How to diagnose hepatic encephalopathy?

Diagnosing Hepatic Encephalopathy

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

Clinical Evaluation

• HE should be classified according to the type of underlying disease, severity of manifestations, time course, and precipitating factors 1
• Clinical examination remains the cornerstone for diagnosing overt HE (OHE), using standardized scales:
  • West Haven Criteria (WHC) for grading severity (grades 0-4) 1
  • Glasgow Coma Scale (GCS) for patients with significantly altered consciousness 1
• Key clinical signs to assess:
  • Orientation status and presence of asterixis (have good inter-rater reliability) 1
  • Recent medical history (infections, trauma, withdrawal, psychotropic drugs) 1
  • Complete medical history (diabetes, neurovascular diseases, epilepsy, complications of cirrhosis) 1
  • Neurological examination including cognitive, motor, sensory, neurovisual and cranial nerve testing 1

Laboratory Testing

• Blood ammonia measurement:
  • A normal ammonia level in a patient with suspected OHE calls for diagnostic reevaluation 1
  • However, elevated ammonia alone does not confirm HE diagnosis (may be elevated without symptoms) 1
  • Proper collection technique is crucial for accurate results:
    • Fasting patient
    • Avoid venous stasis (tourniquet, fist clenching)
    • Collect in EDTA tube and place immediately on ice
    • Transport to lab at 4°C within 60-90 minutes 1
• Common blood tests required:
  • Blood electrolytes, glucose, calcium
  • Complete blood count, haemostasis
  • Inflammatory markers
  • Renal function (blood urea, creatinine) 1

Imaging Studies

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

Testing for Covert HE (Minimal HE and Grade 1 HE)

• Covert HE requires specialized testing as it's not obvious on routine clinical examination 1, 2
• For multicenter studies or research, at least two validated testing strategies should be used:
  • Paper-pencil tests (Psychometric Hepatic Encephalopathy Score - PHES) and
  • Either computerized tests (Critical Flicker Frequency, reaction time) or
  • Neurophysiological tests (EEG, evoked potentials) 1
• Animal Naming Test is a simple screening tool:
  • Ask patient to list as many animal names as possible in 1 minute
  • Cut-off of 20 animal names (below this threshold suggests covert HE) 1

Differential Diagnosis

• Common differential diagnoses to exclude:
  • Metabolic encephalopathy (uremia, hypercapnia, hypoglycemia)
  • Hydroelectrolytic disorders (hypokalaemia, hypomagnesaemia)
  • Drug-induced conditions (antiepileptics, levodopa, opiates, benzodiazepines)
  • Focal brain lesions
  • Wernicke-Korsakoff syndrome (especially in alcoholic patients)
  • Cerebral microangiopathy
  • Neurodegenerative diseases
  • Psychiatric disorders 1, 3

Clinical Pitfalls and Caveats

• Grade 1 HE can be easily overlooked as slight hypokinesia, psychomotor slowing, and lack of attention may not be obvious on clinical examination 1
• Cognitive complaints may not always correlate with actual cognitive impairment - some patients report symptoms without objective findings 1
• Ammonia measurement is technically challenging and requires strict adherence to collection protocols to avoid false results 1
• In patients with multiple comorbidities or low educational background, neurophysiological tests may be more useful than psychometric tests 1
• Always consider the possibility of intracerebral hemorrhage in cirrhotic patients with new neurological symptoms 1

By systematically applying these diagnostic approaches, clinicians can accurately identify hepatic encephalopathy and distinguish it from other causes of altered mental status in patients with liver disease.