What is the diagnosis for a patient with alcoholic cirrhosis, hyperammonemia, and periodic epileptiform discharges on electroencephalogram (EEG) with either diffuse cerebral edema?

From the Guidelines

The patient with alcoholic cirrhosis, severely elevated serum ammonia (324), and periodic epileptiform discharges on EEG with diffuse cerebral edema should be treated with lactulose 25-30mL every 1-2 hours until bowel movements occur, then 15-30mL 2-4 times daily to maintain 2-3 soft bowel movements per day, and rifaximin 550mg twice daily to reduce ammonia-producing gut bacteria, as recommended by the most recent guidelines 1. The treatment approach should prioritize lowering ammonia levels and managing cerebral edema.

• Lactulose is recommended as the primary treatment for hepatic encephalopathy, with a strong recommendation based on high-quality evidence 1.
• Rifaximin is recommended as an adjunct to lactulose for secondary prophylaxis following more than one episode of overt hepatic encephalopathy within 6 months, with a strong recommendation based on moderate-quality evidence 1.
• For cerebral edema, elevating the head of the bed to 30 degrees, considering mannitol 0.5-1g/kg IV if severe, and maintaining euvolemia are recommended, as these measures can help reduce intracranial pressure and improve cerebral perfusion.
• Avoiding sedatives and benzodiazepines, which can worsen encephalopathy, and correcting any electrolyte abnormalities, particularly potassium and sodium, are also crucial.
• Providing thiamine 500mg IV daily for 3-5 days to prevent Wernicke's encephalopathy is recommended, as thiamine deficiency is common in patients with alcoholic cirrhosis.
• Monitoring ammonia levels, neurological status, and EEG findings is essential to assess the response to treatment and adjust the management plan as needed. The most recent guidelines from the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) support this treatment approach, emphasizing the importance of prompt and aggressive management of hepatic encephalopathy to improve outcomes 1.

From the FDA Drug Label

The efficacy of XIFAXAN 550 mg taken orally two times a day was evaluated in a randomized, placebo-controlled, double-blind, multi-center 6-month trial of adult subjects from the U.S., Canada, and Russia who were defined as being in remission (Conn score of 0 or 1) from hepatic encephalopathy (HE). Breakthrough overt HE episodes were experienced by 31 of 140 subjects (22%) in the XIFAXAN group and by 73 of 159 subjects (46%) in the placebo group during the 6-month treatment period.

The patient has alcoholic cirrhosis with a serum ammonia level of 324 and periodic epileptiform discharges on EEG, either with diffuse edema.

• The use of rifaximin (XIFAXAN) may be beneficial in reducing the risk of hepatic encephalopathy (HE) breakthrough and HE-related hospitalizations in patients with a history of HE, as shown in the study 2.
• However, the specific scenario of alcoholic cirrhosis with elevated serum ammonia and periodic epileptiform discharges on EEG is not directly addressed in the provided drug label.
• Given the patient's condition, rifaximin (XIFAXAN) may be considered as part of the treatment plan, but the decision should be made with caution and under the guidance of a healthcare professional, taking into account the patient's overall clinical presentation and medical history.

From the Research

Alcoholic Cirrhosis and Hepatic Encephalopathy

• Alcoholic cirrhosis is a condition where the liver is damaged due to long-term alcohol consumption, leading to scarring and liver failure.
• Hepatic encephalopathy is a complication of cirrhosis, characterized by cognitive disturbances, ranging from mild confusion to coma, due to the accumulation of toxins in the blood.

Treatment of Hepatic Encephalopathy

• Lactulose is a commonly used treatment for hepatic encephalopathy, which works by reducing the production of ammonia in the gut and promoting the growth of beneficial gut bacteria 3.
• Rifaximin is an antibiotic that is also used to treat hepatic encephalopathy, and has been shown to be effective in combination with lactulose 4, 5, 6.
• The combination of rifaximin and lactulose has been shown to be more effective than lactulose alone in reducing the risk of overt hepatic encephalopathy recurrence and mortality 4, 5, 6.

Management of Elevated Serum Ammonia

• Elevated serum ammonia levels are a common feature of hepatic encephalopathy, and are associated with an increased risk of cognitive disturbances and mortality.
• Lactulose and rifaximin have been shown to be effective in reducing serum ammonia levels and improving cognitive function in patients with hepatic encephalopathy 4, 5, 6.

Periodic Epileptiform Discharges on EEG

• Periodic epileptiform discharges on EEG are a common feature of hepatic encephalopathy, and are associated with an increased risk of seizures and mortality.
• The treatment of periodic epileptiform discharges on EEG in patients with hepatic encephalopathy typically involves the use of anticonvulsant medications, in addition to treatments aimed at reducing serum ammonia levels and improving cognitive function.

Diffuse Edema

• Diffuse edema is a common feature of cirrhosis, and is associated with an increased risk of complications such as spontaneous bacterial peritonitis and hepatorenal syndrome.
• The treatment of diffuse edema in patients with cirrhosis typically involves the use of diuretics, in addition to treatments aimed at reducing serum ammonia levels and improving cognitive function.