What are the stages and management of Hepatic Encephalopathy?

Stages of Hepatic Encephalopathy

Hepatic encephalopathy should be graded using the West Haven Criteria, which divides the spectrum into five stages (0-IV), ranging from covert HE (minimal HE and Grade I) to coma (Grade IV), with the Glasgow Coma Scale added for Grades III-IV to improve objectivity. 1

Classification System

The West Haven Criteria provides the standard grading framework 1:

Covert Hepatic Encephalopathy

• Grade 0 (Minimal HE): No obvious clinical signs but abnormalities detected on neuropsychological or neurophysiological testing 2, 3
• Grade I: Mild alterations in consciousness, subtle personality or behavior changes, decreased attention, sleep disturbances (sleep-wake inversion), irritability or apathy, and difficulty performing complex cognitive tasks 2, 3

Overt Hepatic Encephalopathy

• Grade II: Mild disorientation (especially temporal), more pronounced lethargy or apathy, inappropriate behavior, asterixis, dysarthric or slow speech, and evident alterations in psychometric tests 1, 3
• Grade III: Marked confusion, incoherent speech, sleeping most of the time but arousable to vocal stimuli, gross disorientation, and somnolence 1
• Grade IV: Comatose, unresponsive to pain, decorticate or decerebrate posturing 1

Additional Classification Dimensions

Beyond severity grading, HE must be classified by three other factors 1:

Type (Based on Underlying Disease)

• Type A: Resulting from acute liver failure (distinct features including risk of increased intracranial pressure and cerebral herniation) 1
• Type B: Resulting predominantly from portosystemic bypass or shunting without significant liver disease 2
• Type C: Resulting from cirrhosis with or without portosystemic shunt 1, 2

Time Course

• Episodic HE: Isolated episodes 1
• Recurrent HE: Bouts occurring with intervals of 6 months or less 1
• Persistent HE: Behavioral alterations always present, interspersed with relapses of overt HE 1

Precipitating Factors

• Precipitated: Identify specific triggers (infections in 64%, acute kidney injury in 63%, drugs in 41%, GI bleeding in 36%, hyponatremia in 22%, TIPS in 12%, constipation in 1%) 1, 4
• Non-precipitated: No identifiable trigger 1

Management Approach by Stage

Grade 0-I (Covert HE)

Management on a general medicine ward is appropriate, with testing for covert HE considered only in patients with impaired quality of life, employment implications, or public safety concerns (e.g., driving ability). 1, 2, 3

• Perform systematic investigation for signs: asterixis, psychomotor slowing, sleep-wake inversion, temporospatial disorientation 3
• Use animal naming test or validated neuropsychological testing (PHES, CRT, ICT, SCAN, Stroop) or neurophysiological tests (CFF, EEG) for diagnosis 1, 3
• Treatment is not routinely recommended but may be considered when affecting daily functioning, work performance, or driving ability 1
• Perform frequent mental status checks with transfer to ICU if consciousness declines 3

Grade II

Lactulose is first-line treatment, titrated to achieve 2-3 soft stools per day, combined with aggressive identification and correction of precipitating factors. 2, 3, 5

• Initial dosing: 30-45 mL (20-30 grams) three to four times daily orally 5
• Rapid laxation phase: Hourly doses of 30-45 mL may be used initially 5
• Maintenance: Reduce to recommended daily dose once laxative effect achieved 5
• Identify and treat precipitating factors (infections, GI bleeding, constipation, dehydration, electrolyte disturbances, sedative medications), which resolve up to 90% of cases 3, 4
• Brain CT imaging should be performed to exclude intracranial hemorrhage and other causes of altered mental status 1
• ICU setting is indicated if consciousness continues to decline 1, 3

Grade III-IV

Intubate for airway protection and transfer to ICU immediately due to risk of aspiration, cerebral edema, and herniation. 1, 2, 6

• Airway management: Intubate patients progressing to Grade III-IV for airway protection 1, 6
• Sedation: Use short-acting agents (propofol or dexmedetomidine); avoid benzodiazepines which worsen HE and have delayed clearance 1, 6
• Positioning: Elevate head to 30 degrees 1
• Lactulose administration:
  • Via nasogastric tube if tolerated 6
  • As retention enema if aspiration risk or ileus: 300 mL lactulose mixed with 700 mL water/saline, retained 30-60 minutes, repeated every 4-6 hours 5, 7
• Add Glasgow Coma Scale to West Haven Criteria for objective monitoring 1, 2
• Seizure management: Control with phenytoin; use minimal benzodiazepines only if necessary 1
• Monitor closely: Glucose, potassium, magnesium, phosphate, hemodynamics, renal function 1, 3

Critical Management Principles

Four-Pronged Approach (All Grades)

1. Initiate care for altered consciousness (airway protection if needed) 1, 2
2. Identify and treat alternative causes of altered mental status 1, 2
3. Identify and correct precipitating factors 1, 2
4. Commence empirical HE treatment 1, 2

Prophylaxis Recommendations

• Secondary prophylaxis: Recommended after first episode of overt HE with lactulose maintenance 1, 3
• Primary prophylaxis: Not required except in cirrhotic patients at high risk for developing HE 1
• Rifaximin: Consider as add-on therapy for recurrent episodes despite lactulose 2, 8

Liver Transplantation

Recurrent intractable overt HE together with liver failure is an indication for liver transplantation evaluation. 1, 3

Diagnostic Considerations

Ammonia Testing

• Blood ammonia levels alone do not add diagnostic, staging, or prognostic value 1, 2, 3
• A normal ammonia level in suspected HE calls for diagnostic reevaluation 1
• Arterial ammonia >200 μg/dL strongly associated with cerebral herniation in acute liver failure 1

Brain Imaging

• CT or MRI does not contribute to grading but should be performed to exclude intracranial hemorrhage (5-fold increased risk) and other pathology, especially for first-time HE 1

Differential Diagnosis

Exclude other causes of altered mental status 1:

• Diabetic emergencies (hypoglycemia, ketoacidosis, hyperosmolar state) 1
• Alcohol-related (intoxication, withdrawal, Wernicke encephalopathy) 1
• Drug effects (benzodiazepines, neuroleptics, opioids) 1
• Neuroinfections 1
• Electrolyte disorders (hyponatremia, hypercalcemia) 1
• Nonconvulsive epilepsy 1
• Intracranial bleeding and stroke 1

Common Pitfalls to Avoid

• Failing to identify and treat precipitating factors, which cause up to 90% of cases and include multiple concomitant factors in 82% of ICU admissions 3, 4
• Inadequate lactulose titration: Must achieve 2-3 soft stools per day 2, 3
• Relying solely on ammonia levels for diagnosis or monitoring 1, 2, 3
• Not considering secondary prophylaxis after the first episode of overt HE 2, 3
• Confusing HE with other causes of altered mental status without proper differential diagnosis 1, 2, 3
• Delaying intubation in Grade III-IV when aspiration risk is present 1, 6
• Using benzodiazepines for sedation, which worsen HE and have delayed clearance 1, 6