Metabolic Brain Disease

, Volume 34, Issue 1, pp 289–295 | Cite as

Diagnosis of covert hepatic encephalopathy: a multi-center study testing the utility of single versus combined testing

  • Andres Duarte-Rojo
  • Sanath Allampati
  • Leroy R. Thacker
  • Christopher R. Flud
  • Kavish R. Patidar
  • Melanie B. White
  • Jagpal S. Klair
  • Douglas M. Heuman
  • James B. Wade
  • Edith A. Gavis
  • Jasmohan S. BajajEmail author
Original Article


Covert hepatic encephalopathy (CHE) affects cognition in a multidimensional fashion. Current guidelines recommend performing Psychometric Hepatic Encephalopathy Score (PHES) and a second test to diagnose CHE for multi-center trials. We aimed to determine if a two-test combination strategy improved CHE diagnosis agreement, and accuracy to predict overt hepatic encephalopathy (OHE), compared to single testing. Cirrhotic outpatients without baseline OHE performed PHES, Inhibitory Control Test (ICT), and Stroop EncephAlapp (StE) at three centers. Patients were followed for OHE development. Areas under the receiver operation characteristic curve (AUROC) were calculated. We included 437 patients (399 with follow-up data). CHE prevalence varied with testing strategy: PHES+ICT 18%, ICT + StE 25%, PHES+StE 29%, ICT 35%, PHES 37%, and StE 54%. Combination with best test agreement was PHES+StE (k = 0.34). Sixty patients (15%) developed OHE. Although CHE by StE showed the highest sensitivity to predict OHE, PHES and PHES+StE were more accurate at the expense of a lower sensitivity (55%, AUROC: 0.587; 36%, AUROC: 0.629; and 29%, AUROC: 0.623; respectively). PHES+ICT was the most specific (85%) but all strategies including ICT showed sensitivities in the 33–45% range. CHE diagnosis by PHES (HR = 1.79, p = 0.04), StE (HR = 1.69, p = 0.04), and PHES+StE (HR = 1.72, p = 0.04), were significant OHE predictors even when adjusted for prior OHE and MELD. Our results demonstrate that combined testing decreases CHE prevalence without improving the accuracy of OHE prediction. Testing with PHES or StE alone, or a PHES+StE combination, is equivalent to diagnose CHE and predict OHE development in a multi-center setting.


Neuropsychological test Neurophysiological test Overt hepatic encephalopathy PHES Inhibitory control test Stroop encephalapp 



American Association for the Study of Liver Disease


Analysis of variance




Area under the receiving operating characteristic


Critical flicker frequency


Continuous reaction time


Convert hepatic encephalopathy


European Association for the Study of the Liver




Hepatic encephalopathy


Hepatitis C virus


Hazards ratio


Inhibitory control test


Institutions Review Board




Overt hepatic encephalopathy


Model for end-stage liver disease


Mini-mental state examination


Mon-alcoholic liver disease


Psychometric Hepatic Encephalopathy Score


Stroop EncephalApp


United States




Compliance with ethical standards

Ethical approval

All research was performed after IRB approval in all centers.


No potential conflict of interest.

Grant support

ADR receives partial support from the University of Arkansas for Medical Sciences College of Medicine Clinician Scientist Program. This work was also partly supported by NIH RO1DK089713 and VA Merit Review CX1076 to JSB.

Supplementary material

11011_2018_350_MOESM1_ESM.docx (14 kb)
ESM 1 (DOCX 13 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Andres Duarte-Rojo
    • 1
  • Sanath Allampati
    • 2
  • Leroy R. Thacker
    • 3
  • Christopher R. Flud
    • 1
  • Kavish R. Patidar
    • 4
  • Melanie B. White
    • 4
  • Jagpal S. Klair
    • 1
  • Douglas M. Heuman
    • 4
  • James B. Wade
    • 5
  • Edith A. Gavis
    • 4
  • Jasmohan S. Bajaj
    • 4
    Email author
  1. 1.Division of Gastroenterology and HepatologyUniversity of Arkansas for Medical SciencesLittle RockUSA
  2. 2.Division of Internal Medicine and Gastroenterology, Cleveland ClinicClevelandUSA
  3. 3.Family and Community Health Nursing and BiostatisticsVirginiaUSA
  4. 4.Division of Gastroenterology, Hepatology and NutritionVirginia Commonwealth University and McGuire VA Medical CenterVirginiaUSA
  5. 5.Psychiatry, Virginia Commonwealth UniversityVirginiaUSA

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