What is the treatment for hepatic encephalopathy?

From the Guidelines

Treatment for hepatic encephalopathy should primarily focus on lactulose administration, with a recommended dose of 20-30 g orally 3-4 times per day, aiming for 2-3 soft stools per day, as supported by the most recent guidelines 1. The goal of treatment is to reduce ammonia levels in the blood and address the underlying liver dysfunction.

• Key treatment strategies include:
  • Lactulose administration, with dose titration to achieve the desired bowel movement frequency
  • Consideration of rifaximin addition at 550 mg twice daily to reduce ammonia-producing gut bacteria, especially in cases of failed prevention with lactulose or lactitol 1
  • Identification and management of precipitating factors, such as infections, gastrointestinal bleeding, or medication non-compliance
  • Avoiding sedatives, managing constipation, and treating infections promptly to prevent recurrence
  • Regular monitoring of ammonia levels, mental status, and liver function to guide ongoing treatment
• Additional treatment options may include:
  • Oral branched-chain amino acid supplements at 0.25 g/kg/day
  • Intravenous L-ornithine-L-aspartate at 30 g/day
  • Albumin administration at 1.5 g/kg/day until clinical improvement or for 10 days, maximum
  • Polyethylene glycol as a substitute for non-absorbable disaccharides, with a dose of 4 liters orally
• For recurrent or refractory cases, liver transplantation may be considered as definitive therapy, as recommended by recent guidelines 1.

From the FDA Drug Label

For the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma. XIFAXAN is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults.

The treatment for hepatic encephalopathy includes:

• Lactulose (PO): for the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma 2.
• Rifaximin (PO): for reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults 3. Key points to consider:
• Lactulose has been shown to reduce blood ammonia levels and improve mental state and EEG patterns in patients with hepatic encephalopathy.
• Rifaximin has been studied in patients with hepatic encephalopathy, but most patients were also using lactulose concomitantly.

From the Research

Treatment Options for Hepatic Encephalopathy

• The nonabsorbable disaccharide, lactulose, is considered the first-line therapeutic agent for treating hepatic encephalopathy 4.
• Lactulose works by acidifying the gastrointestinal tract, which inhibits the production of ammonia by coliform bacteria 4.
• Systemic antibiotics, such as neomycin, have also been used to reduce bacterial production of ammonia, but their use is limited due to adverse events 4.
• Rifaximin, a semisynthetic, nonsystemic antibiotic, was approved in 2010 for the treatment of overt hepatic encephalopathy and has been shown to be effective in improving symptoms 4, 5.

Comparison of Treatment Options

• Rifaximin has been compared to lactulose in clinical studies and was found to be equal or superior in some cases 4.
• The combination of lactulose and rifaximin has been shown to be more effective than lactulose alone in preventing overt hepatic encephalopathy recurrence and reducing healthcare resource utilization 6.
• Branched chain amino acids (BCAA) have also been found to have beneficial effects on hepatic encephalopathy manifestations, particularly when used in combination with non-absorbable disaccharides or rifaximin 7.

Long-Term Management

• Long-term treatment with lactulose and/or rifaximin has been shown to be effective and safe in managing hepatic encephalopathy 6.
• The addition of rifaximin to lactulose therapy has been found to significantly reduce the risk of overt hepatic encephalopathy recurrence and HE-related hospitalization 6.