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For further information, see CMDT Part 16-11: Cirrhosis

Key Features

Essentials of Diagnosis

  • Stage 1: mild confusion

  • Stage 2: drowsiness

  • Stage 3: stupor

  • Stage 4: coma

  • A revised staging system known as SONIC (Spectrum Of Neurocognitive Impairment in Cirrhosis) encompasses absent, covert, and stages 2 to 4 encephalopathy

General Considerations

  • A state of disordered central nervous system function resulting from failure of the liver to detoxify noxious agents of gut origin because of hepatocellular dysfunction and portosystemic shunting

  • Ammonia is the most readily identified toxin but is not solely responsible for the disturbed mental status

  • Precipitants of hepatic encephalopathy

    • Gastrointestinal (GI) bleeding—increases the protein in the bowel and rapidly precipitates hepatic encephalopathy

    • Constipation

    • Alkalosis

    • Potassium deficiency induced by diuretics

    • Opioids, hypnotics, and sedatives

    • Medications containing ammonium or amino compounds

    • Paracentesis with consequent hypovolemia

    • Hepatic or systemic infection

    • Portosystemic shunts (including transjugular intrahepatic portosystemic shunts)

  • In one study, risk factors for hepatic encephalopathy in patients with cirrhosis included a higher serum bilirubin level and use of a nonselective β-blocker, whereas a higher serum albumin level and use of a statin were protective


  • Alcoholic liver disease and chronic hepatitis C are the most common etiologies of cirrhosis

Clinical Findings

Symptoms and Signs

  • Metabolic encephalopathy characterized by

    • Day–night reversal

    • Asterixis, tremor, dysarthria

    • Delirium

    • Drowsiness, stupor, and ultimately coma

  • In patients with cirrhosis, may be precipitated by an acute hepatocellular insult or an episode of GI bleeding

  • Clinical diagnosis supported by asterixis, elevated serum ammonia with exclusion of other causes of delirium

  • Covert hepatic encephalopathy is characterized by mild cognitive and psychomotor deficits

    • EncephalApp

      • A smartphone app that uses the "Stroop test" (asking the patient to name the color of a written word rather than the word itself, even when the word is the name of a different color)

      • Has proved useful for detecting covert hepatic encephalopathy

Differential Diagnosis

  • Metabolic encephalopathy, especially hyponatremia, hypoglycemia, or chronic kidney disease

  • CNS infection

  • Altered mental status from medication effects, particularly if they are hepatically metabolized


Laboratory Tests

  • Liver biochemical tests often consistent with advanced chronic liver disease

  • Serum (and cerebrospinal fluid) ammonia level is generally elevated

  • Role of neuroimaging tests (eg, cerebral positron emission tomography, magnetic resonance spectroscopy) is evolving



  • Purge blood from the GI tract with 120 mL of magnesium citrate by mouth or nasogastric (NG) tube every 3–4 hours until the stool is free of gross blood, or by administration of lactulose

  • Lactulose

    • Initial dose is 30 mL three or four times daily orally

    • Titrate so that the patient produces two or ...

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