Stravitz 1, Arun J. Sanyal1, Velimir A. Luketic1, Nicole Noble1,

Melanie White1, Ariel Unser1, Pamela Monteith1, Puneet Puri1, James Wade2 1Gastroenterology, Hepatology and Nutrition, 2Psychiatry, 3Biostatistics Virginia Commonwealth University and McGuire VAMC, Richmond,

BACKGROUND

• Diagnosis of covert/minimal hepatic encephalopathy (CHE) is difficult therefore a high sensitivity/specificity screening test is required.• The older Stroop App (downloaded from iTunes) has been validated for diagnosis of CHE but it needed updates to make it CHE-specific• Therefore the new EncephalApp_Stroop was created to:

• Streamline timing: removes unnecessary time wastage between stimuli and therefore to reduces total testing time),• Improves and systematizes result transmission: results are emailed in the form of Excel sheets automatically in order to prevent copying errors. • Added an iPad-ready version

• Further population norms were also required for this app

CONCLUSIONS: The new age-based cut-offs for EncephalApp_Stroop are highly sensitive for covert HE screening and could be used to guide future

testing in cirrhosis regardless of mode of administration (iPad or iPhone/iPod)

AIM To validate EncephalApp for the CHE diagnosis using age-based cut-offs and to evaluate the iPad version performance

compared to the iPod/iPhone version.

METHODS • Cirrhotics and healthy controls underwent cognitive testing using standard batteries (Number connection-A/B,(NC-A/B), digit symbol (DS), block design (BD)• Performance on ≥2 tests impaired two standard deviations beyond controls was considered CHE• Subjects were then tested on the new App. • The App has two parts;

• Stroop Off in which the subject needs to press the correct color in which # signs are presented (Figure 1A).• Stroop On in which the subject needs press the correct color in which words meaning red,green or blue are presented in discordant colors i.e. if “red” is presented in green color, the correct answer is green (Figure 1B).

RESULTS• OffTime+OnTime was correlated with age (r=0.6, p<0.0001) but not education in controls, therefore their App results were analyzed separately for those > or <45 yrs.• OffTime+OnTime(±SD) in controls <45 yrs was 119±13 sec & 146±22 sec in those>45 yrs. Therefore 2 standard deviations impaired beyond controls was >145 sec in pts <45 yrs &>190 sec in >45 yrs on OffTime+OnTime. • Cirrhosis group: OffTime+OnTime was significantly higher in CHE cirrhotic patients compared to those without regardless of whether those with prior overt HE were included or not (Figures 2A and B) and was correlated with MELD (r=0.5,p=0.004) but not age/education. Number of trials to achieve 5 correct Off (5 vs 6) or On (5 vs 6) were not different between CHE/no CHE.• CHE diagnosis: Using the age-adjusted cutoffs, 52% of patients had impaired App performance. CHE was more in those with prior OHE (94% vs no OHE 30%,p=0.0001). Using standard tests as reference sensitivity of these age-variable cut-offs was 90% while specificity was 78%.

METHODS• Time to complete 5 Off runs(OffTime) and On(OnTime) were recorded; a lower time indicates good performance. • Number of trials to achieve 5 correct runs was also recorded.• OffTime+OnTime >2 standard deviations above controls was considered impaired on EncephalApp. • Sensitivity and specificity were performed for EncephalApp using standard tests are gold standard• A group of subjects then underwent the EncephalApp on iPad or iPod in random order and their results were compared.

RESULTS• 100 controls (age 43±14 yrs, education 15±2 yrs, 50% >45 yrs age) and 132 cirrhotics (MELD 12±5, years of education 14±2) were included.• 37% of cirrhotics had prior overt HE currently controlled on rifaximin or lactulose at time of testing.• All patients underwent EncephalApp & standard testing at the same sitting. • Controls performed significantly better than cirrhotics on

• Standard tests (NC-A 23 vs 43s, NC-B 59 vs 114s, DS 78 vs 53, BD 42 vs 22, all p<0.0001) and•EncephalApp OffTime+OnTime (132 vs 206 s p<0.0001).

• We found evidence of CHE in 40% of pts on standard tests.

iPad vs iPod/iPhone: 17 subjects (8 controls and 9 cirrhotics) underwent sequential testing with these two modes of administration in random order (9 had iPad first and 8 had iPod first). There were no differences in EncephalApp results and the OffTime+OnTime were significantly correlated (Figure 3)

2A 2B

1A 1B

3

R=0.94, p<0.0001