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)

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.

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