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Hepatic encephalopathy (HE)

  • Neuropsychiatric syndrome caused by liver disease
  • Confusion is followed by coma as disease progresses

Etiology

  • Precipitating factors (see box)

Pathophysiology

  • Disturbance of brain function provoked by circulating neurotoxins that are normally metabolised by the liver
  • Most pts have evidence of liver failure and portosystemic shunting of blood
  • Neurotoxins causing encephalopathy are unknown
    • Thought to be nitrogenous substances produced in the gut by bacteria
    • Normally metabolised by the healthy liver and excluded from the systemic circulation
    • Potential compounds
      • Ammonia
      • GABA
  • The brain in cirrhosis can also be sensitised to other factors (drugs etc) – that can precipitate condition
  • Disruption of blood brain barrier is a feature of acute hepatic failure – can lead to Cerebral oedema

Clinical features

  • Changes of intellect, personality, emotions and consciousness ± neurological signs
  • Degree of encephalopathy can be added from 1-4
  • Early features are mild
  • Apathy, inability to concentrate, confusion, disorientation, drowsiness, slurring of speech, eventually coma
  • Convulsions
  • Flapping tremor (asterixis)
  • Inability to perform simple mental maths or draw objects
  • As condition progresses – hyperreflexia
  • Fetor hepaticus – sweet musty odour on breath
    • More a sign of liver failure and portosystemic shunting
  • Chronic HE can cause cerebellar dysfunction
    • Parkinsonian syndromes, spastic paraplegia and dementia

Investigations

  • Diagnosis made clinically, EEG when in doubt
    • Shows diffuse slowing of the normal alpha waves, with eventual development of delta waves
  • Increased arterial ammonia

Management

  • Treat/remove precipitating causes
  • Suppress production of neurotoxins by bacteria in the bowel (regular enema)
  • Lactulose – 15-30ml tid
    • Reduces pH of colonic content, so limits colonic ammonia absorption and promotes incorporation of nitrogen into bacteria
  • Rifaximin – 400mg tid
    • Well tolerated AB, reduces bacterial content of bowel
  • Chronic/refractory HE – one of the main indications for liver transplantation
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