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Diagnosis of Minimal Hepatic Encephalopathy Using Stroop EncephalApp: A Multicenter US-Based, Norm-Based Study

Allampati, Sanath MD1; Duarte-Rojo, Andres MD2; Thacker, Leroy R PhD3; Patidar, Kavish R MD4; White, Melanie B RN4; Klair, Jagpal S MD2; John, Binu MD1; Heuman, Douglas M MD4; Wade, James B PhD5; Flud, Christopher MD2; O’Shea, Robert MD1; Gavis, Edith A RN4; Unser, Ariel B BS4; Bajaj, Jasmohan S MD4

American Journal of Gastroenterology: January 2016 - Volume 111 - Issue 1 - p 78–86
doi: 10.1038/ajg.2015.377

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.

1Internal Medicine and Gastroenterology, Cleveland Clinic, Cleveland, Ohio, USA

2University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

3Family and Community Health Nursing and Biostatistics, Richmond, Virginia, USA

4Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA

5Psychiatry, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA

Correspondence: Jasmohan S. Bajaj, MD, MS, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, 1201 Broad Rock Boulevard, Richmond, Virginia 23249, USA. E-mail:

SUPPLEMENTARY MATERIAL accompanies this paper at

Received 02 July 2015; accepted 02 October 2015

Guarantor of the article: Jasmohan S. Bajaj, MD, MS.

Specific author contributions: J.S.B., A.D.-R., and S.A. were responsible for planning of this study; M.B.W., S.A., A.D.-R., J.S.B., C.F., J.S.K., M.B.W., and A.B.U. were involved in testing and recruitment; R.O.S., B.J., and E.A.G. were involved in recruitment; J.B.W. was involved in critical revisions and drafting, and L.R.T. performed the statistical analysis.

Financial support: NIH grant NIDDK RO1DK087913 and UL1RR031990 from the National Center for Research Resources and McGuire Research Institute. The funders had no role in the data collection, study activities, or the decision to publish.

Potential competing interests: None.

© The American College of Gastroenterology 2016. All Rights Reserved.
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