The aim of the study was to verify the role of yaminobutyric acid in the pathogenesis of hepatic encephalopathy occurring in cirrhotic patients by attempting to correlate plasma and cerebrospinal fluid content of authentic y-aminobutyric acid with the neurological manifestations of hepatic encephalopathy. For this purpose, plasma and cerebrospinal fluid y-aminobutyric acid levels were measured by means of mass fragmentography in 17 cirrhotic patients with hepatic encephalopathy and in 6 cirrhotics without neurological symtoms. Moreover, in all patients, a second sample was obtained during the clinical course of hepatic encephalopathy.
The mean plasma and cerebrospinal fluid y-aminobutyric acid levels were not different in patients with or without hepatic encephalopathy and did not change during the evolution of the neurological symptoms. The lack of changes in the y-aminobutyric acid content in plasma and cerebrospinal fluid during hepatic encephalopathy is in contrast with the hypothesized importance of increased entry into the brain of y-aminobutyric acid in the pathogenesis of hepatic encephalopathy.
In 1982, Schafer and Jones (1) developed the hypothesis which relates the inhibitory neurotransmitter y- aminobutyric acid (GABA) to hepatic encephalopathy (HE). According to these authors, in the course of liver failure, an increased amount of gut-derived GABA passes from the blood to the brain and contributes to the neural inhibition that characterizes HE. A number of experimental results supporting this hypothesis has been obtained in animals with galactosamine-induced fulminant hepatic failure and HE (2). Increased serum levels of GABA-like activity in patients with acute and chronic liver diseases have been determined by means of a radioreceptor method. The increment of plasma GABA-like activity was particularly evident in patients with acute gastrointestinal bleeding, irrespective of the presence of neurological impairment (3). The radioreceptor assay