Hepatic Encephalopathy

BASICS

DESCRIPTION

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

EPIDEMIOLOGY

Male = female (reflects prevalence of underlying liver disease)

Incidence

  • 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%

Prevalence

  • May occur at any age; parallels the age predominance of fulminant liver disease: peaks in the 40s (Cirrhosis peaks in the late 50s.)
  • ~50% of patients with decompensated cirrhosis demonstrate features of HE (1)
  • Occurs in all cases of fulminant hepatic failure or acute liver failure (ALF).

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. Inflammation and gut dysbiosis have also been implicated in the disease pathophysiology.
  • Classifications based on 4 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: Covert to grades I–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: Non-precipitated or precipitated
  • 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.
  • Several metabolic factors are implicated in HE based on the failure of the liver to detoxify noxious CNS agents (e.g., ammonia, mercaptan, tyramine, fatty acids, lactate, manganese)
  • Ammonia is considered to act as a false neurotransmitter by inducing effects on inhibitory and excitatory neurotransmission through alteration of membrane potential.
  • Increased ammonia production leads to astrocyte swelling that can lead to fatal cerebral edema and death.

Genetics

  • 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.

RISK FACTORS

In patients with underlying liver disease, precipitating factors include:

  • 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 (e.g., asterixis, disorientation) and seek prompt treatment. Avoid nonessential medications, particularly opiates, benzodiazepines, and sedatives. Consider lactulose therapy as secondary prevention for recurrence of overt HE.
  • For patients who have already experienced bouts of overt HE while on lactulose monotherapy, lactulose + rifaximin is the best-documented agent to maintain remission (2).

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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