How do you differentiate between delirium and hepatic encephalopathy in patients presenting with altered mental status?

Differentiating Delirium from Hepatic Encephalopathy

Hepatic encephalopathy IS a form of delirium—specifically, delirium caused by liver dysfunction—making differentiation about identifying HE as the cause versus other etiologies of delirium in patients with liver disease. 1

Key Conceptual Framework

The critical distinction is not "delirium versus HE" but rather determining whether altered mental status in a patient with liver disease is:

• Hepatic encephalopathy (delirium caused by hepatic dysfunction/portosystemic shunting)
• Delirium from other causes (infection, medications, metabolic derangements, structural brain lesions)
• Both simultaneously (HE with superimposed alternative causes)

HE remains a diagnosis of exclusion even in patients with known liver disease. 1

Diagnostic Algorithm

Step 1: Measure Plasma Ammonia

A normal ammonia level essentially rules out HE as the primary cause. 1

• If ammonia is normal in a patient with cirrhosis and delirium, aggressively pursue alternative diagnoses 1
• Elevated ammonia supports but does not confirm HE, as hyperammonemia can occur without manifest HE 1
• Ammonia correlates with HE severity but may remain elevated after clinical resolution 1

Step 2: Identify Alternative/Concomitant Causes

In 22% of patients with liver disease suspected of having HE, extrahepatic causes were identified as the actual etiology. 1

Required investigations include: 1, 2

• Infections: Urinary tract infection, pneumonia, spontaneous bacterial peritonitis
• Metabolic: Glucose, electrolytes (especially hyponatremia), renal function, thyroid function
• Hematologic: Complete blood count, inflammatory markers (CRP)
• Toxicologic: Blood alcohol level, psychoactive drug screening
• Neurologic: Brain imaging (CT/MRI) for stroke, subdural hematoma, intracranial bleeding 1
• Seizure activity: EEG to exclude nonconvulsive status epilepticus 1, 3
• Infectious: Lumbar puncture if meningitis/encephalitis suspected 1

Step 3: Assess for HE-Specific Features

Marker symptoms with good inter-rater reliability: 1

• Disorientation (particularly to time) - distinguishes Grade II HE from lower grades 1
• Asterixis (flapping tremor) - specific for HE when present 1, 4

Clinical grading using West Haven Criteria (for Grade ≥2): 1

• Grade II: Lethargy, disorientation to time
• Grade III: Somnolence, disorientation to place, marked confusion
• Grade IV: Coma

For severe impairment, add Glasgow Coma Scale assessment. 1

Step 4: Look for HE Precipitants

If HE is suspected, identify triggering factors: 2

• Gastrointestinal bleeding
• Infection
• Constipation
• Dehydration
• Acute kidney injury
• Electrolyte disturbances (especially alkalosis)
• Sedative medications (benzodiazepines, opioids)
• Inappropriate lactulose use

Critical Differentiating Features

Features Suggesting HE Rather Than Other Delirium:

• Known cirrhosis with portal hypertension or portosystemic shunts 1
• Elevated ammonia level 1
• Asterixis present 1, 4
• Identifiable HE precipitant 2
• Improvement with lactulose therapy 1

Features Suggesting Alternative Diagnosis:

• Normal ammonia level - most important red flag 1
• Focal neurological signs (suggests structural lesion) 1
• Fever with nuchal rigidity (suggests meningitis) 1
• Seizure activity on EEG 3
• No improvement with standard HE therapy 1
• Acute onset in patient without known liver disease 1

Common Pitfalls

Do not assume altered mental status equals HE in cirrhotic patients. Studies show that up to 22% have alternative causes. 1

Grade I HE has poor inter-rater reliability and overlaps significantly with early delirium from other causes—both present with subtle psychomotor slowing and inattention. 1

Covert HE (minimal HE + Grade I) overlaps with mild cognitive impairment in elderly patients, but MCI develops over ≥6 months while HE fluctuates more acutely. 1

Poor response to HE treatment mandates reassessment for alternative diagnoses, not simply escalation of HE therapy. 1

Nonconvulsive status epilepticus can mimic HE and requires EEG for diagnosis, especially when mental status remains altered despite optimal HE management. 3