Marked increases of plasma gamma-aminobutyric acid concentrations in cirrhotic patients with portacaval shunts are not associated with alterations of cerebral functions.
Several previous studies have shown that the plasma concentration of gamma-amino-butyric acid (GABA) is markedly increased in patients with hepatic encephalopathy, and it has been suggested that decreased metabolism of peripheral GABA might contribute to the cerebral dysfunctions observed. In the present study, plasma GABA-like activity was determined by a radioreceptor assay in 21 cirrhotic patients in whom, at least 2 months prior to the study, portocaval shunt surgery had been performed for treatment of recurrent variceal bleeding. Compared to 10 healthy volunteers, plasma GABA concentrations were increased in all cirrhotic patients, whereas most other amino acids, including those known to interfere with the GABA radioreceptor assay at elevated concentrations, were within the normal range. Despite an about 3- to 16-fold increase in individual GABA concentration, none of the patients showed clinical signs of overt hepatic encephalopathy on conventional neurologic (including EEG) and mental status examination. Furthermore, when a psychometric test system was used for evaluation of intellectual and psychomotor functions, all patients performed within the normal range and could not be distinguished from healthy volunteers. The data indicate that, at least in chronic liver disease, impaired metabolism of peripheral GABA does not lead to cerebral dysfunctions.