PLASMA AND CSF BENZODIAZEPINE RECEPTOR-LIGAND CONCENTRATIONS IN CIRRHOTIC-PATIENTS WITH HEPATIC-ENCEPHALOPATHY - RELATIONSHIP TO SEVERITY OF ENCEPHALOPATHY AND TO PHARMACEUTICAL BENZODIAZEPINE INTAKE

Increased plasma and CSF concentrations of substances which bind to br ain benzodiazepine receptors have previously been reported in cirrhoti c patients with hepatic encephalopathy (HE). However, their relationsh ip to previous intake of pharmaceutical benzodiazepines has not been c learly established. In the present study, plasma levels of benzodiazep ine receptor ligands (BZRLs) were measured using a sensitive radiorece ptor assay in 12 control subjects with no evidence of hepatic, neurolo gical or psychiatric illness, 11 cirrhotic patients without HE, 24 cir rhotic patients with moderate (grade I-II) HE and in 45 cirrhotic pati ents with severe (grade II-IV) HE. In addition, CSF concentrations of BZRLs were measured in 8 cirrhotic patients with HE and an equal numbe r of age-matched controls. Recent intake (within 10 days) of pharmaceu tical benzodiazepines was assessed by detailed review of medical files , and interviews with the patient, at least one family member as well as the pharmacist. Significantly increased plasma concentrations of BZ RLs were observed in cirrhotic patients with severe encephalopathy (p< 0.02) compared to controls and to cirrhotic patients without (or with mild) neurological impairment. Increased plasma BZRLs could be account ed for by prior exposure to benzodiazepine medication in all cases. CS F concentrations of BZRLs in cirrhotic patients were not significantly different from control values. These findings do not support a role f or ''endogenous'' benzodiazepines in the pathogenesis of HE in chronic liver disease but suggest that pharmaceutic benzodiazepines administe red to cirrhotic patients as sedatives or as part of endoscopic work-u p could have contributed to the neurological impairment in some patien ts.