From the Guidelines
Hepatic encephalopathy should be treated with lactulose as the first-line medication, with a dose of 30-45 mL orally every 1-2 hours until the patient is having at least 2 bowel movements a day, as recommended by the most recent guidelines 1.
Treatment Overview
The treatment of hepatic encephalopathy focuses on reducing ammonia levels in the blood.
- Lactulose is the primary medication used, with a recommended dose of 30-45 mL orally every 1-2 hours until the patient is having at least 2 bowel movements a day.
- The dose should then be titrated to achieve two to three soft stools per day.
- Rifaximin, a non-absorbable antibiotic, can be added to reduce ammonia-producing gut bacteria, especially in patients with recurrent episodes of hepatic encephalopathy 1.
Precipitating Factors
Identifying and treating precipitating factors such as:
- Infections
- Gastrointestinal bleeding
- Electrolyte disturbances
- Medication non-compliance is crucial in managing acute episodes of hepatic encephalopathy 1.
Protein Intake
Patients with hepatic encephalopathy should maintain adequate protein intake, with an emphasis on vegetable and dairy protein sources, rather than restricting protein intake 1.
Long-term Management
Long-term management includes lactulose and rifaximin to prevent recurrence, especially in patients with previous episodes of hepatic encephalopathy 1.
Monitoring and Prevention
Regular monitoring of mental status, medication adherence, and avoidance of sedatives and alcohol are essential components of ongoing management. Patients with recurrent or persistent hepatic encephalopathy should be considered for liver transplantation, and a first episode of overt hepatic encephalopathy should prompt referral to a transplant center for evaluation 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.
Hepatic Encephalopathy Treatment Options:
- Lactulose is used for the prevention and treatment of portal-systemic encephalopathy, including hepatic pre-coma and coma 2.
- Rifaximin is used for the 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, but most patients were also using lactulose concomitantly 3.
From the Research
Definition and Pathophysiology of Hepatic Encephalopathy
- Hepatic encephalopathy (HE) is a broad spectrum of neuropsychiatric manifestations usually affecting individuals with end-stage liver disease 4.
- The presence of HE is a poor prognostic sign, with 1-year mortality rates of almost 60% 4.
- Elevated plasma and central nervous system ammonia levels are considered key factors in its pathogenesis 4.
Treatment of Hepatic Encephalopathy
- The mainstay of treatment for many years has been nonabsorbable disaccharides, particularly lactulose 4.
- Alternative treatments, which usually are second line in patients who do not respond to lactulose, include zinc, antibiotics (neomycin, metronidazole, and rifaximin), ornithine aspartate, sodium benzoate, probiotics, and surgical intervention 4.
- Combination of lactulose plus rifaximin is more effective than lactulose alone in the treatment of overt HE 5.
- Lactulose is effective for the prevention of overt HE recurrence over the long term and the addition of rifaximin to lactulose significantly reduces the risk of overt HE recurrence and HE-related hospitalization 6.
Comparison of Treatment Outcomes
- A study comparing the efficacy of a combination of rifaximin and lactulose with lactulose only in the treatment of overt HE found that the patients who were on lactulose and placebo revealed to have lower mortality than those on lactulose and rifaximin 7.
- However, another study found that there was a significant decrease in mortality after treatment with lactulose plus rifaximin vs. lactulose and placebo 5.
- The addition of rifaximin to standard lactulose therapy may result in substantial reductions in healthcare resource utilization over the long term, by reducing overt HE recurrence and associated rehospitalization 6.
Long-term Management of Hepatic Encephalopathy
- Long-term effectiveness outcomes were reported in eight articles for treatment with lactulose alone and 19 articles for treatment with rifaximin, alone or in combination with lactulose 6.
- Long-term safety/tolerability outcomes were reported in six articles for treatment with lactulose alone and nine articles for treatment with rifaximin, alone or in combination with lactulose 6.
- Current evidence supports recommendations for the use of lactulose therapy for the prevention of overt HE recurrence over the long term, and for the additional benefit of adding rifaximin to lactulose therapy 6.