What are the signs and treatment options for hepatic encephalopathy?

Hepatic Encephalopathy: Signs and Treatment

Clinical Signs and Diagnosis

Hepatic encephalopathy presents as a continuum from subtle cognitive impairment to coma, diagnosed by excluding other causes of altered mental status. 1

Overt Hepatic Encephalopathy (OHE)

• Graded using West Haven Criteria (WHC) and Glasgow Coma Scale (GCS) to assess severity from grade I (mild confusion, altered sleep) through grade IV (coma) 1
• Patients with grade III-IV cannot protect their airway and require immediate intubation 2, 3
• Brain imaging is typically performed on first presentation to exclude intracranial hemorrhage, which occurs 5-fold more frequently in cirrhotic patients 1

Minimal Hepatic Encephalopathy (MHE)

• Not apparent on routine clinical examination but detected through neurophysiological and psychometric testing by experienced examiners 1
• Testing should be considered when impairment affects driving, work performance, or quality of life 1

Diagnostic Pitfall

• Elevated ammonia levels do not add diagnostic, staging, or prognostic value; however, a normal ammonia level should prompt reevaluation for alternative diagnoses 1

Treatment Approach

The cornerstone of hepatic encephalopathy management is identifying and correcting precipitating factors, which successfully treats nearly 90% of patients, combined with lactulose as first-line pharmacotherapy. 1, 4

Four-Pronged Management Strategy

1. Airway Protection and Intensive Care

• Intubate immediately for grade III-IV encephalopathy due to aspiration risk and loss of protective reflexes 2, 3
• Elevate head of bed to 30 degrees to reduce intracranial pressure 2, 3
• Transfer patients unable to protect their airway to intensive care 1

2. Identify and Treat Precipitating Factors

This is the most critical step—90% of patients improve with precipitating factor correction alone 1, 4

Common precipitating factors to evaluate and treat: 4, 2

• Gastrointestinal bleeding: Check CBC, digital rectal exam, stool blood test; perform endoscopy; treat with transfusion and endoscopic therapy 2
• Infection: Obtain CBC with differential, CRP, chest X-ray, urinalysis with culture, blood cultures, and diagnostic paracentesis if ascites present; start antibiotics 2
• Electrolyte disturbances: Monitor and correct imbalances 4
• Medication non-compliance: Verify adherence to lactulose regimen 4

3. Rule Out Alternative Causes

• Alternative causes of encephalopathy are common in advanced cirrhosis and must be excluded 1
• Consider intracranial hemorrhage, infection, metabolic derangements, and medication effects 1

4. Pharmacological Treatment

First-Line: Lactulose

Lactulose is FDA-approved and recommended as initial treatment for all episodes of overt hepatic encephalopathy 4, 5

• Emergency dosing: 30-45 mL (20-30 g) every 1-2 hours orally or via nasogastric tube until at least 2 bowel movements occur 2
• Maintenance dosing: 25 mL every 12 hours, titrated to achieve 2-3 soft bowel movements per day 1, 4
• Nasogastric tube administration is appropriate for patients unable to swallow or at aspiration risk 1
• Clinical response occurs in approximately 75% of patients 5

Critical pitfall: Overuse of lactulose can paradoxically precipitate hepatic encephalopathy through excessive diarrhea and electrolyte disturbances 4

Second-Line: Rifaximin

Rifaximin (550 mg twice daily) is FDA-approved for reducing risk of overt hepatic encephalopathy recurrence and should be added to lactulose for secondary prophylaxis 4, 6

• Most effective when used in combination with lactulose (91% of trial patients used both) 6
• Not studied in patients with MELD scores >25; only 8.6% of trial patients had MELD >19 6
• Nearly completely excreted unchanged in feces with minimal systemic absorption 7

Alternative Agents

When patients fail to respond to lactulose: 4

• Oral branched-chain amino acids (BCAAs): Meta-analyses show improvement in episodic hepatic encephalopathy manifestations 4
• IV L-ornithine L-aspartate (LOLA): Improves psychometric testing and reduces postprandial ammonia 4
• Antibiotics (neomycin, metronidazole): Limited by ototoxicity, nephrotoxicity, and neurotoxicity with long-term use 4

Management of Agitation

For mild-to-moderate agitation, use haloperidol 0.5-5 mg PO/IM every 8-12 hours 4, 2, 3

Critical contraindication: Avoid benzodiazepines—they have delayed clearance in liver failure and worsen encephalopathy 2, 3

For severe agitation requiring sedation in intubated patients: 3

• Propofol in small doses is preferred if sedation is absolutely necessary 3
• Minimize sedatives as they interfere with neurological assessment and mask underlying encephalopathy 3

Prophylaxis Strategies

Secondary Prophylaxis (After First Episode)

Secondary prophylaxis is strongly recommended after any episode of overt hepatic encephalopathy 1, 4

• Best-documented regimen: Lactulose plus rifaximin for maintaining remission 4
• Continue indefinitely or until liver transplantation 1

Primary Prophylaxis

• Not routinely recommended except in cirrhotic patients at known high risk for developing hepatic encephalopathy 1, 4
• Neither rifaximin nor lactulose prevents post-TIPS hepatic encephalopathy better than placebo 4

Nutritional Management

Do not restrict protein intake—protein restriction increases catabolism and worsens outcomes 2

• Patients with mild hepatic encephalopathy can be fed orally if cough and swallow reflexes are intact 2

Indications for Liver Transplantation

Recurrent intractable overt hepatic encephalopathy with liver failure is an indication for liver transplantation 1, 4

• For patients with preserved liver function and recurrent encephalopathy, evaluate for large spontaneous portosystemic shunts that may require intervention 4
• Consider shunt diameter reduction if severe hepatic encephalopathy occurs after TIPS 4

Monitoring Parameters

• Perform frequent neurological evaluations for signs of intracranial hypertension 2, 3
• Monitor hemodynamic parameters, renal function, glucose, and electrolytes 2, 3
• Do not use ammonia levels for monitoring—they do not correlate with encephalopathy severity or prognosis 2
• Assess for medication side effects, particularly with long-term antibiotic use 4

Common Pitfalls to Avoid

• Failure to identify precipitating factors leads to poor treatment response—always search systematically 4, 2
• Delaying treatment while awaiting diagnostic confirmation worsens outcomes—start empirical therapy immediately 4
• Using benzodiazepines for agitation worsens encephalopathy—use haloperidol instead 2, 3
• Excessive lactulose causing dehydration and electrolyte disturbances can paradoxically worsen encephalopathy 4