The continuous reaction time test for minimal hepatic encephalopathy validated by a randomized controlled multi-modal intervention-A pilot study

• Published in: PloS one Vol. 12; no. 10; p. e0185412
• Main Authors: Lauridsen, M M, Mikkelsen, S, Svensson, T, Holm, J, Klüver, C, Gram, J, Vilstrup, H, Schaffalitzky de Muckadell, O B
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.10.2017; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Alcohol; Alertness; Amino acids; Analysis; Biology and Life Sciences; Care and treatment; Chain branching; Change detection; Cirrhosis; Cognition; Diagnosis; Encephalopathy; Engineering and Technology; Female; Gastroenterology; Gastrointestinal diseases; Hepatic encephalopathy; Hepatic Encephalopathy - diagnosis; Hepatic Encephalopathy - pathology; Hepatology; Hospitals; Humans; Intervention; Lactulose; Liver; Liver cirrhosis; Liver diseases; Liver encephalopathy; Male; Medicine and Health Sciences; Middle Aged; Patient Dropouts; Patients; Personal computers; Physical Sciences; Pilot Projects; Placebos; Psychometrics; Quality of life; Quantitative psychology; Randomization; Reaction time; Reproducibility; Reproducibility of Results; Research and Analysis Methods; Social Sciences; Time Factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0185412

Minimal hepatic encephalopathy (MHE) is clinically undetectable and the diagnosis requires psychometric tests. However, a lack of clarity exists as to whether the tests are in fact able to detect changes in cognition. To examine if the continuous reaction time test (CRT) can detect changes in cognition with anti-HE intervention in patients with cirrhosis and without clinically manifest hepatic encephalopathy (HE). Firstly, we conducted a reproducibility analysis and secondly measured change in CRT induced by anti-HE treatment in a randomized controlled pilot study: We stratified 44 patients with liver cirrhosis and without clinically manifest HE according to a normal (n = 22) or abnormal (n = 22) CRT. Each stratum was then block randomized to receive multimodal anti-HE intervention (lactulose+branched-chain amino acids+rifaximin) or triple placebos for 3 months in a double-blinded fashion. The CRT is a simple PC-based test and the test result, the CRT index (normal threshold > 1.9), describes the patient's stability of alertness during the 10-minute test. Our study outcome was the change in CRT index in each group at study exit. The portosystemic encephalopathy (PSE) test, a paper-and-pencil test battery (normal threshold above -5), was used as a comparator test according to international guidelines. The patients with an abnormal CRT index who were randomized to receive the active intervention normalized or improved their CRT index (mean change 0.92 ± 0.29, p = 0.01). Additionally, their PSE improved (change 3.85 ± 1.83, p = 0.03). There was no such effect in any of the other study groups. In this cohort of patients with liver cirrhosis and no manifest HE, the CRT identified a group in whom cognition improved with intensive anti-HE intervention. This finding infers that the CRT can detect a response to treatment and might help in selecting patients for treatment.