Metabolic Brain Disease

, Volume 30, Issue 5, pp 1187–1192 | Cite as

Minimal hepatic encephalopathy characterized by parallel use of the continuous reaction time and portosystemic encephalopathy tests

  • M. M. Lauridsen
  • O. B. Schaffalitzky de Muckadell
  • H. Vilstrup
Research Article


Minimal hepatic encephalopathy (MHE) is a frequent complication to liver cirrhosis that causes poor quality of life, a great burden to caregivers, and can be treated. For diagnosis and grading the international guidelines recommend the use of psychometric tests of different modalities (computer based vs. paper and pencil). To compare results of the Continuous Reaction time (CRT) and the Portosystemic Encephalopathy (PSE) tests in a large unselected cohort of cirrhosis patients without clinically detectable brain impairment and to clinically characterize the patients according to their test results. The CRT method is a 10–minute computerized test of a patient’s motor reaction time stability (CRTindex) to 150 auditory stimuli. The PSE test is a 20–minute paper-pencil test evaluating psychomotor speed. Both tests were performed at the same occasion in 129 patients. Both tests were normal in only 36 % (n = 46) of the patients and this group had the best quality of life, a normal CRP, a low risk of subsequent overt HE, and a low short term mortality. Either the CRT or the PSE test was abnormal in a total of 64 % of the patients (n = 83), the CRT in 53 % (n = 69) and the PSE in 34 % (n = 44). All these patients had a poorer quality of life, low-grade CRP elevation, moderate risk for subsequent overt HE, and a higher than 20 % short term mortality. Both tests were abnormal in 23 % (n = 30) of the patients and this group had more advanced cirrhosis and a 40 % short-term mortality. One of the tests was abnormal in the majority of the patients but concordant in only 60 %. Most cirrhosis patients seem to have impairments of different cognitive domains and more domains with advancing disease. Two abnormal tests identified patients with an increased risk of overt HE and death.


Hepatic encephalopathy Reaction time Psychometric test Portosystemic encephalopathy test Liver cirrhosis 


