title: Plasma and CSF benzodiazepine receptor ligand concentrations in cirrhotic patients with hepatic encephalopathy: relationship to severity of encephalopathy and to pharmaceutical benzodiazepine intake.
abstract: Increased plasma and CSF concentrations of substances which bind to brain benzodiazepine receptors have previously been reported in cirrhotic patients with hepatic encephalopathy (HE). However, their relationship to previous intake of pharmaceutical benzodiazepines has not been clearly established. In the present study, plasma levels of benzodiazepine receptor ligands (BZRLs) were measured using a sensitive radioreceptor assay in 12 control subjects with no evidence of hepatic, neurological or psychiatric illness, 11 cirrhotic patients without HE, 24 cirrhotic patients with moderate (grade I-II) HE and in 45 cirrhotic patients with severe (grade II-IV) HE. In addition, CSF concentrations of BZRLs were measured in 8 cirrhotic patients with HE and an equal number of age-matched controls. Recent intake (within 10 days) of pharmaceutical 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 BZRLs 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 accounted for by prior exposure to benzodiazepine medication in all cases. CSF concentrations of BZRLs in cirrhotic patients were not significantly different from control values. These findings do not support a role for "endogenous" benzodiazepines in the pathogenesis of HE in chronic liver disease but suggest that pharmaceutic benzodiazepines administered to cirrhotic patients as sedatives or as part of endoscopic work-up could have contributed to the neurological impairment in some patients.
authors.affiliation: Centre Hospitalier Universitaire, Hôpital Saint-Eloi, Montpellier, France.
authors.forename: P
authors.initials: P
authors.lastname: Perney
authors.forename: R F
authors.initials: RF
authors.lastname: Butterworth
authors.forename: D D
authors.initials: DD
authors.lastname: Mousseau
authors.forename: J
authors.initials: J
authors.lastname: Lavoie
authors.forename: P
authors.initials: P
authors.lastname: Fabbro-Peray
authors.forename: F
authors.initials: F
authors.lastname: Blanc
authors.forename: G P
authors.initials: GP
authors.lastname: Layrargues
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002458:Cell Fractionation; D002531:Cerebellum; D002908:Chronic Disease; D002998:Clonazepam / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D006501:Hepatic Encephalopathy / Q000097:blood* / Q000134:cerebrospinal fluid*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008103:Liver Cirrhosis / Q000097:blood / Q000134:cerebrospinal fluid; D010076:Oxazepam / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D014316:Tritium
chemical_list: D018757:GABA Modulators; D007546:Isoquinolines; D011963:Receptors, GABA-A; D014316:Tritium; D001569:Benzodiazepines; D005442:Flumazenil; D002998:Clonazepam; D010076:Oxazepam; D003975:Diazepam; C037850:PK 11195