Increased availability of central benzodiazepine receptors in patients with chronic hepatic encephalopathy and alcohol related cirrhosis

Background/aims-To measure cerebral benzodiazepine receptor binding using C -11-flumazenil positron emission tomography in patients with stable chronic hepatic encephalopathy, who were also characterised by proton magnetic res onance spectroscopy. Methods-Six abstinent patients of mean age 61 years with alcohol related ci rrhosis and grade I-Ii hepatic encephalopathy and 11 matched healthy volunt eers were studied. Each patient's encephalopathy was defined according to c linical, psychometric, electroencephalographic, and magnetic resonance spec troscopy criteria. Using positron emission tomography, the brain volume of distribution of C-11-flumazenil was obtained; this reflects benzodiazepine receptor availability. Proton magnetic resonance spectra were acquired at 1 .5 T using a multivoxel technique; peak area ratios were calculated for cho line, glutamine/glutamate, N-acetyl-aspartate, and creatine resonances. Results-The mean volume of distribution of C-11-flumazenil was significantl y higher in the cortex, cerebellum, and the basal ganglia in the patients c ompared with controls (p<0.001). In the patient group, the mean glutamine/g lutamate to creatine ratio was significantly increased and the mean choline to creatine ratio was significantly decreased in all brain areas, compared with healthy volunteers. However, the N-acetylaspartate to creatine ratio was unchanged compared with controls. Conclusions-The spectroscopy results reflect the cerebral metabolic derange ment associated with hepatic encephalopathy. Stable grade I-II chronic hepa tic encephalopathy in alcohol related cirrhosis may be associated with incr eased cerebral benzodiazepine receptor availability. However, a direct effe ct of previous chronic exposure to alcohol cannot be excluded.