OBJECTIVE: Hepatic encephalopathy (HE) is a complex neuropsychiatric disorder secondary to acute or chronic liver failure. Although the exact causes of HE have not been clarified, enhanced central nervous system inhibition at the gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex, mediated by increased levels of endogenous benzodiazepine-receptor ligands (BZRL), has been proposed. Research exploring this hypothesis has yielded contradictory findings. This study evaluated the presence and levels of BZRL in plasma from patients with HE and 3 comparison groups. DESIGN: Cross-sectional study. PATIENTS: Twenty-four patients with HE, 10 patients with liver cirrhosis without encephalopathy (LC), 4 patients with uremic encephalopathy (UE), and 9 healthy subjects. INTERVENTIONS: Radio-receptor assay of plasma samples from patients and controls. MAIN OUTCOME MEASURES: Plasma levels of BZRL. RESULTS: The patients in the HE group had significantly higher plasma BZRL levels than the patients with UE and the healthy subjects, but not than those with LC, in whom these compounds were also detected in significant concentrations. When patients were classified according to the severity of HE, plasma of BZRL showed a modest correlation with stage of severity (r = 0.37). Interestingly, approximately one-third of the patients with HE did not have detectable levels of BZRL. CONCLUSION: Endogenous BZRL may play a role in the pathogenesis of HE, although neuropsychiatric symptoms in HE are difficult to explain in terms of these compounds alone.
OBJECTIVE:Hepatic encephalopathy (HE) is a complex neuropsychiatric disorder secondary to acute or chronic liver failure. Although the exact causes of HE have not been clarified, enhanced central nervous system inhibition at the gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex, mediated by increased levels of endogenous benzodiazepine-receptor ligands (BZRL), has been proposed. Research exploring this hypothesis has yielded contradictory findings. This study evaluated the presence and levels of BZRL in plasma from patients with HE and 3 comparison groups. DESIGN: Cross-sectional study. PATIENTS: Twenty-four patients with HE, 10 patients with liver cirrhosis without encephalopathy (LC), 4 patients with uremic encephalopathy (UE), and 9 healthy subjects. INTERVENTIONS: Radio-receptor assay of plasma samples from patients and controls. MAIN OUTCOME MEASURES: Plasma levels of BZRL. RESULTS: The patients in the HE group had significantly higher plasma BZRL levels than the patients with UE and the healthy subjects, but not than those with LC, in whom these compounds were also detected in significant concentrations. When patients were classified according to the severity of HE, plasma of BZRL showed a modest correlation with stage of severity (r = 0.37). Interestingly, approximately one-third of the patients with HE did not have detectable levels of BZRL. CONCLUSION: Endogenous BZRL may play a role in the pathogenesis of HE, although neuropsychiatric symptoms in HE are difficult to explain in terms of these compounds alone.
Authors: A S Basile; R D Hughes; P M Harrison; Y Murata; L Pannell; E A Jones; R Williams; P Skolnick Journal: N Engl J Med Date: 1991-08-15 Impact factor: 91.245
Authors: A S Basile; P M Harrison; R D Hughes; Z Q Gu; L Pannell; A McKinney; E A Jones; R Williams Journal: Hepatology Date: 1994-01 Impact factor: 17.425
Authors: M Olasmaa; J D Rothstein; A Guidotti; R J Weber; S M Paul; S Spector; M L Zeneroli; M Baraldi; E Costa Journal: J Neurochem Date: 1990-12 Impact factor: 5.372
Authors: G Pomier-Layrargues; J F Giguère; J Lavoie; P Perney; S Gagnon; M D'Amour; J Wells; R F Butterworth Journal: Hepatology Date: 1994-01 Impact factor: 17.425
Authors: A S Basile; L Pannell; T Jaouni; S H Gammal; H M Fales; E A Jones; P Skolnick Journal: Proc Natl Acad Sci U S A Date: 1990-07 Impact factor: 11.205