How to manage liver failure with low ammonia levels?

From the Guidelines

Managing liver failure with low ammonia levels requires a comprehensive approach focusing on treating the underlying cause while preserving remaining liver function, with medications typically including lactulose and rifaximin to prevent hepatic encephalopathy, as suggested by the most recent guidelines 1.

Key Considerations

• Identify and address the specific etiology of liver failure, which may include viral hepatitis, alcoholic liver disease, drug-induced liver injury, or autoimmune hepatitis.
• Nutritional support is crucial, with a balanced protein intake of 1.0-1.5 g/kg/day to prevent muscle wasting without overloading the liver.
• Medications such as lactulose (15-30 ml orally 2-4 times daily, titrated to produce 2-3 soft bowel movements daily) and rifaximin (550 mg twice daily) are recommended to prevent hepatic encephalopathy, even with currently low ammonia levels, as per the guidelines 1.
• Diuretics such as spironolactone (starting at 100 mg daily) and furosemide (starting at 40 mg daily) help manage ascites and fluid retention.

Monitoring and Prevention

• Regular monitoring of liver function tests, coagulation parameters, electrolytes, and ammonia levels is essential, with testing frequency determined by disease severity.
• Avoid hepatotoxic medications and alcohol completely.
• Even with normal ammonia levels, patients should be monitored for subtle signs of encephalopathy such as sleep disturbances, mild confusion, or decreased concentration, as suggested by the guidelines 1.

Treatment Approach

• The use of nonabsorbable disaccharides, such as lactulose, is recommended in critically ill ACLF patients with overt hepatic encephalopathy, as per the guidelines 1.
• Rifaximin is suggested as an adjunctive therapy in critically ill ACLF patients with overt hepatic encephalopathy, as per the guidelines 1.
• Enteral polyethylene glycol may be used as an alternative to lactulose in critically ill ACLF patients with overt hepatic encephalopathy, as suggested by the guidelines 1.

From the FDA Drug Label

Lactulose causes a decrease in blood ammonia concentration and reduces the degree of portal-systemic encephalopathy. Controlled studies have shown that lactulose solution therapy reduces the blood ammonia levels by 25 to 50%; this is generally paralleled by the improvement in the patients’ mental state and by an improvement in EEG patterns.

Management of Liver Failure with Low Ammonia Levels:

• The use of lactulose may still be beneficial in managing liver failure, even with low ammonia levels, as it can help reduce the degree of portal-systemic encephalopathy and improve the patient's mental state 2, 2.
• Lactulose therapy has been shown to improve protein tolerance and EEG patterns in patients with portal-systemic encephalopathy, which may be beneficial in managing liver failure 2.
• However, the primary goal of treatment should be to address the underlying cause of liver failure and manage its complications, rather than solely focusing on ammonia levels.

From the Research

Management of Liver Failure with Low Ammonia Levels

• The management of liver failure with low ammonia levels is a complex process that requires a comprehensive approach, considering the underlying cause of liver failure and the patient's overall health status 3.
• Branched-chain amino acids (BCAAs) have been shown to have a positive effect on ammonia detoxification and may be beneficial in the treatment of liver failure, even in patients with low ammonia levels 3.
• However, BCAA supplementation may also lead to enhanced ammonia production from glutamine breakdown in the intestine and kidneys, which could exacerbate hepatic encephalopathy 3.
• The use of lactulose and rifaximin has been shown to be effective in the treatment of hepatic encephalopathy, and may be beneficial in patients with liver failure and low ammonia levels 4, 5.
• Ammonia levels have been shown to be a predictor of mortality in patients with acute liver failure, and elevated ammonia levels are associated with a higher risk of mortality 6, 7.
• The management of liver failure with low ammonia levels should be individualized and based on the patient's specific needs and health status, taking into account the potential benefits and risks of different treatment options 3, 4, 5.

Treatment Options

• BCAAs: may be beneficial in the treatment of liver failure, but may also lead to enhanced ammonia production 3.
• Lactulose and rifaximin: have been shown to be effective in the treatment of hepatic encephalopathy, and may be beneficial in patients with liver failure and low ammonia levels 4, 5.
• α-ketoglutarate and phenylbutyrate: may be used in combination with BCAAs to inhibit glutamine breakdown and enhance glutamine excretion, respectively 3.

Monitoring and Follow-up

• Ammonia levels: should be monitored regularly to assess the effectiveness of treatment and predict mortality risk 6, 7.
• Liver function: should be monitored regularly to assess the progression of liver disease and the effectiveness of treatment.
• Overall health status: should be monitored regularly to assess the patient's response to treatment and identify any potential complications or side effects.