Hepatic Encephalopathy



  • Reversible altered mental and neuromotor functioning in association with acute or chronic liver disease and/or portosystemic shunting
  • Wide spectrum of neurologic/psychiatric abnormalities ranging from subclinical alterations to coma: Prominent features are confusion, impaired arousability, and a “flapping tremor” (asterixis).


Male = female (reflects prevalence of underlying liver disease)


  • The risk of first episode of overt hepatic encephalopathy (HE) is 5–25% within 5 years of cirrhosis diagnosis.
  • Posttransjugular intrahepatic portosystemic shunt (TIPS), median cumulative 1-year incidence of overt HE is 10–50%


  • May occur at any age; parallels the age predominance of fulminant liver disease: peaks in the 40s (Cirrhosis peaks in the late 50s.)
  • Occurs in all cases of fulminant hepatic failure or acute liver failure (ALF); overt HE occurs in 30–45% of cirrhotic patients; present in ~50% of patients requiring liver transplantation

Etiology and Pathophysiology

  • There is no defined pathophysiology for the development of HE. However, elevated serum levels of ammonia (hyperammonemia) correlate with the severity of HE, suggesting a central role of ammonia as a neurotoxin.
  • Classifications based on four factors have been proposed:
    • According to the underlying disease:
      • Type A: resulting from ALF; type B: resulting from portosystemic bypass or shunting in absence of inherent liver disease; type C: resulting from cirrhosis
    • According to severity of manifestation:
      • West Haven classification: Convert to grades I to IV (see “Physical Exam” section).
    • According to time course:
      • Episodic HE; recurrent HE = >1 episode occurring within 6 months; persistent HE = persistent behavioral alterations interspersed with relapses of overt HE
    • According to precipitating factors:
      • Nonprecipitated; precipitated
  • Several metabolic factors implicated in HE based on the failure of the liver to detoxify noxious CNS agents (e.g., ammonia, mercaptan, octopamine, tyramine, fatty acids, lactate, manganese)
  • Increased aromatic and reduced branched chain amino acids in blood may act as false neurotransmitters, possibly interacting with the γ-aminobutyric acid (GABA) receptor to cause clinical symptoms
  • HE presents most commonly in patients with long-standing cirrhosis and spontaneous shunting of intestinal blood through collateral vessels or surgical portacaval shunts.
  • Asterixis is the inability to maintain a particular posture due to metabolic encephalopathy. Abnormal diencephalic function leads to the characteristic liver flap noted when the arms and wrists are held in extension.


  • Unknown/unclear
  • Conditions that predispose an individual to developing chronic liver disease such as cystic fibrosis, α1-antitrypsin deficiency, hemochromatosis, and Wilson disease can contribute to the development of HE.
  • A glutaminase gene variation that increases enzyme activity may predispose patients to develop HE.

Risk Factors

In patients with underlying liver disease, precipitating factors include the following:

  • Electrolyte disturbance (Na+, K+, Mg2+ most common); infection (overt or occult, including spontaneous bacterial peritonitis [SBP]); GI hemorrhage
  • Use of sedative (e.g., benzodiazepines) or opiate drugs; fluid abnormalities including from diuretic overuse
  • TIPS—a radiologically inserted shunt to lower portal pressure—elderly patients and those with worse liver function are at increased risk of developing HE following TIPS.

General Prevention

  • Recognize early signs and seek prompt treatment. Avoid nonessential medications, particularly opiates, benzodiazepines, and sedatives. Consider lactulose therapy as secondary prophylaxis for recurrence of overt HE.
  • For patients who have already experienced bouts of overt HE while on lactulose, lactulose + rifaximin is the best-documented agent to maintain remission (1).

Commonly Associated Conditions

  • Cirrhosis; portal hypertension; may occur as a complication of acute fatty liver of pregnancy
  • Occurs rarely in patients with a portacaval shunt accompanied by normal liver function

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