Common precipitating factors in hepatic encephalopathy

The primary factor associated with an increased risk of hepatic encephalopathy (HE) is increased serum and brain ammonia.

Increased ammonia production may occur due to:1

  • High protein load diet
  • Gastrointestinal bleeding
  • Hypokalemia
  • Metabolic alkalosis
  • Constipation
  • Infection
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Volume deficiency is another precipitating factor and diuretics (in forced mobilisation of ascites), vomiting, diarrhoea and bleeding can all influence this.1 Other precipitating factors include drugs, transjugular intrahepatic portosystemic stent shunt (TIPS) and hypoxia.1

Additional synergistic factors may also play a role in the pathogenesis of HE, including cerebral hyperaemia, intracranial hypertension (acute liver failure),2 inflammation, infection, ammonia-induced mitochondrial dysfunction-energy impairment, reactive oxygen species (ROS) production, oxidative/nitrosative stress-modification of proteins (ex. tyrosine nitration) altering cellular function and NMDA-receptor activation.2-4


1. Zhan T, Stremmel W. The diagnosis and treatment of minimal hepatic encephalopathy. Dtsch Arztebl Int 2012;109(10):180-7.
2. Shawcross DL et al. Ammonia and hepatic encephalopathy: the more things change, the more they remain the same. Metab Brain Dis 2005;20(3):169-79.
3. Wright G, Jalan R. Management of hepatic encephalopathy in patients with cirrhosis. Best Pract Res Clin Gastroenterol. 2007;21(1):95-110.
4. Butterworth RF. Neuronal cell death in hepatic encephalopathy. Metab Brain Dis 2007;22(3-4):309-20.