What is the evidence-based approach to diagnosing and treating a patient with suspected hepatic encephalopathy and a history of liver disease?

Evidence-Based Diagnosis of Hepatic Encephalopathy

Immediate Diagnostic Approach

Hepatic encephalopathy remains a diagnosis of exclusion requiring systematic evaluation to rule out alternative causes of altered mental status, combined with clinical assessment using standardized grading scales and selective laboratory/imaging studies. 1, 2

The diagnostic workup must proceed along four parallel tracks: clinical grading, exclusion of mimics, identification of precipitants, and confirmatory testing 3, 2.

Clinical Assessment and Grading

For Overt Hepatic Encephalopathy (Grades 2-4)

• Use the West Haven Criteria as the primary grading tool when temporal disorientation is present (disorientation to day, week, month, season, or year indicates at least Grade 2) 1.
• Key clinical signs with good inter-rater reliability include disorientation and asterixis—these are the marker symptoms of overt HE 1.
• Add the Glasgow Coma Scale for patients with Grade 3-4 encephalopathy or significantly altered consciousness to provide objective, reproducible assessment 1, 3.

For Covert/Minimal Hepatic Encephalopathy (Grade 0-1)

• Clinical examination alone is insufficient—specialized testing is required 1, 2.
• The Animal Naming Test serves as a simple bedside screening tool: ask patients to name as many animals as possible in 60 seconds; fewer than 20 animals suggests covert HE 2.
• For definitive diagnosis, use at least two validated testing strategies: paper-pencil tests (Psychometric Hepatic Encephalopathy Score) plus either computerized tests (Critical Flicker Frequency) or neurophysiological tests (EEG) 1, 2.
• The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) or PSE-Syndrom-Test are validated comprehensive batteries measuring multiple cognitive domains 2.

Laboratory Testing

Ammonia Measurement

• Obtain a venous or arterial ammonia level with proper collection technique in all patients with suspected HE 1, 3.
• A normal ammonia level essentially excludes hepatic encephalopathy and mandates immediate reevaluation for alternative diagnoses 1, 2.
• Elevated ammonia alone does not confirm HE diagnosis—it must be interpreted in clinical context 1, 2.

Critical collection technique to avoid false results 2:

• Patient should be fasting
• Avoid venous stasis during blood draw
• Collect in EDTA tube
• Place immediately on ice
• Process rapidly

Additional Laboratory Studies

Obtain the following to exclude alternative causes and identify precipitants 2:

• Complete blood count (infection, bleeding)
• Comprehensive metabolic panel including glucose, electrolytes, calcium, renal function
• Inflammatory markers (infection)
• Coagulation studies (bleeding risk)

Brain Imaging

• Perform CT or MRI during the first episode of altered mental status to exclude intracranial hemorrhage, stroke, or structural lesions 1, 3, 2.
• Cirrhotic patients have at least 5-fold increased risk of intracerebral hemorrhage, making imaging essential 1, 2.
• Brain imaging is also indicated for seizures, focal neurological signs, or failure to respond to treatment 1, 4.
• Imaging does not confirm HE diagnosis or contribute to grading—it serves only to exclude mimics 1, 2.

Systematic Exclusion of Alternative Diagnoses

The following conditions must be actively excluded 1, 2:

Metabolic/Endocrine Causes

• Hypoglycemia, diabetic ketoacidosis, hyperosmolar state 1
• Hyponatremia and hypercalcemia 1
• Uremic encephalopathy (may overlap with HE in end-stage liver disease) 1

Toxic/Medication-Induced

• Alcohol intoxication, withdrawal, or Wernicke encephalopathy 1
• Benzodiazepines, neuroleptics, opioids 1

Neurological Causes

• Intracranial hemorrhage or stroke 1
• Nonconvulsive status epilepticus 1
• Neuroinfections (meningitis, encephalitis) 1

Other Considerations

• Sepsis (can both mimic and precipitate HE) 1
• Primary psychiatric disorders 1
• Neurodegenerative diseases in chronic presentations 2

Identification of Precipitating Factors

Precipitating factors can be identified in nearly all episodes of HE and must be actively sought 1, 3:

• Infections (spontaneous bacterial peritonitis, urinary tract infection, pneumonia) 3
• Gastrointestinal bleeding 3
• Constipation 3
• Dehydration and electrolyte disorders (especially hypokalemia) 3, 4
• Medications (sedatives, diuretics) 3
• Renal dysfunction 4

Classification for Complete Diagnosis

Every case must be classified according to four factors 1:

1. Type of underlying disease: Type A (acute liver failure), Type B (portosystemic bypass without liver disease), Type C (cirrhosis)
2. Severity: Covert (minimal/Grade 1) vs. Overt (Grade 2-4)
3. Time course: Episodic, recurrent (>2 bouts within 6 months), or persistent
4. Precipitating factors: Present or absent (specify if present)

Common Diagnostic Pitfalls

• Grade 1 HE is easily missed on routine clinical examination—slight psychomotor slowing and inattention require specific testing 1.
• Ammonia levels must be collected properly or results are unreliable—improper technique leads to falsely elevated values 2.
• Brain imaging is not diagnostic of HE—do not expect imaging findings to confirm the diagnosis 1, 2.
• Multiple conditions can coexist—sepsis and hyponatremia can both produce encephalopathy independently and precipitate HE simultaneously 1.
• Covert HE significantly impacts quality of life and predicts overt episodes—consider screening high-risk patients even without obvious symptoms 2.