  1. Arguedas MR, DeLawrence TG, McGuire BM (2003) Influence of hepatic encephalopathy on health-related quality of life in patients with cirrhosis. Dig Dis Sci 48(8):1622–1626CrossRefPubMedGoogle Scholar
  2. Bajaj JS (2008) Minimal hepatic encephalopathy matters in daily life. World J Gastroenterol 14(23):3609–3615PubMedCentralCrossRefPubMedGoogle Scholar
  3. Bajaj JS, Saeian K, Schubert CM, Hafeezullah M, Franco J, Varma RR et al (2009) Minimal hepatic encephalopathy is associated with motor vehicle crashes: the reality beyond the driving test. Hepatology 50(4):1175–1183PubMedCentralCrossRefPubMedGoogle Scholar
  4. Bajaj JS, Wade JB, Gibson DP, Heuman DM, Thacker LR, Sterling RK et al (2011a) The multi-dimensional burden of cirrhosis and hepatic encephalopathy on patients and caregivers. Am J Gastroenterol 106(9):1646–1653PubMedCentralCrossRefPubMedGoogle Scholar
  5. Bajaj JS, Heuman DM, Wade JB, Gibson DP, Saeian K, Wegelin JA et al (2011b) Rifaximin improves driving simulator performance in a randomized trial of patients with minimal hepatic encephalopathy. Gastroenterology 140(2):478–87.e1PubMedCentralCrossRefPubMedGoogle Scholar
  6. Bajaj JS, Heuman DM, Sterling RK, Sanyal AJ, Siddiqui M, Matherly S et al (2014) Validation of EncephalApp, smartphone-based stroop test, for the diagnosis of covert hepatic encephalopathy. Clin Gastroenterol HepatolGoogle Scholar
  7. Elsass P (1986) Continuous reaction times in cerebral dysfunction. Acta Neurol Scand 73:225–246CrossRefPubMedGoogle Scholar
  8. Elsass P, Christensen SE, Mortensen EL, Vilstrup H (1985) Discrimination between organic and hepatic encephalopathy by means of continuous reaction times. Liver 5(1):29–34CrossRefPubMedGoogle Scholar
  9. Goldbecker A, Weissenborn K, Hamidi Shahrezaei G, Afshar K, Rumke S, Barg-Hock H et al (2013) Comparison of the most favoured methods for the diagnosis of hepatic encephalopathy in liver transplantation candidates. Gut 62(10):1497–1504CrossRefPubMedGoogle Scholar
  10. Groeneweg M, Quero JC, De Bruijn I, Hartmann IJ, Essink-bot ML, Hop WC et al (1998) Subclinical hepatic encephalopathy impairs daily functioning. Hepatology 28(1):45–49CrossRefPubMedGoogle Scholar
  11. Jakobsen LH, Sorensen JM, Rask IK, Jensen BS, Kondrup J (2010) Validation of reaction time as a measure of cognitive function and quality of life in healthy subjects and patients. NutritionGoogle Scholar
  12. Jepsen P, Vilstrup H, Andersen PK, Lash TL, Sorensen HT (2008) Comorbidity and survival of Danish cirrhosis patients: a nationwide population-based cohort study. Hepatology 48(1):214–220CrossRefPubMedGoogle Scholar
  13. Kato A, Kato M, Ishii H, Ichimiya Y, Suzuki K, Kawasaki H et al (2004) Development of quantitative neuropsychological tests for diagnosis of subclinical hepatic encephalopathy in liver cirrhosis patients and establishment of diagnostic criteria-multicenter collaborative study in Japanese. Hepatol Res Off J Jpn Soc Hepatol 30(2):71–78CrossRefGoogle Scholar
  14. Lauridsen MM, Jepsen P, Vilstrup H (2011) Critical flicker frequency and continuous reaction times for the diagnosis of minimal hepatic encephalopathy: a comparative study of 154 patients with liver disease. Metab Brain Dis 26(2):135–139CrossRefPubMedGoogle Scholar
  15. Lauridsen MM, Gronbaek H, Naeser EB, Leth ST, Vilstrup H (2012) Gender and age effects on the continuous reaction times method in volunteers and patients with cirrhosis. Metab Brain DisGoogle Scholar
  16. Lauridsen MM, Thiele M, Kimer N, Vilstrup H (2013) The continuous reaction times method for diagnosing, grading, and monitoring minimal/covert hepatic encephalopathy. Metab Brain DisGoogle Scholar
  17. Lauridsen MM, Frojk J, de Muckadell OB, Vilstrup H (2014) Opposite effects of sleep deprivation on the continuous reaction times in patients with liver cirrhosis and normal persons. Metab Brain Dis 29(3):655–660CrossRefPubMedGoogle Scholar
  18. Li SW, Wang K, Yu YQ, Wang HB, Li YH, Xu JM (2013) Psychometric hepatic encephalopathy score for diagnosis of minimal hepatic encephalopathy in China. World J Gastroenterol 19(46):8745–8751PubMedCentralCrossRefPubMedGoogle Scholar
  19. Maldonado-Garza HJ, Vazquez-Elizondo G, Gaytan-Torres JO, Flores-Rendon AR, Cardenas-Sandoval MG, Bosques-Padilla FJ (2011) Prevalence of minimal hepatic encephalopathy in cirrhotic patients. Ann Hepatol 10(Suppl 2):S40–S44PubMedGoogle Scholar
  20. Montagnese S, Biancardi A, Schiff S, Carraro P, Carla V, Mannaioni G et al (2011) Different biochemical correlates for different neuropsychiatric abnormalities in patients with cirrhosis. Hepatology 53(2):558–566CrossRefPubMedGoogle Scholar
  21. Nabi E, Thacker LR, Wade JB, Sterling RK, Stravitz RT, Fuchs M et al (2014) Diagnosis of covert hepatic encephalopathy without specialized tests. Clin Gastroenterol Hepatol 12(8):384–9.e2CrossRefGoogle Scholar
  22. Ortiz M, Jacas C, Cordoba J (2005) Minimal hepatic encephalopathy: diagnosis, clinical significance and recommendations. J Hepatol 42(Suppl 1):S45–S53CrossRefPubMedGoogle Scholar
  23. Patidar KR, Thacker LR, Wade JB, Sterling RK, Sanyal AJ, Siddiqui MS et al (2014) Covert hepatic encephalopathy is independently associated with poor survival and increased risk of hospitalization. Am J GastroenterolGoogle Scholar
  24. 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(3):549–559CrossRefPubMedGoogle Scholar
  25. Schomerus H, Hamster W (2001) Quality of life in cirrhotics with minimal hepatic encephalopathy. Metab Brain Dis 16(1–2):37–41CrossRefPubMedGoogle Scholar
  26. Sharma P, Sharma BC, Sarin SK (2010) Critical flicker frequency for diagnosis and assessment of recovery from minimal hepatic encephalopathy in patients with cirrhosis. Hepatobiliary Pancreat Dis Int 9(1):27–32PubMedGoogle Scholar
  27. Shawcross DL, Davies NA, Williams R, Jalan R (2004) Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J Hepatol 40(2):247–254CrossRefPubMedGoogle Scholar
  28. Sidhu SS, Goyal O, Mishra BP, Sood A, Chhina RS, Soni RK (2011) Rifaximin improves psychometric performance and health-related quality of life in patients with minimal hepatic encephalopathy (the RIME Trial). Am J Gastroenterol 106(2):307–316CrossRefPubMedGoogle Scholar
  29. Sturgeon JP, Shawcross DL (2014) Recent insights into the pathogenesis of hepatic encephalopathy and treatments. Exp Rev Gastroenterol Hepatol 8(1):83–100CrossRefGoogle Scholar
  30. Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD et al (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(2):715–735CrossRefPubMedGoogle Scholar
  31. Weissenborn K (2012) Psychometric tests for diagnosing minimal hepatic encephalopathy. Metab Brain DisGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • M. M. Lauridsen
    • 1
    • 2
  • O. B. Schaffalitzky de Muckadell
    • 2
  • H. Vilstrup
    • 3
  1. 1.Department of GastroenterologyHospital of South West JutlandEsbjergDenmark
  2. 2.Department of GastroenterologyOdense University HospitalOdense CDenmark
  3. 3.Department of Hepatology and GastroenterologyAarhus University HospitalAarhusDenmark

Personalised recommendations