What is the gamma-aminobutyric acid hypothesis of encephalopathy pathogenesis in cirrhosis?

Updated: Oct 15, 2020
  • Author: David C Wolf, MD, FACP, FACG, AGAF, FAASLD; Chief Editor: BS Anand, MD  more...
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GABA is a neuroinhibitory substance produced in the GI tract. It was postulated that GABA crosses the extrapermeable blood-brain barriers of patients with cirrhosis and then interacts with supersensitive postsynaptic GABA receptors. [40] This would lead to the generation of inhibitory postsynaptic potentials. Clinically, this interaction was believed to produce the symptoms of hepatic encephalopathy. Subsequent work has suggested that brain GABA levels are not increased in patients with cirrhosis.

However, brain levels of neurosteroids are increased in patients with cirrhosis. [41] They are capable of binding to their receptor within the neuronal GABA receptor complex and can increase inhibitory neurotransmission. Some investigators currently contend that neurosteroids may play a key role in hepatic encephalopathy. [42]

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