How to treat resistant hepatic encephalopathy?

From the Guidelines

Treatment of resistant hepatic encephalopathy should prioritize a multifaceted approach, starting with lactulose and rifaximin, and considering additional therapies such as branched-chain amino acids and zinc supplementation, as supported by the most recent guidelines 1. The management of resistant hepatic encephalopathy involves several key strategies:

• Increasing the dose of lactulose to achieve 2-3 soft bowel movements daily, with a typical starting dose of 20-30 g orally 3-4 times per day, as recommended by the KASL clinical practice guidelines 1.
• Adding rifaximin 400 mg three times a day or 550 mg twice a day to reduce ammonia-producing bacteria, as suggested by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases 1.
• Considering the addition of branched-chain amino acids (0.25 g/kg/day) to improve nitrogen metabolism, as recommended by the KASL clinical practice guidelines 1.
• Addressing precipitating factors, such as infections, electrolyte imbalances, and constipation, is crucial in the management of hepatic encephalopathy, as emphasized by the French recommendations 1.
• In severe cases, albumin dialysis or continuous renal replacement therapy may be employed to remove ammonia directly from circulation, and liver transplantation should be considered for patients who do not respond to medical treatments, as recommended by the KASL clinical practice guidelines 1. The use of non-absorbable disaccharides, such as lactulose, is supported by a systematic review and meta-analysis, which found that lactulose or lactitol was more effective in improving symptoms than placebo, with a relative risk of 0.62 (95% CI, 0.46-0.84) 1. Overall, the treatment of resistant hepatic encephalopathy requires a comprehensive approach that addresses the underlying pathophysiology and precipitating factors, and considers the use of multiple therapies to improve patient outcomes.

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. In the trials of XIFAXAN for HE, 91% of the patients were using lactulose concomitantly.

The treatment for resistant hepatic encephalopathy may involve the use of lactulose and rifaximin.

• Lactulose is indicated for the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma 2.
• Rifaximin is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults, and is often used concomitantly with lactulose 3. Key points:
• The recommended dose of rifaximin for hepatic encephalopathy is one 550 mg tablet taken orally two times a day 3.
• Lactulose has been shown to reduce blood ammonia levels and improve mental state and EEG patterns in patients with portal-systemic encephalopathy 2.

From the Research

Treatment Options for Resistant Hepatic Encephalopathy

• Lactulose is considered the first-line therapeutic agent for treating hepatic encephalopathy, as it acidifies the gastrointestinal tract and inhibits production of ammonia by coliform bacteria 4.
• Rifaximin, a semisynthetic, nonsystemic antibiotic, has been approved for the treatment of overt hepatic encephalopathy and has been found to be equal or superior to lactulose in some studies 4, 5.
• The combination of lactulose and rifaximin has been shown to be more beneficial than using either medication alone 5.
• Branched-chain amino acids (BCAA) have also been found to have beneficial effects on manifestations of hepatic encephalopathy, particularly when used in combination with lactulose or rifaximin 5, 6.
• Other treatment options, such as L-ornithine L-aspartate, ornithine phenylacetate, spherical carbon, and fecal microbiota transplant, are being studied and may potentially have beneficial effects on hepatic encephalopathy manifestations 6.

Management of Resistant Hepatic Encephalopathy

• Patients who do not respond to lactulose and rifaximin should be investigated for other causes of altered sensorium 7.
• The use of neomycin, a systemic antibiotic, may be considered in combination with lactulose for patients who have not responded adequately to lactulose alone 8.
• Recent studies suggest that newer treatments, such as fecal microbiota transplant, may have potentially beneficial effects on hepatic encephalopathy manifestations, but more research is needed to validate these findings 6.