What is the treatment for hepatic encephalopathy?

From the Guidelines

The treatment for hepatic encephalopathy should prioritize the use of non-absorbable disaccharides, such as lactulose, as the first-line medication, with a recommended dose of 20-30 g orally 3-4 times per day, as stated in the most recent guidelines 1. The goal of treatment is to reduce ammonia levels in the body by addressing the underlying causes of hepatic encephalopathy.

• Identifying and treating precipitating factors, such as infections, gastrointestinal bleeding, electrolyte disturbances, or medication non-compliance, is crucial in managing acute episodes.
• Lactulose should be administered orally until the patient is having at least 2 bowel movements a day, and then the dose should be titrated to achieve two to three soft stools per day, as recommended in the guidelines 1.
• Rifaximin, a non-absorbable antibiotic, may be added to reduce ammonia-producing gut bacteria, with a recommended dose of 400 mg three times a day or 550 mg twice a day, as stated in the guidelines 1.
• For severe or refractory cases, other treatment options, such as L-ornithine L-aspartate, zinc supplementation, or probiotics, may be considered, as suggested in the guidelines 1.
• Protein restriction is no longer routinely recommended; instead, patients should maintain adequate protein intake (1.2-1.5 g/kg/day) with emphasis on vegetable and dairy protein sources, as recommended in the guidelines 1.
• Branched-chain amino acid supplements may benefit some patients who cannot tolerate dietary protein, as suggested in the guidelines 1. The most recent and highest quality study, published in 2023, recommends the use of non-absorbable disaccharides, such as lactulose, as the first-line treatment for hepatic encephalopathy, with rifaximin as an add-on therapy for patients who do not respond to lactulose alone 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, often used concomitantly with lactulose 3. Key points:
• Lactulose reduces blood ammonia levels and improves mental state and EEG patterns.
• Rifaximin is used to reduce the risk of HE recurrence, with a recommended dose of one 550 mg tablet taken orally two times a day.

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 for the treatment of overt hepatic encephalopathy in 2010 4.
• Rifaximin decreases intestinal production and absorption of ammonia by altering gastrointestinal flora and is almost completely excreted unchanged in the feces 4.

Combination Therapy

• Combination therapy with rifaximin and lactulose has been shown to be effective in improving behavioral, laboratory, mental, and intellectual abnormalities in patients with hepatic encephalopathy 5, 6.
• A meta-analysis of randomized trials found that the addition of rifaximin to non-absorbable disaccharides was more beneficial than non-absorbable disaccharides used alone 5.
• Another study found that the use of rifaximin plus lactulose was associated with an increased incidence of effective rate and reduced risk of mortality compared to lactulose alone 6.

Other Treatment Options

• Branched chain amino acids (BCAA) have been shown to have beneficial effects on manifestations of hepatic encephalopathy compared to control supplements 5.
• Lactulose enemas can be used instead of or in combination with oral lactulose to treat hepatic encephalopathy 7.
• Disaccharides, such as lactulose and lactitol, are considered first-line therapy for the treatment of hepatic encephalopathy and minimal hepatic encephalopathy (MHE) 8.