Marked Increases of Plasma Gamma-Aminobutyric Acid Concentrations in Cirrhotic Patients with Portacaval Shunts Are Not Associated with Alterations of Cerebral Functions

Abstract

Several previous studies have shown that the plasma concentration of γ-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.

Hepatische Enzephalopathie nach porto-systemischem shunt

“…Aufgrund unserer eigenen Ergebnisse und auch den Literaturangaben kann man davon ausgehen, dab die sch~idigenden Auswirkungen der Leberinsuffizienz von gr6gerer Bedeutung sind als die Folgen des porto-systemischen Shunts [18,19]. M~igige EEG-Verfinderungen wurden in 44% der Ffille gefunden, wobei diese elektrophysiologischen Anderungen mit einer Verschlechterung der Leberfunktion einhergingen.…”

“…Dieser Prozeg ftihrt zu erh6hten Konzentrationen von toxischen Ami-nos~iurederivaten, ver~inderten Transmitterprofilen und Rezeptor~inderungen [3,14]. In Tierexperimenten mit A n l a g e eines portosystemischen Shunts bei anniihernd normaler Leberfunktion bewirkte die Shunt-bedingte Erh6hung der A m m o n i a k s p i e g e l nur minimale Hirnstromver~inderungen ohne jegliche neurologische S y m p t o m a t i k [12,18,19]. Unabh~ingig von diesem Z u s a m m e n s p i e l ist es erwiesen, dab Patienten mit schlechter Leberfunktion durch eine exogene Stickstoffbelastung wesentlich mehr beeintrfichtigt werden als metabolisch gesunde Individuen.…”