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Metab Brain Dis. 2016 Dec;31(6):1217-1229. Epub 2015 Sep 28.

Qualifying and quantifying minimal hepatic encephalopathy.

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UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, Rowland Hill Street, London, NW32PF, UK.
Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
Department of Medicine, St Mary's Hospital Campus, Imperial College, London, W2 1NY, UK.
Department of Neurophysiology, Royal Free Hospital, Royal Free London NHS Foundation Trust, Pond Street, London, Hampstead, NW3 2QG, UK.
Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Department of Gastroenterology, Hospital of South West Jutland, Finsensgade 35, 6700, Esbjerg, Denmark.
Department of Neurology, Hannover Medical School, 30623, Hannover, Germany.


Minimal hepatic encephalopathy is the term applied to the neuropsychiatric status of patients with cirrhosis who are unimpaired on clinical examination but show alterations in neuropsychological tests exploring psychomotor speed/executive function and/or in neurophysiological variables. There is no gold standard for the diagnosis of this syndrome. As these patients have, by definition, no recognizable clinical features of brain dysfunction, the primary prerequisite for the diagnosis is careful exclusion of clinical symptoms and signs. A large number of psychometric tests/test systems have been evaluated in this patient group. Of these the best known and validated is the Portal Systemic Hepatic Encephalopathy Score (PHES) derived from a test battery of five paper and pencil tests; normative reference data are available in several countries. The electroencephalogram (EEG) has been used to diagnose hepatic encephalopathy since the 1950s but, once popular, the technology is not as accessible now as it once was. The performance characteristics of the EEG are critically dependent on the type of analysis undertaken; spectral analysis has better performance characteristics than visual analysis; evolving analytical techniques may provide better diagnostic information while the advent of portable wireless headsets may facilitate more widespread use. A large number of other diagnostic tools have been validated for the diagnosis of minimal hepatic encephalopathy including Critical Flicker Frequency, the Inhibitory Control Test, the Stroop test, the Scan package and the Continuous Reaction Time; each has its pros and cons; strengths and weaknesses; protagonists and detractors. Recent AASLD/EASL Practice Guidelines suggest that the diagnosis of minimal hepatic encephalopathy should be based on the PHES test together with one of the validated alternative techniques or the EEG. Minimal hepatic encephalopathy has a detrimental effect on the well-being of patients and their care-givers. It responds well to treatment with resolution of test abnormalities and the associated detrimental effects on quality of life, liver-related mortality and morbidity. Patients will only benefit in this way if they can be effectively diagnosed. Corporate efforts and consensus agreements are needed to develop effective diagnostic algorithms.


Diagnosis; Minimal hepatic encephalopathy; Neurophysiology; Neuropsychometry

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