From the Guidelines
The primary therapy for hepatic encephalopathy is lactulose, a non-absorbable disaccharide, which should be administered orally until the patient is having at least 2 bowel movements a day, then titrated to achieve two to three soft stools per day, as recommended by the most recent guidelines 1.
Key Considerations
- Lactulose should be started at a dose of 20-30 g orally 3-4 times per day, with an equivalent daily dose of lactitol being 67-100 g 1.
- Rifaximin, a non-absorbable antibiotic, can be added at 400 mg three times/day or 550 mg twice/day for patients who have recurrent episodes or inadequate response to lactulose alone 1.
- For acute episodes, lactulose can be administered as an enema (200 g in 700 mL water) 3-4 times per day in severe cases 1.
- Treatment should also address precipitating factors such as gastrointestinal bleeding, infection, electrolyte disturbances, constipation, or medication non-compliance, as outlined in the diagnostic tests and treatments for precipitating factors 1.
Additional Therapies
- Oral BCAA (0.25 g/kg/day) and intravenous LOLA (30 g/day) may be considered as adjunctive therapies 1.
- Albumin (1.5 g/kg/day) may be administered until clinical improvement or for 10 days, maximum 1.
- Polyethylene glycol can be used as a substitute for non-absorbable disaccharides, with a dose of 4 liters orally 1.
Quality of Life and Recurrence Prevention
- A therapeutic education program should be offered to the patient and caregiver to improve quality of life and limit hospitalizations, as suggested by the French recommendations 1.
- Rifaximin can be used alone to prevent recurrence of hepatic encephalopathy when lactulose is poorly tolerated in patients with cirrhosis, with a dose of 550 mg twice daily 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.
Therapy for Hepatic Encephalopathy:
- Lactulose (PO) is indicated for the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma 2.
- Rifaximin (PO) is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults 3. Key Points:
- Lactulose has been shown to reduce blood ammonia levels and improve mental state and EEG patterns in patients with hepatic encephalopathy 2.
- Rifaximin has been studied in patients with hepatic encephalopathy, with 91% of patients using lactulose concomitantly 3.
From the Research
Therapy for Hepatic Encephalopathy
- Hepatic encephalopathy (HE) is a complication of liver disease that can be treated with medications such as lactulose and rifaximin 4, 5, 6, 7, 8.
- Lactulose is a non-absorbable disaccharide that helps reduce plasma ammonia concentrations by favoring the formation of non-absorbable NH4+ from NH3 6.
- Rifaximin is an antibiotic that has been shown to be effective in treating HE, particularly when used in combination with lactulose 4, 5, 7, 8.
Combination Therapy
- Studies have investigated the efficacy of combination therapy with rifaximin and lactulose compared to lactulose alone in treating HE 4, 5, 7, 8.
- A randomized controlled trial found that combination therapy with rifaximin and lactulose was more effective than lactulose alone in treating overt HE, with a significant decrease in mortality and hospital stay 4.
- Another study found that add-on rifaximin therapy reduced hospitalization rates and ammonia levels in patients with treatment-resistant HE 5.
- However, other studies have found that combination therapy may not be superior to lactulose alone in treating refractory HE 7, 8.
Treatment Outcomes
- Treatment outcomes for HE can be measured using various parameters, including mental status grade, asterixis grade, serum ammonia grade, and hepatic encephalopathy index 7.
- Studies have shown that combination therapy with rifaximin and lactulose can improve these parameters, but the evidence is not consistent across all studies 4, 5, 7, 8.
- The use of lactulose enemas may also be effective in treating HE, particularly in patients who are unable to take oral medications 6.