Endogenous benzodiazepine-like compounds and diazepam binding inhibitor in serum of patients with liver cirrhosis with and without overt encephalopathy.
OBJECTIVE
Despite some controversy, it has been suggested that endogenous benzodiazepine plays a role in the pathogenesis of hepatic encephalopathy. The aim of the present study was to evaluate the concentrations of endogenous benzodiazepines and the peptide, diazepam binding inhibitor, in the blood of patients with liver cirrhosis with and without overt encephalopathy, and to compare these levels with those of consumers of commercial benzodiazepines.


METHODS
Normal subjects (90), benzodiazepine consumers (14), and cirrhotic patients (113) were studied.


METHODS
Endogenous benzodiazepines were measured by the radioligand binding technique after high performance liquid chromatography (HPLC) purification. The presence of diazepam and N-desmethyldiazepam was assayed by HPLC-electrospray tandem mass spectrometry. Diazepam binding inhibitor was studied in serum by radioimmunoassay.


RESULTS
Endogenous benzodiazepines were below the limit of detection in 7% of patients with encephalopathy. When detectable, their levels were at least comparable with those of benzodiazepine consumers and correlated with the liver dysfunction but not the stage of encephalopathy. Serum levels of diazepam binding inhibitor tended to decrease when endogenous benzodiazepines levels increased.


CONCLUSIONS
Endogenous benzodiazepines may accumulate in patients with liver cirrhosis during the course of the disease, and the phenomenon appears to be independent of the presence or absence of encephalopathy.
Cattedra di Semeiotica e Metodologia Medica, Università di Modena, Italy.
R
R
Avallone
M L
ML
Zeneroli
I
I
Venturini
L
L
Corsi
P
P
Schreier
M
M
Kleinschnitz
C
C
Ferrarese
F
F
Farina
C
C
Baraldi
N
N
Pecora
M
M
Frigo
M
M
Baraldi
D000368:Aged; D001569:Benzodiazepines / Q000008:administration & dosage / Q000097:blood*; D002352:Carrier Proteins / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D026261:Diazepam Binding Inhibitor; D005260:Female; D006501:Hepatic Encephalopathy / Q000097:blood* / Q000209:etiology; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged
D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; D001569:Benzodiazepines