What are the clinical features and management of hepatic encephalopathy?

Clinical Features and Management of Hepatic Encephalopathy

Hepatic encephalopathy (HE) presents with a spectrum of neuropsychiatric abnormalities ranging from subtle cognitive deficits to coma, and management should focus on identifying precipitating factors, administering lactulose as first-line therapy, and considering rifaximin for recurrent episodes. 1, 2, 3

Classification of Hepatic Encephalopathy

HE is classified according to four key factors:

1. Underlying disease:

   • Type A: Resulting from acute liver failure
   • Type B: Resulting from portosystemic bypass/shunting
   • Type C: Resulting from cirrhosis 1

2. Severity of manifestations (West Haven criteria):

   • Covert HE: Minimal to Grade I (no asterixis or disorientation)
   • Overt HE: Grade II-IV (clinically apparent) 1, 2

3. Time course:

   • Episodic HE: Isolated episodes
   • Recurrent HE: Episodes occurring within 6 months
   • Persistent HE: Always present with relapses 1

4. Precipitating factors:

   • Precipitated (most common)
   • Non-precipitated 1

Clinical Features

Neuropsychiatric Manifestations

• Covert HE: Subtle cognitive deficits detectable only by psychometric testing
• Grade I: Mild confusion, shortened attention span, irritability, sleep disturbances
• Grade II: Lethargy, disorientation for time, personality changes, inappropriate behavior
• Grade III: Somnolence, confusion, disorientation for place, bizarre behavior
• Grade IV: Coma, unresponsive to verbal or noxious stimuli 1, 2

Physical Findings

• Asterixis (flapping tremor): Characteristic sign in overt HE
• Fetor hepaticus: Sweet, musty breath odor
• Hyperreflexia and clonus: Common in advanced stages
• Parkinsonian features: May include rigidity, tremor, and shuffling gait (in persistent HE)
• Cerebellar signs: Ataxia, dysarthria, intention tremor 1

Specialized Presentations

• Hepatic myelopathy: Progressive spastic paraparesis with minimal mental changes
• Cirrhosis-associated parkinsonism: Extrapyramidal signs with brain atrophy (occurs in ~4% of advanced cases)
• Cortical blindness: Rare presentation that can precede altered sensorium 1, 4

Diagnostic Approach

Initial Assessment

• Mental status evaluation: Using West Haven criteria and Glasgow Coma Scale
• Blood tests: Ammonia levels, electrolytes, renal function, complete blood count
• Identify precipitating factors: Infections, GI bleeding, electrolyte disorders, constipation, medications 2

Differential Diagnosis

Common conditions to exclude:

• Diabetic complications (hypoglycemia, ketoacidosis)
• Alcohol-related (intoxication, withdrawal, Wernicke's)
• Drug effects (benzodiazepines, opioids)
• Neuroinfections
• Electrolyte disorders (hyponatremia, hypercalcemia)
• Nonconvulsive epilepsy
• Intracranial bleeding and stroke 1

Management

Identify and Treat Precipitating Factors

Common precipitating factors include:

• Gastrointestinal bleeding
• Infections
• Constipation
• Excess dietary protein
• Dehydration
• Electrolyte disturbances (especially hyponatremia)
• Medications (benzodiazepines, opioids)
• Acute liver dysfunction 2

Pharmacological Treatment

1. First-line therapy: Lactulose

   • Initial dose: 25 mL orally every 12 hours
   • Titrate to achieve 2-3 soft bowel movements daily
   • For severe HE: Consider lactulose enema (300 mL lactulose in 700 mL water) 2, 3

2. Add-on therapy: Rifaximin

   • Dosage: 550 mg twice daily
   • Indicated for reducing risk of overt HE recurrence
   • Most effective when used with lactulose 2, 5

Nutritional Support

• Provide adequate protein (avoid restriction unless severe intolerance)
• Ensure sufficient caloric intake to prevent catabolism
• Target positive nitrogen balance to prevent sarcopenia 2

Monitoring and Follow-up

• Daily assessment of mental status
• Monitor serum creatinine, electrolytes, and ammonia levels
• Adjust lactulose dose based on bowel movements and mental status 2

Special Considerations

Persistent HE

• Consider evaluation for large portosystemic shunts
• Evaluate for liver transplantation, especially for refractory cases 1, 2

HE with Acute Kidney Injury

• Discontinue nephrotoxic medications
• Adjust lactulose dosage to prevent excessive diarrhea
• For hypovolemic AKI, administer albumin with careful monitoring 2

Prognosis

While HE has traditionally been considered fully reversible, recent evidence suggests that repeated episodes of overt HE may be associated with persistent cognitive deficits, particularly in working memory and learning 1. Liver transplantation should be considered for patients with recurrent or persistent HE 2.