THE RELATIONSHIP BETWEEN PLASMA AND BRAIN QUINOLINIC ACID LEVELS AND THE SEVERITY OF HEPATIC-ENCEPHALOPATHY

Background/Aims: Quinolinic acid is an endogenous neuroexcitant derive d from tryptophan. Brain quinolinic acid concentrations ave reportedly elevated in chronic liver failure. The aim of this study was to deter mine if brain quinolinic acid levels correlate with the severity of he patic encephalopathy. Methods: Postmortem samples of selected brain re gions and plasma samples taken at several stages of encephalopathy wer e obtained from patients with acute and chronic liver failure. Quinoli nic acid levels were measured by mass spectroscopy using [O-18]quinoli nic acid. Results: Plasma quinolinic acid levels were significantly in creased by stage I encephalopathy in patients with acute liver failure and by stages II and Ill in patients with chronic liver failure. Brai n quinolinic acid levels were elevated only in patients with acute liv er failure and were uniformly distributed at concentrations below thos e observed in plasma. Conclusions: The uniform distribution of quinoli nic acid at subplasma concentrations in the brains of patients with ac ute liver failure suggests that it is synthesized peripherally and ent ers the brain across a permeabilized blood-brain barrier. Whereas the elevation of brain quinolinic acid levels in patients who died of acut e but not chronic liver failure suggests that the involvement of quino linic acid in the pathogenesis of hepatic encephalopathy is minimal, i t could predispose these patients to seizures.