Biliary secretion of bile acids and lipids in primary sclerosing cholangitis. Influence of cholestasis and effect of ursodeoxycholic acid treatment.
In patients with primary sclerosing cholangitis cholestasis is a prominent feature of the disease. We studied the effect of cholestasis and of ursodeoxycholic acid treatment on the biliary secretion of bile acids and lipids in ten patients with primary sclerosing cholangitis. Ursodeoxycholic acid treatment for 3 months led to an increase in the biliary secretion rates of total bile acids from 0.91 mmol/h to 1.47 mmol/h, mainly due to an increase in urosodeoxycholic acid, which represented 31% of biliary bile acids. With increasing cholestasis, the biliary enrichment of the bile acid pool with urosodeoxycholic acid decreased. Biliary output of endogenous bile acids on average was unchanged, but in patients with cholestasis and diminished output before treatment, it increased after ursodeoxycholic acid. Phospholipid secretion increased from 0.26 mmol/h to 0.43 mmol/h without correlation to the degree of cholestasis. Biliary cholesterol secretion on average was unchanged after ursodeoxycholic acid (0.1 versus 0.09 mmol/h) but, in patients with cholestasis and diminished output before treatment, it increased after ursodeoxycholic acid. The decreasing enrichment of the bile acid pool with ursodeoxycholic acid with increasing cholestasis may be related to its slight effect in advanced disease. The increase in biliary phospholipid secretion may represent another mechanism of action of urosodeoxycholic acid responsible for its beneficial effect in cholestatic liver disease.
Stiehl
A
A
Department of Medicine, University of Heidelberg, Germany.
Rudolph
G
G
Sauer
P
P
Theilmann
L
L
D000293:Adolescent; D000328:Adult; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D015209:Cholangitis, Sclerosing / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D002779:Cholestasis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid