How should hepatic encephalopathy be evaluated in a patient with known or suspected liver disease presenting with altered mental status or subtle cognitive changes?

How to Test for Hepatic Encephalopathy

The diagnosis of overt hepatic encephalopathy (OHE) is made clinically using the West Haven Criteria and assessment for disorientation and asterixis, while covert hepatic encephalopathy (CHE) requires at least two validated psychometric or neurophysiological tests. 1

Initial Clinical Assessment for Overt HE

Begin by applying the West Haven Criteria as your gold standard for grading severity (Grade 0 = normal to Grade 4 = coma), specifically looking for disorientation to time/place/person and asterixis, which have the best inter-rater reliability as marker symptoms. 1, 2

For patients with significantly altered consciousness, use the Glasgow Coma Scale to provide an objective, operative assessment of eye opening, verbal response, and motor response. 1

Critical Caveat: HE Remains a Diagnosis of Exclusion

Even in patients with known cirrhosis, you must systematically exclude other causes of altered mental status before attributing symptoms to HE. 1, 2 This population is particularly susceptible to multiple simultaneous etiologies including:

• Medication effects (benzodiazepines, sedatives) 3
• Metabolic derangements (hyponatremia, electrolyte disturbances) 1, 3
• Infections (septic encephalopathy, spontaneous bacterial peritonitis) 3
• Intracranial pathology (hemorrhage, stroke—cirrhotic patients have 5-fold increased risk of intracerebral hemorrhage) 4, 3
• Alcohol intoxication or withdrawal 1
• Gastrointestinal bleeding 3

Essential Diagnostic Workup

Mandatory Laboratory Tests

Obtain the following blood tests for every patient with suspected HE: 2, 4

• Ammonia level (fasting, avoid venous stasis, collect in EDTA tube on ice immediately) 4
• Complete metabolic panel (electrolytes, glucose, calcium, renal function) 2, 4
• Complete blood count 4
• Inflammatory markers 4

A normal ammonia level essentially rules out HE as the primary cause and should prompt aggressive pursuit of alternative diagnoses. 2 However, elevated ammonia alone does not confirm HE, as hyperammonemia can occur without manifest encephalopathy and may remain elevated after clinical resolution. 2

Imaging Requirements

Brain imaging (preferably MRI) is essential for the first episode of HE to exclude structural lesions, hemorrhage, and other pathologies. 2, 4 For recurrent episodes in patients with known HE, imaging is not routinely required unless new focal signs develop. 2

Consider EEG when the diagnosis is uncertain or to provide objective assessment of brain function. 2, 4

Testing for Covert/Minimal Hepatic Encephalopathy

Use at least two validated tests from different modalities to diagnose covert HE, as no single test captures all affected cognitive domains. 1, 2

Recommended Test Combinations

Paper-pencil psychometric tests: 2, 4

• Psychometric Hepatic Encephalopathy Score (PHES)—measures multiple cognitive domains
• Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) 4
• PSE-Syndrom-Test 4

Computerized tests: 4

• Critical Flicker Frequency (CFF)
• Reaction time tests

Neurophysiological tests: 4

• EEG
• Evoked potentials

Simple Screening Tool

The Animal Naming Test provides quick screening: ask the patient to name as many animals as possible in 1 minute; fewer than 20 animals suggests covert HE. 4

Practical Testing Algorithm

For Initial Presentation with Altered Mental Status:

1. Clinical examination using West Haven Criteria, assess for disorientation and asterixis 1
2. Blood tests (ammonia, metabolic panel, CBC, inflammatory markers) 2, 4
3. Brain MRI 2, 4
4. Paracentesis if ascites present 2
5. EEG if diagnosis uncertain 2

For Recurrent Episodes in Known HE:

1. Clinical examination 2
2. Blood tests only 2
3. Identify precipitating factors 2
4. Resume/intensify HE therapy 2

For Suspected Covert HE:

1. At least two validated tests (e.g., PHES + CFF) with local normative data 2, 4
2. Consider testing patients with quality of life complaints, complaints from relatives, or before stopping HE therapy 1

Important Pitfalls to Avoid

Do not assume altered mental status is HE without excluding other causes, even in patients with known cirrhosis—in 22% of suspected cases, extrahepatic causes were the actual etiology. 2

Do not rely solely on ammonia levels for diagnosis or severity grading, as they lack specificity and do not add independent diagnostic value beyond clinical assessment. 2, 4

Testing for covert HE should only be performed in patients without confounding conditions (active substance abuse, psychiatric disorders, other neurological diseases) that would invalidate test results. 1