From the Guidelines
Elevated ammonia levels are a common complication in cirrhosis patients, and managing them is crucial to prevent hepatic encephalopathy, with lactulose being the first-line treatment, as recommended by the most recent guidelines 1. To reduce high ammonia levels in cirrhosis patients, the following measures are recommended:
- Lactulose is typically started at 25-30 mL orally two to three times daily, with the dose adjusted to achieve 2-3 soft bowel movements per day.
- Rifaximin 550 mg twice daily is often added as an adjunct therapy, particularly for patients with recurrent hepatic encephalopathy.
- Other supportive measures include:
- Limiting dietary protein to 1-1.5 g/kg/day
- Avoiding constipation
- Treating infections promptly
- Avoiding medications that can worsen encephalopathy such as sedatives and diuretics Ammonia builds up in cirrhosis because portal hypertension causes blood to bypass the liver through collateral vessels, and damaged hepatocytes have reduced capacity to metabolize ammonia in the urea cycle, as explained in the French recommendations for the diagnosis and management of hepatic encephalopathy 1. The relationship between malnutrition and hepatic encephalopathy has been known, and human studies support this association, with muscle playing an important role in ammonia removal, as discussed in the EASL clinical practice guidelines on nutrition in chronic liver disease 1. Regular monitoring of mental status and ammonia levels is essential for managing these patients effectively, and the EASL clinical practice guidelines on the management of hepatic encephalopathy provide recommendations for the prevention and treatment of hepatic encephalopathy in patients with cirrhosis 1.
From the Research
Ammonia Levels in Cirrhosis
- Ammonia is a major neurotoxin implicated in the pathogenesis, progression, and severity of hepatic encephalopathy (HE) in patients with cirrhosis 2.
- Patients with cirrhosis exhibit decreased ammonia clearance and increased ammonia production compared to healthy persons 3.
- The relative roles of reduced ammonia clearance and increased ammonia production are poorly understood, as is the action of ammonia-targeting treatments 3.
Therapies for Reducing Ammonia Levels
- Various anti-ammonia therapies with synergistic and complementary actions have been attempted for overt HE and for prophylaxis of the first and recurrent episodes of HE 2.
- Rifaximin and lactulose have been reported to be effective for maintenance of remission from HE in patients with cirrhosis 4, 5.
- Combination of lactulose plus rifaximin is more effective than lactulose alone in the treatment of overt HE 5.
- Phenylbutyrate increases ammonia clearance, whereas lactulose + rifaximin reduces production 3.
Clinical Management of Hepatic Encephalopathy
- Ammonia levels do not guide clinical management of patients with HE caused by cirrhosis 6.
- Inpatient management of HE with lactulose was not influenced by either the presence or level of ammonia level 6.
- The average lactulose dose in patients with an elevated ammonia level was identical to the lactulose dose in patients with a normal ammonia level 6.