• Acquired: liver failure results in shunting of blood from the liver to the inferior vena cava, decreased filtration of blood and removal of nitrogen-containing toxins by the liver, and then hyperammonemia.
  • Congenital: Defect in one of the enzymes of the urea cycle, which leads to lower production of urea from ammonia.


  • Primary
  • Secondary
    • Caused by inborn errors of intermediary metabolism (i.e. reduced activity of enzymes that are not part of the urea cycle)
    • Typically from acute or chronic liver failure

Clinical Features

  • AMS- ranging from mild apathy to frank coma
  • +/- asterexis
  • Signs/symptoms of underlying disease or trigger for exacerbation

Differential Diagnosis

Elevated ammonia level[1]

Altered mental status

Diffuse brain dysfunction

Primary CNS disease or trauma



  • Evaluate for suspected underlying etiology as above and/or alternate etiology of presenting symptoms (e.g. workup for other causes of AMS)
  • Normal range of ammonia in adult is typically 10-80 mcg/dL or 6-47 μmol/L, <100 in neonate, HOWEVER severity of hepatic encephalopathy is inconsistently correlated to severity of ammonia elevation[2]
    • Value of ammonia level in liver disease more helpful to trend rather than as absolute number


  • Treat underlying disorder
  • If hepatic encephalopathy:
    • Lactulose 20g PO or (300mL in 700cc H2O retention enema x30min)
      • In colon degrades into lactic acid: acidic environment traps ammonia
      • Also inhibits ammonia production in gut wall
  • If secondary to inborn error of metabolism
    • sodium phenylacetate/sodium benzoate (Ammonul) 250mg/kg in D10 over 90min; then 250mg/kg/d infusion
    • Arginine 210mg/kg IV/IO in D10 over 90min; then 210mg/kg/d infusion
    • +/- carnitine, 400 mg IV/IO in consultation w/specialist
    • May require dialysis if refractory/severe


  • Depends on cause

See Also

External Links


  1. Ferenci, P. Hepatic encephalopathy in adults: Clinical manifestations and diagnosis. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2020
  2. Ong JP, Aggarwal A, Krieger D, Easley KA, Karafa MT, Van Lente F, Arroliga AC, Mullen KD. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med. 2003 Feb 15;114(3):188-93. doi: 10.1016/s0002-9343(02)01477-8. PMID: 12637132.