[Drug clearance as a decision aid for further invasive liver diagnosis--studies with hexobarbital as a model substrate].
The clearance of a drug predominantly metabolized in the liver may serve as an estimate of quantitative liver function. In 260 consecutive patients presenting with a history of liver disease and abnormal laboratory findings but without a current definite diagnosis we have measured the clearance of hexobarbital and investigated if low values in patients are able to support the decision for an invasive diagnostic procedure such as needle biopsy or laparoscopy. 250 mg of hexobarbital was given orally to the patients between 8 and 10 hrs p.m. 12 hrs later blood samples were taken. Hexobarbital was determined by gas chromatography with N-selective detection, and a single point clearance was calculated. We recommended liver biopsy or laparoscopy to all patients with a hexobarbital clearance below 2.7 ml/min/kg body weight (normal 2.66-5.34 ml/min/kg). 73 out of 260 patients showed a reduced hexobarbital clearance. In 44 patients blind liver biopsy (n = 14) or laparoscopy (n = 30) was performed, 29 patients refused an invasive diagnostic procedure. 17 out of 26 patients with the tentative diagnosis chronic hepatitis had already an incomplete or complete liver cirrhosis. In 11 out of 18 patients with the tentative diagnosis alcohol toxic liver injury we found a progressive portal fibrosis or complete liver cirrhosis. Reduced drug clearance reflecting quantitative liver function can be an indicator of advanced liver disease, thus adding substantially to the decision for further invasive diagnostic procedures.
Zilly
W
W
Hartwald-Klinik der BfA Bad Brückenau.
Richter
E
E
D019405:Cytochrome P-450 CYP11B2; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D003937:Diagnosis, Differential; D006521:Hepatitis, Chronic / Q000097:blood / Q000175:diagnosis; D006591:Hexobarbital / Q000493:pharmacokinetics; D006801:Humans; D010535:Laparoscopy; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis; D008107:Liver Diseases / Q000097:blood / Q000175:diagnosis*; D008111:Liver Function Tests / Q000379:methods*; D008657:Metabolic Clearance Rate / Q000502:physiology; D008862:Microsomes, Liver / Q000201:enzymology; D012016:Reference Values; D013250:Steroid Hydroxylases / Q000502:physiology
D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; D013250:Steroid Hydroxylases; D019405:Cytochrome P-450 CYP11B2