From the Guidelines
The treatment for hepatic encephalopathy primarily focuses on reducing ammonia levels in the blood, with lactulose as the first-line medication, typically started at 20-30 g orally 3-4 times per day, and adjusted to achieve 2-3 soft stools per day, as recommended by the most recent guidelines 1. The goal of treatment is to reduce ammonia levels, and lactulose works by acidifying the colon, trapping ammonia, and facilitating its excretion.
- Key treatment options include:
- Lactulose: 20-30 g orally 3-4 times per day, adjusted to achieve 2-3 soft stools per day
- Rifaximin: 400 mg three times/day or 550 mg twice/day, often added to reduce ammonia-producing gut bacteria and prevent recurrence
- Oral BCAA: 0.25 g/kg/day
- Intravenous LOLA: 30 g/day
- Albumin: 1.5 g/kg/day until clinical improvement or for 10 days, maximum
- For patients who cannot take oral medications, lactulose can be administered as an enema (200 g in 700 mL water) 3-4 times per day in severe cases.
- Precipitating factors such as gastrointestinal bleeding, infection, electrolyte disturbances, or medication non-compliance must be identified and addressed.
- In severe cases, patients may require intensive care support, including intubation for airway protection.
- Patients should be educated about medication adherence, avoiding sedatives and alcohol, and recognizing early signs of recurrence to prevent hospitalization, as suggested by the French recommendations 1. The most recent and highest quality study 1 provides strong agreement for the use of lactulose as the first-line treatment, and suggests the addition of rifaximin to prevent recurrence of hepatic encephalopathy in cases of failed prevention with lactulose.
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.
The treatment options for hepatic (liver) encephalopathy are:
- Lactulose (PO): for the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma 2
- Rifaximin (PO): for reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults, often used concomitantly with lactulose 3
From the Research
Treatment Options for Hepatic Encephalopathy
The treatment options for hepatic encephalopathy include:
- Nonabsorbable disaccharides, such as lactulose, which is considered the first-line therapeutic agent for treating hepatic encephalopathy 4, 5, 6
- Systemic antibiotics, primarily neomycin, although their use is limited due to associated adverse events 4
- Semisynthetic, nonsystemic antibiotics, such as rifaximin, which has been shown to be effective in improving behavioral, laboratory, mental, and intellectual abnormalities in patients with hepatic encephalopathy 4, 5
- Branch chain amino acids, which are beneficial in subjects who are protein intolerant 5
- L-ornithine L-aspartate and probiotics, which are also useful in the management of hepatic encephalopathy 5, 6
- Combination therapy of disaccharides with rifaximin, L-ornithine L-aspartate, or probiotics, although further validation is needed in large studies 6
- Newer therapeutic targets under evaluation, including ammonia scavengers and modulation of gut microbiota, such as fecal microbiota transplantation 7
Therapeutic Agents and Their Mechanisms
The therapeutic agents used to manage hepatic encephalopathy work by:
- Lowering the gut nitrogen load and thus the serum ammonia level 8
- Acidifying the gastrointestinal tract to inhibit production of ammonia by coliform bacteria 4
- Altering gastrointestinal flora to decrease intestinal production and absorption of ammonia 4
- Providing nutritional support and stabilizing the patient 8
Management Strategies
The management of hepatic encephalopathy involves:
- Identifying and treating precipitating factors 5, 8
- Providing supportive care and stabilization, including appropriate nutritional support 8
- Using therapeutic agents to lower the gut nitrogen load and thus the serum ammonia level 8
- Considering large portosystemic shunts embolization and liver transplant in certain groups of patients 5