What is the primary 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 in patients who have experienced multiple episodes. 1

Primary Treatment Approach

First-Line Treatment: Lactulose

• Lactulose is FDA-approved for the prevention and treatment of portal-systemic encephalopathy, including hepatic pre-coma and coma 2
• Clinical response occurs in approximately 75% of patients 2
• Dosing recommendations:
  • Initial dose: 25 mL (17 g) every 12 hours orally
  • Titrate to achieve 2-3 soft bowel movements daily 1
  • For patients unable to take oral medications: administration via nasogastric tube
  • For severe HE: lactulose enemas 3-4 times daily until clinical improvement 1
• Maintenance therapy should be continued after the first episode 1

Second-Line/Add-on Treatment: Rifaximin

• Add rifaximin 550 mg orally twice daily for patients with recurrent episodes of HE 1, 3
• Reduces risk of HE recurrence by 58% compared to placebo (NNT = 4) 1
• FDA-approved specifically for reduction in risk of overt hepatic encephalopathy recurrence in adults 3
• In clinical trials, 91% of patients were using lactulose concomitantly 3

Addressing Precipitating Factors

Identifying and treating precipitating factors is crucial and can resolve HE in up to 90% of cases 1:

• Infections
• Gastrointestinal bleeding
• Constipation
• Electrolyte disturbances
• Dehydration
• Sedative medications

Nutritional Management

• Avoid protein restriction as it may worsen nutritional status 1
• Maintain adequate protein intake (1.2-1.5 g/kg/day) to prevent muscle wasting 1
• Provide small, frequent meals throughout the day with a late-night snack 1

Monitoring and Special Considerations

• Patients with high grades of encephalopathy (grades 3-4) require ICU monitoring due to aspiration risk 1
• Secure airway if mental status is severely impaired (Glasgow Coma Scale score <7) 1
• Assess severity using West Haven criteria or Glasgow Coma Scale 1

Potential Complications and Pitfalls

• Lactulose overuse complications: aspiration, dehydration, hypernatremia, severe perianal skin irritation, and paradoxically may precipitate HE 1
• Rifaximin has not been extensively studied in patients with MELD scores >25 3
• Increased systemic exposure to rifaximin occurs in patients with more severe hepatic dysfunction 3

Alternative Therapies

When standard therapy fails, consider:

• L-ornithine L-aspartate (LOLA): 30 g/day IV 1
• Branched-chain amino acids (BCAAs): 0.25 g/kg/day orally 1
• Albumin: 1.5 g/kg/day until clinical improvement or maximum of 10 days 1
• Polyethylene glycol as a substitute for non-absorbable disaccharides 1
• Neomycin (limited by nephrotoxicity and ototoxicity) 1
• Metronidazole (limited by neurotoxicity) 1

Long-term Management

• Consider liver transplantation evaluation in patients with recurrent or persistent HE 1
• Investigate for large spontaneous portosystemic shunts in patients with preserved liver function 1
• Secondary prophylaxis with lactulose has been shown to significantly reduce HE recurrence (19.6% vs 46.8% in placebo) 4