From the Guidelines
When lactulose and rifaximin fail to control hepatic encephalopathy, oral BCAA is a viable third-line treatment option, administered at a dose of 0.25 g/kg/day. This recommendation is based on the most recent and highest quality study available, which suggests that oral BCAA can be used additionally to manage hepatic encephalopathy 1. Other alternatives, such as intravenous L-ornithine-L-aspartate (LOLA) or albumin, can also be considered, but the evidence supporting their use is not as strong as that for oral BCAA.
Key Considerations
- The primary goal of treatment is to reduce ammonia production and improve its clearance from the bloodstream.
- Precipitating factors, such as infections, gastrointestinal bleeding, or electrolyte disturbances, should be addressed and managed concurrently with third-line treatment.
- Protein restriction should be maintained as appropriate for the patient's condition.
- Regular monitoring of ammonia levels, mental status, and potential medication side effects is crucial for optimal management.
Treatment Options
- 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
It is essential to note that liver transplantation may be indicated in patients with severe hepatic encephalopathy who do not respond to medical treatments, as recommended by the guidelines 1. Additionally, nutritional aspects, such as providing enough protein and energy to favor a positive nitrogen balance and increase in muscle mass, should be prioritized to prevent worsening of hepatic encephalopathy 1.
From the Research
Third Line Treatment Options for Hepatic Encephalopathy
When first and second line agents, such as lactulose and rifaximin, are not effective, the following options may be considered:
- Zinc, antibiotics (neomycin, metronidazole), ornithine aspartate, sodium benzoate, probiotics, and surgical intervention may be used as alternative treatments 2
- Newer therapies, including manganese chelators, L-carnitine, N-methyl-d-aspartate receptor antagonists, blood purification dialysis system, and an intravenous combination of sodium benzoate and phenylacetate, are still in development and awaiting human trials 2
- Polyethylene glycol, albumin, branched-chain amino acids, probiotics and fecal microbiota transplant, zinc, and l-ornithine-l-aspartate may be considered as newer, second-line therapies 3
Key Considerations
- The mainstay of treatment for hepatic encephalopathy has been nonabsorbable disaccharides, particularly lactulose, with rifaximin being used as a second-line agent 4, 5
- The use of antibiotics, such as neomycin, metronidazole, and rifaximin, has been shown to be effective in reducing bacterial production of ammonia and improving symptoms of hepatic encephalopathy 4, 6
- The choice of third-line treatment option should be based on individual patient needs and circumstances, and may involve a combination of therapies 2, 3