Diagnosing Hepatic Encephalopathy

Clinical Evaluation

The European Association for the Study of the Liver recommends that hepatic encephalopathy (HE) should be diagnosed through exclusion of other causes of brain dysfunction, with a systematic clinical and paraclinical work-up that includes blood tests and brain imaging, preferably MRI 1, 2
HE should be classified according to the type of underlying disease, severity of manifestations, time course, and precipitating factors 3
Clinical examination remains the cornerstone for diagnosing overt HE (OHE), using standardized scales such as the West Haven Criteria (WHC) for grading severity (grades 0-4) 1, 3
The Glasgow Coma Scale (GCS) should be used for patients with significantly altered consciousness 3
Key clinical signs to assess include orientation status, presence of asterixis, recent medical history, complete medical history, and neurological examination including cognitive, motor, sensory, neurovisual and cranial nerve testing 2, 3

Blood ammonia measurement is crucial, but a normal ammonia level in a patient with suspected OHE calls for diagnostic reevaluation 1, 4
Elevated ammonia alone does not confirm HE diagnosis, and proper collection technique is essential for accurate results, including fasting patient, avoiding venous stasis, and collecting in EDTA tube and placing immediately on ice 2, 5, 6
Common blood tests required include blood electrolytes, glucose, calcium, complete blood count, haemostasis, inflammatory markers, and renal function (blood urea, creatinine) 1, 2

Brain imaging (preferably MRI) is essential for differential diagnosis, especially during the first episode of HE 5
CT or MRI scans do not contribute to HE diagnosis or grading but are important to exclude other pathologies, and cirrhotic patients have at least a 5-fold increased risk of intracerebral hemorrhage 1, 4

Covert HE requires specialized testing, and for multicenter studies or research, at least two validated testing strategies should be used, including paper-pencil tests (Psychometric Hepatic Encephalopathy Score - PHES) and computerized tests (Critical Flicker Frequency, reaction time) or neurophysiological tests (EEG, evoked potentials) 1, 4, 7
The Animal Naming Test is a simple screening tool, where patients are asked to list as many animal names as possible in 1 minute, and a cut-off of 20 animal names suggests covert HE 5

Common differential diagnoses to exclude include hydroelectrolytic disorders, drug-induced conditions, focal brain lesions, Wernicke-Korsakoff syndrome, cerebral microangiopathy, neurodegenerative diseases, and psychiatric disorders 1, 2, 6

Evaluate for specific cognitive deficits in attention, visuospatial abilities, fine motor skills, and memory, which are commonly impaired in hepatic encephalopathy, as recommended by the American Association for the Study of Liver Diseases 8

Consider electroencephalogram (EEG) or evoked potentials for objective assessment of brain function, particularly in patients with covert hepatic encephalopathy, according to the European Association for the Study of the Liver 9

Use validated neuropsychological test batteries that measure multiple cognitive domains, such as the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) or PSE-Syndrom-Test, which have met psychometric and clinical validity criteria for assessing minimal hepatic encephalopathy, as suggested by the American Association for the Study of Liver Diseases 10, 11
Implement either the RBANS or PSE-Syndrom-Test to assess minimal hepatic encephalopathy, as recommended by the European Association for the Study of the Liver 10, 11

Be aware that minimal/covert hepatic encephalopathy significantly impacts quality of life, predicts development of overt encephalopathy, and may be associated with poorer prognosis, according to the American Association for the Study of Liver Diseases 12

The European Association for the Study of the Liver recommends using either RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) or PSE-Syndrom-Test as validated batteries for diagnosing covert hepatic encephalopathy, which measure multiple cognitive domains and have met psychometric and clinical validity criteria 13
Neuropsychological test batteries measuring multiple cognitive domains are more reliable than single tests and correlate more strongly with functional status, according to the Liver International guideline 13

The use of RBANS versus PSE-Syndrom-Test should be based on availability of local translations and normative data, as suggested by the Liver International guideline 13