What is the first line treatment for hepatic (liver) encephalopathy?

From the Guidelines

The first line treatment for hepatic encephalopathy is lactulose, a non-absorbable disaccharide, typically administered at an initial dose of 20-30 g orally 3-4 times per day. This recommendation is based on the most recent and highest quality study available, which suggests that lactulose is effective in reducing ammonia levels and improving symptoms of hepatic encephalopathy 1. The goal of treatment is to reduce ammonia levels, which are neurotoxic and primarily responsible for the neuropsychiatric symptoms of hepatic encephalopathy. Lactulose works by acidifying the colon, which traps ammonia as ammonium and prevents its absorption. It also has a cathartic effect that helps eliminate nitrogen-containing compounds from the intestines.

Key Points to Consider

• 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 1.
• If patients cannot take medications orally, administration via nasogastric tube might be tried, or an enema with lactulose 200 g and 700 mL water can be performed 3-4 times per day in severe cases 1.
• Rifaximin, a non-absorbable antibiotic (400 mg three times/day or 550 mg twice/day), is often added as an adjunct therapy, particularly for patients with recurrent episodes 1.
• Additional management should include identifying and treating precipitating factors such as gastrointestinal bleeding, infection, electrolyte disturbances, or medication non-compliance, as these can worsen encephalopathy even with appropriate lactulose therapy 1.

Treatment Approach

The treatment approach for hepatic encephalopathy should prioritize the use of non-absorbable disaccharides, such as lactulose, as the first line treatment. Rifaximin can be added as an adjunct therapy in patients with recurrent episodes. It is also important to identify and treat precipitating factors, and to monitor the patient's response to treatment and adjust the dose of lactulose as needed.

Evidence Summary

The evidence suggests that lactulose is effective in reducing ammonia levels and improving symptoms of hepatic encephalopathy 1. The use of rifaximin as an adjunct therapy has also been shown to be effective in preventing recurrence of hepatic encephalopathy 1. The treatment approach should prioritize the use of non-absorbable disaccharides, such as lactulose, and identify and treat precipitating factors.

From the FDA Drug Label

For the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma. Controlled studies have shown that lactulose solution therapy reduces the blood ammonia levels by 25 to 50%; this is generally paralleled by the improvement in the patients’ mental state and by an improvement in EEG patterns.

The first line treatment for hepatic (liver) encephalopathy is lactulose (PO), as it has been shown to reduce blood ammonia levels and improve mental state in about 75% of patients 2.

From the Research

Hepatic Encephalopathy Treatment

The first line treatment for hepatic (liver) encephalopathy is typically a nonabsorbable disaccharide, such as lactulose, which is considered the first-line therapeutic agent for treating hepatic encephalopathy 3.

Key Points

• Lactulose works by acidifying the gastrointestinal tract, which inhibits the production of ammonia by coliform bacteria 3.
• Elevated ammonia levels are seen in more than 80% of patients with hepatic encephalopathy 3.
• Rifaximin, a semisynthetic, nonsystemic antibiotic, is also used to treat hepatic encephalopathy and has been shown to be effective in improving behavioral, laboratory, mental, and intellectual abnormalities in patients with the condition 3, 4.
• The addition of rifaximin to lactulose therapy may result in substantial reductions in healthcare resource utilization over the long term, by reducing overt HE recurrence and associated rehospitalization 4.

Treatment Options

• Lactulose is effective for the prevention of overt HE recurrence over the long term 4.
• Rifaximin can be used alone or in combination with lactulose to treat hepatic encephalopathy 3, 4.
• Other treatment options, such as zinc, antibiotics (neomycin, metronidazole), ornithine aspartate, sodium benzoate, probiotics, and surgical intervention, may be considered as second-line treatments or in specific cases 5.