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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
  • 59 Downloads

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.

Keywords

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

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

Notes

Compliance with ethical standards

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.

Supplementary material

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

References

  1. Allampati S, Duarte-Rojo A, Thacker LR, Patidar KR, White MB, Klair JS, John B, Heuman DM, Wade JB, Flud C, O’Shea R, Gavis EA, Unser AB, Bajaj JS (2016) Diagnosis of minimal hepatic encephalopathy using Stroop EncephalApp: a multicenter US-based, norm-based study. Am J Gastroenterol 111:78–86CrossRefGoogle Scholar
  2. Amodio P, Campagna F, Olianas S, Iannizzi P, Mapelli D, Penzo M, Angeli P, Gatta A (2008) Detection of minimal hepatic encephalopathy: normalization and optimization of the psychometric hepatic encephalopathy score. A neuropsychological and quantified EEG study. J Hepatol 49:346–353CrossRefGoogle Scholar
  3. Amodio P, Ridola L, Schiff S et al (2010) Improving the inhibitory control task to detect minimal hepatic encephalopathy. Gastroenterology 139(510–518):518 e511–518 e512Google Scholar
  4. Ampuero J, Simon M, Montoliu C et al (2015) Minimal hepatic encephalopathy and critical flicker frequency are associated with survival of patients with cirrhosis. Gastroenterology 149:1483–1489CrossRefGoogle Scholar
  5. Bajaj JS, Saeian K, Schubert CM, Hafeezullah M, Franco J, Varma RR, Gibson DP, Hoffmann RG, Stravitz RT, Heuman DM, Sterling RK, Shiffman M, Topaz A, Boyett S, Bell D, Sanyal AJ (2009) Minimal hepatic encephalopathy is associated with motor vehicle crashes: the reality beyond the driving test. Hepatology 50:1175–1183CrossRefGoogle Scholar
  6. Bajaj JS, O'Leary JG, Tandon P, et al (2017) Hepatic Encephalopathy Is Associated With Mortality in Patients With Cirrhosis Independent of Other Extrahepatic Organ Failures. Clin Gastroenterol Hepatol 15(4):565–574.e4Google Scholar
  7. Duarte-Rojo A, Estradas J, Hernandez-Ramos R et al (2011) Validation of the psychometric hepatic encephalopathy score (PHES) for identifying patients with minimal hepatic encephalopathy. Dig Dis Sci 56:3014–3023CrossRefGoogle Scholar
  8. Gupta D, Ingle M, Shah K, Phadke A, Sawant P (2015) Prospective comparative study of inhibitory control test and psychometric hepatic encephalopathy score for diagnosis and prognosis of minimal hepatic encephalopathy in cirrhotic patients in the Indian subcontinent. J Dig Dis 16:400–407CrossRefGoogle Scholar
  9. Lauridsen MM, Schaffalitzky de Muckadell OB, Vilstrup H (2015) Minimal hepatic encephalopathy characterized by parallel use of the continuous reaction time and portosystemic encephalopathy tests. Metab Brain Dis 30:1187–1192CrossRefGoogle Scholar
  10. Montagnese S, Balistreri E, Schiff S, de Rui M, Angeli P, Zanus G, Cillo U, Bombonato G, Bolognesi M, Sacerdoti D, Gatta A, Merkel C, Amodio P (2014) Covert hepatic encephalopathy: agreement and predictive validity of different indices. World J Gastroenterol 20:15756–15762CrossRefGoogle Scholar
  11. Ortiz M, Cordoba J, Jacas C et al (2006) Neuropsychological abnormalities in cirrhosis include learning impairment. J Hepatol 44:104–110CrossRefGoogle Scholar
  12. Patidar KR, Bajaj JS (2015) Covert and overt hepatic encephalopathy: diagnosis and management. Clin Gastroenterol Hepatol 13:2048–2061CrossRefGoogle Scholar
  13. Prasad S, Dhiman RK, Duseja A, Chawla YK, Sharma A, Agarwal R (2007) Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy. Hepatology 45:549–559CrossRefGoogle Scholar
  14. Rai R, Ahuja CK, Agrawal S, Kalra N, Duseja A, Khandelwal N, Chawla Y, Dhiman RK (2015) Reversal of low-grade cerebral edema after lactulose/Rifaximin therapy in patients with cirrhosis and minimal hepatic encephalopathy. Clin Transl Gastroenterol 6:e111CrossRefGoogle Scholar
  15. Riggio O, Amodio P, Farcomeni A, Merli M, Nardelli S, Pasquale C, Pentassuglio I, Gioia S, Onori E, Piazza N, de Rui M, Schiff S, Montagnese S (2015) A model for predicting development of overt hepatic encephalopathy in patients with cirrhosis. Clin Gastroenterol Hepatol 13:1346–1352CrossRefGoogle Scholar
  16. Romero Gomez M, Cordoba J, Jover R et al (2006) Normality tables in the Spanish population for psychometric tests used in the diagnosis of minimal hepatic encephalopathy. Med Clin (Barc) 127:246–249CrossRefGoogle Scholar
  17. Soriano G, Roman E, Cordoba J et al (2012) Cognitive dysfunction in cirrhosis is associated with falls: a prospective study. Hepatology 55:1922–1930CrossRefGoogle Scholar
  18. Thomsen KL, Macnaughtan J, Tritto G, Mookerjee RP, Jalan R (2016) Clinical and pathophysiological characteristics of cirrhotic patients with grade 1 and minimal hepatic encephalopathy. PLoS One 11:e0146076CrossRefGoogle Scholar
  19. Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, Weissenborn K, Wong P (2014) Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the liver. Hepatology 60:715–735CrossRefGoogle Scholar
  20. Volk ML, Tocco RS, Bazick J, Rakoski MO, Lok AS (2012) Hospital readmissions among patients with decompensated cirrhosis. Am J Gastroenterol 107:247–252CrossRefGoogle Scholar
  21. Wein C, Koch H, Popp B, Oehler G, Schauder P (2004) Minimal hepatic encephalopathy impairs fitness to drive. Hepatology 39:739–745CrossRefGoogle Scholar
  22. Weissenborn K (2015) The clinical relevance of minimal hepatic encephalopathy--a critical look. Dig Dis 33:555–561CrossRefGoogle Scholar
  23. Weissenborn K, Ennen JC, Schomerus H, Rückert N, Hecker H (2001) Neuropsychological characterization of hepatic encephalopathy. J Hepatol 34:768–773CrossRefGoogle Scholar

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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