What are the treatment options for hepatic (liver) encephalopathy?

From the Guidelines

The treatment of hepatic encephalopathy should prioritize lactulose as the first-line therapy, with rifaximin added to reduce gut bacterial ammonia production, as recommended by the most recent guidelines 1. The goal of treatment is to address the underlying causes, reduce ammonia levels, and manage symptoms.

• Lactulose, a non-absorbable disaccharide, should be administered orally at a dose of 20–30 g, 3–4 times per day, with the goal of achieving two to three soft stools per day 1.
• Rifaximin, a non-absorbable antibiotic, can be added at a dose of 400 mg three times/day or 550 mg twice/day to reduce gut bacterial ammonia production 1.
• For acute episodes, lactulose can be given as an enema (200 g in 700 mL water) if oral administration isn't possible 1.
• Precipitating factors, such as infections, gastrointestinal bleeding, electrolyte disturbances, constipation, and medication side effects, must be identified and treated 1.
• For patients with recurrent episodes, long-term maintenance therapy with lactulose and rifaximin significantly reduces relapse rates, as suggested by the French recommendations 1.
• Branched-chain amino acids may benefit patients who remain symptomatic despite standard therapy, and therapeutic education programs can improve quality of life and limit hospitalizations 1. Key considerations in the treatment of hepatic encephalopathy include:
• Identifying and managing precipitating factors 1
• Using lactulose and rifaximin to reduce ammonia production and absorption in the gut 1
• Providing therapeutic education programs to improve quality of life and limit hospitalizations 1

From the FDA Drug Label

XIFAXAN is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults. In the trials of XIFAXAN for HE, 91% of the patients were using lactulose concomitantly. For the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma.

The treatment of hepatic encephalopathy can be managed with rifaximin (XIFAXAN) at a dose of one 550 mg tablet taken orally two times a day, and lactulose.

• Rifaximin is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults.
• Lactulose is indicated for the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma. It is notable that in the trials of rifaximin for HE, 91% of the patients were using lactulose concomitantly 2 3.

From the Research

Treatment Options for Hepatic Encephalopathy

• The primary treatment for hepatic encephalopathy (HE) involves reducing blood ammonia levels, with lactulose and rifaximin being commonly used drugs 4, 5, 6, 7.
• A study comparing rifaximin plus lactulose with lactulose alone found that the combination therapy was more effective in treating overt HE, with a significant decrease in mortality and hospital stay 4.
• Lactulose is often used as the first-line therapy for HE, with rifaximin added as a secondary prophylaxis to prevent recurrent episodes and improve quality of life 6.
• Branched-chain amino acids (BCAA) have also been shown to have beneficial effects on HE manifestations, particularly when used as oral supplements 7.

Multidisciplinary Approach to HE Management

• HE is a complex disease that requires a multidisciplinary approach, involving specialists from hepatology, primary care, neurology, psychiatry, and other disciplines 6.
• A multidisciplinary team approach is essential for managing HE, particularly in screening and treating minimal HE (MHE) in patients with liver cirrhosis 6.
• The management of HE involves identifying and correcting precipitating causes, as well as providing supportive care and treatment to improve quality of life 5, 8.

Current Research and Future Directions

• Despite advances in understanding the pathophysiological basis of HE, there is still a need for more effective therapies, particularly for minimal HE 8.
• Current research focuses on targeting ammonia accumulation and inflammation, with future approaches aiming to develop new therapies for HE 8.
• The combination of lactulose, rifaximin, and BCAA may be a promising treatment strategy for HE, although more evidence is needed to support its effectiveness 7.