title: Kinetics of hepatic bile acid handling in cholestatic liver disease: effect of ursodeoxycholic acid.
abstract: OBJECTIVE
  Ursodeoxycholic acid (UDCA) is clinically beneficial in chronic cholestatic liver disease, but the underlying mechanisms are unclear. It has been suggested that intrahepatic retention of endogenous hydrophobic bile acids contributes to cholestasis and that the hydrophilic bile acid UDCA reduces this retention; the aim of our study was to test these hypotheses.
  
  
  METHODS
  Twelve patients with primary biliary cirrhosis (PBC) and 5 with primary sclerosing cholangitis (PSC) were studied before and during UDCA (10 mg.kg-1.day-1) and compared with 11 healthy controls. Following intravenous 75Se labeled homocholic acid taurine (75SeHCAT) in the fasting state, abdominal gamma camera imaging was performed for 90 minutes. Initial hepatic uptake, transit time, net, and absolute excretory rates for 75SeHCAT were measured.
  
  
  RESULTS
  Mean initial hepatic uptake was not different between patients and controls (17.2% and 19.9% dose/minute, not significant). However, net and absolute excretory rates were significantly reduced in patients (1.4% vs. 3.7% dose/minute, P < 0.0001; and 2.35% vs. 3.96% dose/minute, P < 0.02, respectively), and hepatic transit time was prolonged (18.7 minutes vs. 11.6 minutes, P < 0.002). UDCA improved net and absolute hepatic excretory rates and transit time (1.43% to 1.96% dose/minute, P < 0.001; 2.35% to 3.15% dose/minute, P < 0.005 and 18.7 to 14.7 minutes, P < 0.001, respectively). However, UDCA did not alter initial hepatic uptake.
  
  
  CONCLUSIONS
  In PBC and PSC, there is a defect in hepatic bile acid excretion but not in uptake, implying bile acid retention. This retention is reduced by UDCA.
authors.affiliation: Department of Biochemical Medicine, St. George's Hospital Medical School, London, England.
authors.forename: R P
authors.initials: RP
authors.lastname: Jazrawi
authors.forename: J S
authors.initials: JS
authors.lastname: de Caestecker
authors.forename: P M
authors.initials: PM
authors.lastname: Goggin
authors.forename: A J
authors.initials: AJ
authors.lastname: Britten
authors.forename: A E
authors.initials: AE
authors.lastname: Joseph
authors.forename: J D
authors.initials: JD
authors.lastname: Maxwell
authors.forename: T C
authors.initials: TC
authors.lastname: Northfield
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001647:Bile Acids and Salts / Q000378:metabolism*; D015209:Cholangitis, Sclerosing / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D001647:Bile Acids and Salts; D014580:Ursodeoxycholic Acid