What is the primary treatment for hepatic encephalopathy?

Treatment of Hepatic Encephalopathy

Lactulose is the first-line treatment for hepatic encephalopathy, with rifaximin recommended as an effective add-on therapy for prevention of recurrence. 1, 2, 3

Four-Pronged Approach to Management

The management of hepatic encephalopathy follows a systematic approach:

1. Initiate appropriate care based on severity:

   • Patients with higher grades of HE (grade 3-4) who cannot protect their airway should be treated in the ICU 1, 2
   • Glasgow coma score less than 7 indicates endangered respiratory function requiring ICU management 1

2. Identify and treat alternative causes of altered mental status:

   • Exclude other causes of brain dysfunction through appropriate testing 1, 2
   • Technically, if other causes are present, the episode may not be termed HE 1

3. Identify and correct precipitating factors:

   • Nearly 90% of patients can be treated with just correction of precipitating factors 1, 4
   • Common precipitating factors include infections, GI bleeding, electrolyte disturbances, and medication non-compliance 2

4. Commence empirical HE treatment:

   • Start pharmacological therapy without delay 1, 2

First-Line Treatment: Lactulose

• Start lactulose at 25 mL orally every 12 hours, titrated to achieve 2-3 soft bowel movements daily 1, 2, 3
• Lactulose works by acidifying the gastrointestinal tract, inhibiting ammonia production by coliform bacteria 5
• In patients unable to take oral medications, administer lactulose via nasogastric tube 1, 4
• Lactulose reduces the risk of HE recurrence by 20% vs. 47% among those who do not receive it 1

Second-Line and Add-On Treatments

• Rifaximin: Add rifaximin 550 mg twice daily when lactulose alone fails to prevent recurrence of HE 1, 6

• Rifaximin decreases intestinal production and absorption of ammonia by altering gastrointestinal flora 5

• Rifaximin reduces the risk of HE recurrence by 58% when added to lactulose (22.1% vs. 45.9% in placebo) 1, 6

• Alternative options when standard therapy fails:

  • Oral Branched-Chain Amino Acids (BCAAs) can be used for patients not responding to conventional therapy 1, 2
  • IV L-Ornithine L-Aspartate (LOLA) is an alternative for non-responders, improving psychometric testing and reducing ammonia levels 1, 2
  • Neomycin and metronidazole are alternative choices but have significant toxicity with long-term use 1, 2

Prevention of Recurrence

• Secondary prophylaxis after an episode of overt HE is strongly recommended 1
• Lactulose is recommended as secondary prophylaxis following a first episode of overt HE 1
• For patients with recurrent HE (>1 additional episode within 6 months), add rifaximin 550 mg twice daily to lactulose 1, 6

Special Considerations

• Consider liver transplantation in patients with recurrent intractable HE and liver failure 1
• A first episode of overt HE should prompt referral to a transplant center for evaluation 1
• For patients with preserved liver function and recurrent HE, evaluate for large spontaneous portosystemic shunts that may be amenable to embolization 4

Common Pitfalls to Avoid

• Overuse of lactulose can paradoxically precipitate HE and cause complications such as aspiration, dehydration, hypernatremia, and perianal skin irritation 2, 4
• Failure to identify and treat precipitating factors is a common reason for poor treatment response 1, 4
• Delaying treatment while awaiting diagnostic confirmation can worsen outcomes 2
• Protein restriction should be avoided as it can worsen malnutrition and sarcopenia, which are risk factors for HE 4

Monitoring and Follow-up

• Titrate lactulose dose to achieve 2-3 soft bowel movements daily 1, 7
• Regularly assess for medication side effects, particularly with long-term use of antibiotics 2
• Monitor for improvement in mental status and ammonia levels, which typically decrease by 25-50% with effective therapy 3