What is the treatment for hepatic encephalopathy?

Treatment of Hepatic Encephalopathy

Lactulose is the first-line treatment for hepatic encephalopathy, with rifaximin as an effective add-on therapy for prevention of recurrence. 1

Four-Pronged Approach to Management

The recommended approach to managing hepatic encephalopathy (HE) includes:

1. Initiation of care for patients with altered consciousness

   • Patients with higher grades of HE who cannot protect their airway require intensive care monitoring 1

2. Identify and treat alternative causes of altered mental status

   • Rule out other causes of encephalopathy that may coexist with HE 1

3. Identify and correct precipitating factors

   • This is of paramount importance as nearly 90% of patients can be treated with just correction of precipitating factors 1
   • Common precipitating factors include infections, GI bleeding, electrolyte disturbances, and medication non-compliance 1

4. Commence empirical HE treatment

   • Begin pharmacological therapy as outlined below 1

Pharmacological Management

First-Line Treatment

• Lactulose
  • FDA-approved for prevention and treatment of portal-systemic encephalopathy 2
  • Initial dosing: 25 mL of lactulose syrup every 12 hours 1
  • Titrate to achieve 2-3 soft bowel movements per day 1
  • Reduces blood ammonia levels by 25-50%, which parallels improvement in mental state 2
  • Clinical response observed in approximately 75% of patients 2
  • Caution: Overuse can lead to complications including aspiration, dehydration, hypernatremia, and severe perianal skin irritation 1

Add-on/Alternative Therapies

• Rifaximin

  • FDA-approved for reduction in risk of overt HE recurrence 3
  • Recommended dose: 550 mg orally twice daily 3
  • Most effective when used with lactulose (91% of patients in clinical trials used concomitant lactulose) 3
  • Superior to placebo for maintenance of remission in patients who have already experienced one or more episodes of overt HE 1
  • No solid data support the use of rifaximin alone 1

• Oral Branched-Chain Amino Acids (BCAAs)

  • Can be used as an alternative or additional agent for patients not responding to conventional therapy 1
  • Meta-analyses show improvement in manifestations of episodic HE 1

• IV L-Ornithine L-Aspartate (LOLA)

  • Alternative for patients not responding to conventional therapy 1
  • Improves psychometric testing and reduces postprandial venous ammonia levels 1
  • Note: Oral supplementation with LOLA is ineffective 1

• Antibiotics (Neomycin, Metronidazole)

  • Alternative choices for treatment of overt HE 1
  • Long-term use limited by ototoxicity, nephrotoxicity, and neurotoxicity 1, 4

Prevention of Recurrence

• Secondary prophylaxis after an episode of overt HE is strongly recommended 1

  • Lactulose is widely recommended despite limited randomized controlled trial data 1
  • Rifaximin added to lactulose is the best-documented regimen for maintaining remission 1

• Primary prophylaxis is not required except in patients with cirrhosis at high risk for developing HE 1

Special Considerations

Post-TIPS Hepatic Encephalopathy

• Neither rifaximin nor lactulose has been shown to prevent post-TIPS HE better than placebo 1
• If severe HE occurs after TIPS, shunt diameter reduction may be necessary 1

Recurrent Intractable HE

• Recurrent intractable overt HE, together with liver failure, is an indication for liver transplantation 1
• For patients with preserved liver function, consider evaluating for large spontaneous portosystemic shunts 1

Monitoring and Follow-up

• Monitor response to therapy through clinical improvement in mental status 2
• The Bristol stool scale can help guide lactulose titration 5
• Regularly assess for medication side effects, particularly with long-term use of antibiotics 1

Common Pitfalls to Avoid

• Overuse of lactulose can paradoxically precipitate HE and cause other complications 1
• Failure to identify precipitating factors may lead to poor treatment response 1
• Relying solely on ammonia levels for diagnosis or treatment monitoring is not recommended, as clinical correlation is more important 6
• Delaying treatment while awaiting diagnostic confirmation can worsen outcomes 1

Remember that controlling precipitating factors is the cornerstone of HE management, with pharmacological therapy serving as an important adjunct to this approach 1, 7.