What is the diagnosis and treatment for Hepatic (Liver) Encephalopathy?

From the Guidelines

Hepatic encephalopathy should be managed with lactulose as the primary treatment, and rifaximin should be added for secondary prophylaxis in patients with recurrent episodes, as recommended by the most recent guidelines 1. The mainstay of treatment for hepatic encephalopathy is lactulose, a non-absorbable disaccharide, given at a dose of 25-30 mL orally every 1-2 hours until bowel movements occur, then adjusted to 15-30 mL 2-3 times daily to maintain 2-3 soft bowel movements per day.

• Key aspects of management include:
  • Identifying and treating precipitating factors such as gastrointestinal bleeding, infection, electrolyte disturbances, or medication non-compliance
  • Maintaining adequate protein intake (1.2-1.5 g/kg/day) with emphasis on vegetable and dairy protein sources, as protein restriction is no longer routinely recommended
  • Considering airway protection for patients with severe encephalopathy
  • Regular monitoring of liver function and consideration for liver transplantation evaluation in appropriate candidates
• The pathophysiology of hepatic encephalopathy involves impaired liver function leading to decreased clearance of ammonia and other neurotoxins, which cross the blood-brain barrier and disrupt neurotransmission, particularly affecting astrocyte function 1.
• Recent guidelines suggest that rifaximin, a non-absorbable antibiotic, can be added at 550 mg twice daily for patients with recurrent episodes, and that lactulose and rifaximin can be used for secondary prophylaxis 1.
• It is essential to note that the diagnosis of hepatic encephalopathy should be based on the West Haven criteria, and that alternative or additional causes of neuropsychiatric impairment should be identified to improve prognostic accuracy and treatment outcomes 1.

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. Neomycin sulfate has been shown to be effective adjunctive therapy in hepatic coma by reduction of the ammonia-forming bacteria in the intestinal tract.

Hepatic Encephalopathy Treatment Options:

• Lactulose solution therapy reduces blood ammonia levels and improves mental state and EEG patterns in about 75% of patients 2.
• Rifaximin is indicated for reduction in risk of overt hepatic encephalopathy recurrence in adults, often used concomitantly with lactulose 3.
• Neomycin sulfate is effective as adjunctive therapy in hepatic coma by reducing ammonia-forming bacteria in the intestinal tract 4.

From the Research

Hepatic Encephalopathy Treatment

• Hepatic encephalopathy (HE) is a broad spectrum of neuropsychiatric manifestations usually affecting individuals with end-stage liver disease 5.
• The mainstay of treatment for HE is nonabsorbable disaccharides, particularly lactulose, which has been shown to be effective in reducing blood ammonia levels 5.
• Alternative treatments for HE include zinc, antibiotics (neomycin, metronidazole, and rifaximin), ornithine aspartate, sodium benzoate, probiotics, and surgical intervention 5.
• Combination therapy with rifaximin and lactulose has been shown to be more effective than lactulose alone in the treatment of overt HE, with a significant decrease in mortality and hospital stay 6, 7, 8.

Efficacy of Rifaximin and Lactulose Combination

• A systematic review and meta-analysis of randomized controlled trials found that the use of rifaximin plus lactulose was associated with an increased incidence of effective rate and reduced risk of mortality compared to lactulose alone 7.
• Another study found that the addition of rifaximin to lactulose significantly reduced the risk of overt HE recurrence and HE-related hospitalization, compared with lactulose therapy alone, without compromising tolerability 8.
• The combination of lactulose and rifaximin has been shown to be effective in the long-term management of HE, with substantial reductions in healthcare resource utilization over the long term 8.

Diagnosis and Precipitating Causes

• The diagnosis of overt HE should include a careful search for predisposing factors, including underlying infection, gastrointestinal bleeding, electrolyte disturbances, hepatocellular carcinoma, dehydration, hypotension, and excessive use of benzodiazepines, psychoactive drugs, or alcohol 5, 9.
• Once the diagnosis of overt HE is made, every effort to identify and correct the precipitating cause is essential for the resolution of symptoms 9.