Hepatic Encephalopathy

Background

• Hepatic encephalopathy is a potentially reversible neuropsychiatric complication of liver failure with a wide variety of clinical manifestations from minimal changes in cognitive function to severe complications of stupor and coma.
• Hepatic encephalopathy usually occurs in patients with cirrhosis, but it can occur with other causes of portosystemic shunting or in acute liver failure, where it may develop with cerebral edema.

Evaluation

• Suspect onset of hepatic encephalopathy in patients with liver cirrhosis who have minimal changes in mental status, mood, or behavior. Common signs include unsteadiness and falls, poor sleep quality, fluctuating attention, and slow responses to requests.
• Patients may have typical signs of liver disease such as jaundice, ascites, and spider angiomata, in addition to mental status changes and neurologic manifestations of hepatic encephalopathy.
• Evaluate for precipitating factors such as fluid and electrolyte disturbances, particularly hyponatremia, hypokalemia, infections, dehydration, renal failure, gastrointestinal bleeding, inappropriate or unrecognized use of sedatives or recreational drugs, and constipation.
• Rule out other disorders that can alter brain function, such as intoxication, metabolic encephalopathy, and for people with recent falls or those found unconscious, intracranial hemorrhage, subdural hematoma, and/or head injury.
• Overt hepatic encephalopathy is diagnosed clinically after excluding other causes.
• Consider testing for minimal or covert hepatic encephalopathy with specialized neuropsychologic testing in patients for whom the presence of this complication may have strong implications on employment and/or public safety, for example as in motor vehicle licensure (Weak recommendation). When patients present with consistent symptoms, consider use of bedside testing such as the Stroop smartphone application test (also called EncephalApp) or Animal Naming test (ANT).

Management

• Identify and correct precipitating factors (such as infection, gastrointestinal bleeding, renal failure, electrolyte disturbances, sedative use) and consider other alternative causes of altered mental status (Strong recommendation).
• Perform an assessment of nutritional status, and evaluate suspected sarcopenia. Consider investigating micronutrient and vitamin deficiencies and treat as needed (Weak recommendation).
• Maintain nutrition with adequate protein intake and energy intake, with appropriate intake based on dry weight and level of malnourishment of:
  • for adults, based on ideal body weight, adjust protein intake to 1.2-1.5 g/kg/day and energy intake to 35-40 kcal/kg/day (Strong recommendation); consider adjusting energy intake to 20-40 kcal/kg/day according to patient body mass index (BMI) .
  • for children with cirrhosis, consider protein intake up to 4 g/kg/day based on ideal body weight
  • for patients with critical illness with cirrhosis, consider higher protein intake goals of 1.2-2 g/kg/day based on ideal body weight
• Use lactulose for treatment of episodic overt hepatic encephalopathy (Strong recommendation)
  • For inpatients, start with 30 mL orally every 1-2 hours until at least 2 bowel movements occur and then titrate to maintain 3-5 bowel movements per day until cognition improves. In the outpatient setting, same initial dose of lactulose can be started twice or 3 times daily and adjusted accordingly. Dosing recommendations have not been rigorously tested but dosing between 45 mL/day and 135 mL/day has been reported as therapeutic; higher doses may be associated with dehydration and hyponatremia or hypernatremia, paradoxically worsening hepatic encephalopathy.
  • In patients without oral route, consider placing a nasogastric tube to administer lactulose.
  • When a nasogastric tube cannot be safely placed, or in cases with high-grade (West Haven III or IV) overt hepatic encephalopathy needing a rapid response, start lactulose enemas (200 g or 300 mL of lactulose in 700 mL of water – retain for 30-60 min), then switch to oral route when able.
  • Continue oral lactulose for prevention of recurrent episodes, titrating dose to maintain 2-3 soft and comfortable stools per day; avoid diarrhea or loose stools.
• As an alternative to high-dose lactulose treatment consider initial lactulose dose followed by polyethylene glycol 3350 4 L orally or via nasogastric tube during a 4-hour period during the first day of hospital admission, then switch to oral lactulose on day 2.
• Use rifaximin 550 mg orally twice daily as add-on to lactulose for the prevention of recurrent episodes after second episode of hepatic encephalopathy (Strong recommendation).
• Evaluate patients with cirrhosis and hepatic encephalopathy for liver transplant (Strong recommendation).