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

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Abstract

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.

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Abbreviations

AASLD:

American Association for the Study of Liver Disease

ANOVA:

Analysis of variance

AR:

Arkansas

AUROC:

Area under the receiving operating characteristic

CFF:

Critical flicker frequency

CRT:

Continuous reaction time

CHE:

Convert hepatic encephalopathy

EASL:

European Association for the Study of the Liver

EEG:

Electroencephalogram

HE:

Hepatic encephalopathy

HCV:

Hepatitis C virus

HR:

Hazards ratio

ICT:

Inhibitory control test

IRB:

Institutions Review Board

OH:

Ohio

OHE:

Overt hepatic encephalopathy

MELD:

Model for end-stage liver disease

MMSE:

Mini-mental state examination

NASH:

Mon-alcoholic liver disease

PHES:

Psychometric Hepatic Encephalopathy Score

StE:

Stroop EncephalApp

US:

United States

VA:

Virginia

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Andres Duarte-Rojo, Christopher R. Flud & Jagpal S. Klair

  2. Division of Internal Medicine and Gastroenterology, Cleveland Clinic, Cleveland, OH, USA

    Sanath Allampati

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

    Leroy R. Thacker

  4. Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, 1201 Broad Rock Boulevard, Richmond, Virginia, 23249, USA

    Kavish R. Patidar, Melanie B. White, Douglas M. Heuman, Edith A. Gavis & Jasmohan S. Bajaj

  5. Psychiatry, Virginia Commonwealth University, Richmond, Virginia, USA

    James B. Wade

Authors
  1. Andres Duarte-Rojo
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  2. Sanath Allampati
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  3. Leroy R. Thacker
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  4. Christopher R. Flud
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  5. Kavish R. Patidar
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  6. Melanie B. White
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  7. Jagpal S. Klair
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  8. Douglas M. Heuman
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  9. James B. Wade
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  10. Edith A. Gavis
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  11. Jasmohan S. Bajaj
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Corresponding author

Correspondence to Jasmohan S. Bajaj.

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Ethical approval

All research was performed after IRB approval in all centers.

Disclosures

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.

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Key Points

• When testing for covert hepatic encephalopathy (HE) in multi-center studies, it is recommended to use consensus diagnosis based on two psychometric tests.

• Prevalence of covert HE shows wide variation depending on testing strategy.

• Use of two-test consensus strategy does not outperform single testing when prediction of future overt HE is used as the endpoint.

• In this multi-center study, single testing with Stroop EncephalApp or PHES was the most efficient way to identify and prognosticate covert HE.

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Duarte-Rojo, A., Allampati, S., Thacker, L.R. et al. Diagnosis of covert hepatic encephalopathy: a multi-center study testing the utility of single versus combined testing. Metab Brain Dis 34, 289–295 (2019). https://doi.org/10.1007/s11011-018-0350-z

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