Diagnosis of Minimal Hepatic Encephalopathy Using Stroop EncephalApp

A Multicenter US-Based, Norm-Based Study

Sanath Allampati, MD; Andres Duarte-Rojo, MD; Leroy R. Thacker, PhD; Kavish R. Patidar, MD; Melanie B. White, RN; Jagpal S. Klair, MD; Binu John, MD; Douglas M. Heuman, MD; James B. Wade, PhD; Christopher Flud, MD; Robert O'Shea, MD; Edith A. Gavis, RN; Ariel B. Unser, BS; Jasmohan S. Bajaj, MD


Am J Gastroenterol. 2016;111(1):78-86. 

In This Article

Abstract and Introduction


Objectives: Diagnosing minimal hepatic encephalopathy (MHE) is challenging, and point-of-care tests are needed. Stroop EncephalApp has been validated for MHE diagnosis in single-center studies. The objective of the study was to validate EncephalApp for MHE diagnosis in a multicenter study.

Methods: Outpatient cirrhotics (with/without prior overt hepatic encephalopathy (OHE)) and controls from three sites (Virginia (VA), Ohio (OH), and Arkansas (AR)) underwent EncephalApp and two gold standards, psychometric hepatic encephalopathy score (PHES) and inhibitory control test (ICT). Age-/gender-/education-adjusted values for EncephalApp based on direct norms, and based on ICT and PHES, were defined. Patients were followed, and EncephalApp cutoff points were used to determine OHE prediction. These cutoff points were then used in a separate VA-based validation cohort.

Results: A total of 437 cirrhotics (230 VA, 107 OH, 100 AR, 36% OHE, model for end-stage liver disease (MELD) score 11) and 308 controls (103 VA, 100 OH, 105 AR) were included. Using adjusted variables, MHE was present using EncephalApp based on norms in 51%, EncephalApp based on PHES in 37% (sensitivity 80%), and EncephalApp based on ICT in 54% of patients (sensitivity 70%). There was modest/good agreement between sites on EncephalApp MHE diagnosis using the three methods. OHE developed in 13% of patients, which was predicted by EncephalApp independent of the MELD score. In the validation cohort of 121 VA cirrhotics, EncephalApp directly and based on gold standards remained consistent for MHE diagnosis with >70% sensitivity.

Conclusions: In this multicenter study, EncephalApp, using adjusted population norms or in the context of existing gold standard tests, had good sensitivity for MHE diagnosis and predictive capability for OHE development.


Despite the burden on health-related quality of life, hospitalizations, and survival posed by minimal hepatic encephalopathy (MHE), its diagnosis remains a challenge.[1–4] Shorter tests or methods that can potentially be applied at point of care are needed.[5] One such test, the Stroop EncephalApp App, has been studied in a single-center experience with good sensitivity and specificity for the diagnosis of MHE.[6] The performance on this App changes with the underlying disease state and is correlated with driving simulation performance.[7] However, multicenter studies for the detection of MHE are lacking, especially in the United States.[1] This is further complicated by the lack of norms for performance on the gold standard tests such as the psychometric hepatic encephalopathy scale (PHES) and inhibitory control tests (ICTs) in healthy US residents beyond single-center studies.[8,9] This has hampered efforts to diagnose MHE using any means, either gold standards performed using psychological expertise or using point-of-care tests.[10]

Therefore, the aims of this current study were to (1) define norms for Stroop EncephalApp in the United States based on healthy control norms, (2) define the relationship between EncephalApp with current gold standards, (3) determine the ability of EncephalApp to predict overt hepatic encephalopathy (OHE) development, and (4) validate the EncephalApp values generated in a separate validation cohort of patients with cirrhosis.