From the Guidelines
The primary treatment for hepatic encephalopathy to prevent long-term cognitive impairment involves addressing the underlying liver dysfunction and reducing ammonia levels in the body, with lactulose as the cornerstone medication, typically started at 20-30 g orally 3-4 times per day, as recommended by the most recent guidelines 1.
Treatment Overview
The treatment of hepatic encephalopathy (HE) aims to reduce ammonia production and absorption in the gut, which is the primary neurotoxin responsible for brain dysfunction in HE. The management includes:
- Identifying and treating precipitating factors such as gastrointestinal bleeding, infections, electrolyte disturbances, or medication side effects
- Dietary protein moderation, aiming for 1.0-1.5 g/kg/day with emphasis on vegetable and dairy protein sources
- Avoiding alcohol completely and minimizing medications metabolized by the liver
- Regular monitoring of ammonia levels, liver function, and neurological status
Medications
The medications used to treat HE include:
- Lactulose, a non-absorbable disaccharide, which 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
- Rifaximin, a non-absorbable antibiotic, which can be added at a dose of 400 mg three times/day or 550 mg twice/day to further reduce ammonia-producing gut bacteria 1
- Other medications such as oral BCAA, intravenous LOLA, and albumin may also be used in specific cases 1
Recent Guidelines
The most recent guidelines recommend lactulose as the first-line treatment for HE, with rifaximin as an adjunct to lactulose for secondary prophylaxis following more than one episode of overt HE within 6 months of the first one 1. The guidelines also emphasize the importance of identifying and treating precipitating factors, and controlling the progression of the underlying liver disease 1.
Quality of Life
The treatment of HE should prioritize the improvement of quality of life, by reducing the frequency and severity of episodes, and minimizing the risk of long-term cognitive impairment. Regular monitoring and adjustment of treatment are essential to achieve this goal 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.
The treatment for hepatic (liver) encephalopathy to prevent long-term dementia is rifaximin (XIFAXAN), which is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults, and is often used concomitantly with lactulose. The recommended dose of XIFAXAN for hepatic encephalopathy is one 550 mg tablet taken orally two times a day 2. Lactulose is also used for the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma, and has been shown to reduce blood ammonia levels and improve mental state in about 75% of patients 3.
- Key points:
- Rifaximin (XIFAXAN) is used to reduce the risk of overt hepatic encephalopathy (HE) recurrence in adults.
- Lactulose is used for the prevention and treatment of portal-systemic encephalopathy.
- The treatment is often used concomitantly with lactulose.
From the Research
Treatment for Hepatic Encephalopathy
The treatment for hepatic encephalopathy (HE) to prevent long-term dementia involves the use of non-absorbable disaccharides, such as lactulose, and antibiotics like rifaximin.
- Lactulose is effective in preventing overt HE recurrence over the long term 4
- The addition of rifaximin to lactulose significantly reduces the risk of overt HE recurrence and HE-related hospitalization, compared with lactulose therapy alone 4, 5, 6
- Combination therapy with rifaximin and lactulose has been shown to be more effective than lactulose alone in the treatment of overt HE, with a significant decrease in mortality and shorter hospital stay 5, 6
Patient-Reported Outcomes
Patient-reported outcomes (PROs) are also improved with the use of lactulose and rifaximin in HE patients.
- Lactulose has been shown to significantly improve overall patient-reported health-related quality of life, as well as several subscales 7
- Rifaximin has also demonstrated improvements in PROs, including overall health-related quality of life, social functioning, and sleep, although the evidence is not as strong as for lactulose 7
Long-Term Management
Long-term management of HE with lactulose and/or rifaximin is effective and safe, with studies showing that these treatments can be used for ≥6 months without compromising tolerability 4
- The use of lactulose and rifaximin in combination may result in substantial reductions in healthcare resource utilization over the long term, by reducing overt HE recurrence and associated rehospitalization 4