Diagnosis of covert hepatic encephalopathy: a multi-center study testing the utility of single versus combined testing
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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.
KeywordsNeuropsychological 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
Hepatitis C virus
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
Compliance with ethical standards
All research was performed after IRB approval in all centers.
No potential conflict of interest.
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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