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, 2, 3

First-Line Management

1. Identify and treat precipitating factors (Grade II-2, A, 1) 2

   • Infections
   • GI bleeding
   • Electrolyte disturbances (particularly hypokalemia)
   • Dehydration
   • Constipation
   • Medication non-compliance

2. Lactulose therapy (Grade II-1, B, 1) 2, 3

   • Initial dosing: 25-30 mL orally every 1-2 hours until 2 bowel movements are achieved
   • Maintenance dosing: Titrate to achieve 2-3 soft stools per day
   • Mechanism: Reduces ammonia absorption by trapping NH4+ in the colon through acidification 4
   • Lactulose enemas (300 mL in 700 mL water) can be used when oral administration is not possible

Second-Line and Add-On Therapy

1. Rifaximin (Grade I, A, 1) 2, 5

   • Dosage: 550 mg orally twice daily 5
   • Most effective as add-on to lactulose for prevention of HE recurrence
   • FDA-approved for reduction in risk of overt HE recurrence 5
   • In clinical trials, 91% of patients were using lactulose concomitantly 5

2. For patients not responsive to conventional therapy:

   • Oral Branched-Chain Amino Acids (BCAAs) (Grade I, B, 2) 2, 1

     • Improves manifestations of both overt and minimal HE

   • IV L-Ornithine L-Aspartate (LOLA) (Grade I, B, 2) 2, 1

     • Improves psychometric testing and reduces ammonia levels
     • Note: Oral LOLA is ineffective 2

Alternative Options (for short-term use only)

1. Neomycin (Grade II-1, B, 2) 2, 1

   • Limited by ototoxicity and nephrotoxicity with long-term use
   • Acts as a glutaminase inhibitor 2

2. Metronidazole (Grade II-3, B, 2) 2, 1

   • Only for short-term therapy due to neurotoxicity concerns with long-term use

Management of Severe HE (Grade III-IV)

• Admit to ICU for patients with grade III-IV HE 1
• Secure airway if Glasgow Coma Scale <7 1
• Position head elevated at 30 degrees to reduce risk of aspiration 1

Monitoring and Ongoing Management

• Perform frequent neurological assessments to monitor mental status improvement 1
• Ensure adequate bowel movements (2-3 per day) through lactulose dose titration 1
• Consider liver transplantation evaluation for patients with recurrent or persistent HE 1

Emerging Therapies

• Glyceryl phenylbutyrate (GPB) has shown promise in reducing HE episodes and hospitalizations in patients with two or more previous HE episodes 2
• Albumin administration may improve post-discharge survival but does not affect resolution of HE 2
• Probiotics have shown similar efficacy to lactulose in some studies but are not yet recommended as first-line therapy 2

Important Caveats

• Rifaximin has not been extensively studied in patients with MELD scores >25 5
• Simple laxatives alone do not have the prebiotic properties of disaccharides and are not recommended as alternatives to lactulose 2
• Routine prophylactic therapy is not recommended for prevention of post-TIPS HE 1
• Monitor for Clostridium difficile-associated diarrhea, especially with rifaximin use 5