How is hepatic encephalopathy diagnosed in a patient with a history of liver disease, such as cirrhosis, presenting with symptoms like confusion and altered mental status?

Diagnosis of Hepatic Encephalopathy

Hepatic encephalopathy is diagnosed primarily through clinical examination using the West Haven Criteria, combined with exclusion of alternative causes of altered mental status through targeted laboratory and imaging studies. 1

Clinical Diagnosis Framework

Overt Hepatic Encephalopathy (OHE)

The diagnosis of OHE is fundamentally a clinical decision based on bedside examination, not laboratory tests. 1

• Use the West Haven Criteria as the gold standard for grading severity (Grade 1: subtle changes in attention; Grade 2: disorientation to time and asterixis; Grade 3: disorientation to place and marked confusion; Grade 4: coma). 1
• Detection of disorientation and asterixis has good inter-rater reliability and serves as marker symptoms of OHE. 1
• For patients with significantly altered consciousness, apply the Glasgow Coma Scale for operative assessment. 1

Critical pitfall: Grade 1 HE has poor inter-rater reliability because subtle psychomotor slowing and inattention are easily overlooked—rely on disorientation and asterixis for confident diagnosis. 1

Covert Hepatic Encephalopathy (CHE/MHE)

Covert HE requires formal testing because patients lack obvious clinical signs like disorientation or asterixis. 1

• Use at least two validated tests from different modalities: 1
  • Psychometric: Psychometric Hepatic Encephalopathy Score (PHES) is the most widely validated paper-pencil test. 1
  • Computerized: Critical Flicker Frequency (CFF), Continuous Reaction Time (CRT), Inhibitory Control Test (ICT), or Stroop smartphone app. 1, 2
  • Neurophysiological: Quantitative EEG with spectral analysis. 1

Essential Diagnostic Workup

Initial Evaluation for Any Neurological Disorder in Cirrhosis

Every initial presentation of neurological symptoms in a cirrhotic patient requires a comprehensive workup to exclude differential diagnoses—HE remains a diagnosis of exclusion. 1, 3

Mandatory Components:

1. Recent medical history: infections, trauma, medication changes (especially benzodiazepines, opiates, anticholinergics), alcohol withdrawal. 1

2. Complete neurological examination: cognitive testing, motor/sensory function, cranial nerves, asterixis assessment. 1

3. Blood tests (essential for all initial presentations): 1

   • Electrolytes (sodium, potassium, magnesium, calcium)
   • Blood glucose
   • Complete blood count
   • Inflammatory markers
   • Renal function (urea, creatinine)
   • Coagulation studies

4. Brain imaging (preferably MRI) for initial presentations. 1

5. EEG when diagnosis is uncertain. 1

For recurrent OHE episodes in known patients, only blood tests are systematically required—imaging can be omitted. 1

Role of Ammonia Testing

Ammonia measurement is useful but not diagnostic on its own. 1, 4, 3

• A normal ammonia level essentially rules out HE as the primary cause and should prompt aggressive pursuit of alternative diagnoses. 4, 3
• An elevated ammonia level supports but does not confirm HE, as hyperammonemia can occur without encephalopathy. 4, 3
• If checking ammonia, use proper technique: fasting venous sample in EDTA tube, avoid tourniquet/fist clenching, place immediately on ice, transport to lab within 60-90 minutes at +4°C. 1

Critical caveat: The AASLD/EASL guidelines state that high blood ammonia levels alone do not add diagnostic, staging, or prognostic value, but a normal level questions the diagnosis. 1, 4

Diagnostic Paracentesis

In cirrhotic patients with ascites presenting with confusion, perform immediate diagnostic paracentesis to rule out spontaneous bacterial peritonitis (SBP), a common HE precipitant. 5

• Analyze ascitic fluid for: cell count with differential (neutrophils >250/mm³ indicates SBP), culture with bedside inoculation, total protein, and serum-ascites albumin gradient. 5

Key Differential Diagnoses to Exclude

High-Priority Alternatives in Cirrhotic Patients:

Alcohol-related causes (in patients with alcohol use disorder): 1

• Wernicke-Korsakoff syndrome (thiamine deficiency)
• Alcohol withdrawal
• Post-traumatic dementia
• Alcohol-related dementia

Metabolic/toxic causes: 1

• Uremic encephalopathy
• Hypoglycemia
• Severe hyponatremia
• Drug effects (benzodiazepines, opiates, antiepileptics)

Infectious causes: 1

• Spontaneous bacterial peritonitis
• Meningoencephalitis

Structural causes: 1

• Subdural hematoma (common in cirrhosis due to coagulopathy and falls)
• Cerebral microangiopathy
• Focal brain lesions

Clinical Features Suggesting Alternative Diagnosis:

These findings should prompt extensive investigation beyond HE: 1, 3

• Focal neurological signs
• Significant anterograde memory impairment (storage deficits, not just retrieval)
• Visuoconstructive impairments
• Progressive course without fluctuations
• Fever with nuchal rigidity
• No improvement with standard HE therapy (lactulose/rifaximin)

Diagnostic Algorithm Summary

For initial presentation: Clinical examination with West Haven Criteria → Blood tests (electrolytes, glucose, CBC, renal function) → Brain MRI → Paracentesis if ascites present → Consider EEG if uncertain → Trial of HE therapy (lactulose) with response assessment. 1, 5

For recurrent episodes in known HE patients: Clinical examination → Blood tests only → Identify precipitants → Resume/intensify HE therapy. 1

For suspected covert HE: At least two validated tests (PHES plus CFF or computerized test) with local normative data. 1

Critical principle: In 22% of patients with liver disease suspected of having HE, extrahepatic causes were identified as the actual etiology—never assume HE without excluding alternatives. 3