The relationship between plasma and brain quinolinic acid levels and the severity of hepatic encephalopathy

Background/Aims: Quinolinic acid is an endogenous neuroexcitant derived from tryptophan. Brain quinolinic acid concentrations are reportedly elevated in chronic liver failure. The aim of this study was to determine if brain quinolinic acid levels correlate with the severity of hepatic encephalopathy. Methods: Postmortem samples of selected brain regions and plasma samples taken at several stages of encephalopathy were obtained from patients with acute and chronic liver failure. Quinolinic acid levels were measured by mass spectroscopy using [¹⁸O]quinolinic acid. Results: Plasma quinolinic acid levels were significantly increased by stage I encephalopathy in patients with acute liver failure and by stages II and III in patients with chronic liver failure. Brain quinolinic acid levels were elevated only in patients with acute liver failure and were uniformly distributed at concentrations below those observed in plasma. Conclusions: The uniform distribution of quinolinic acid at subplasma concentrations in the brains of patients with acute liver failure suggests that it is synthesized peripherally and enters the brain across a permeabilized blood-brain barrier. Whereas the elevation of brain quinolinic acid levels in patients who died of acute but not chronic liver failure suggests that the involvement of quinolinic acid in the pathogenesis of hepatic encephalopathy is minimal, it could predispose these patients to seizures.