Biliary bile acids in primary biliary cirrhosis: effect of ursodeoxycholic acid.
Bile acid composition in fasting duodenal bile was assessed at entry and at 2 years in patients with primary biliary cirrhosis (PBC) enrolled in a randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) (10-12 mg/kg/d) taken as a single bedtime dose. Specimens were analyzed by a high-pressure liquid chromatography method that had been validated against gas chromatography. Percent composition in bile (mean +/- SD) for 98 patients at entry for cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA), lithocholic (LCA), and ursodeoxycholic (UDCA) acids, respectively, were 57.4 +/- 18.6, 31.5 +/- 15.5, 8.0 +/- 9.3, 0.3 +/- 1.0, and 0.6 +/- 0.9. Values for CA were increased, whereas those for CDCA, DCA, LCA, and UDCA were decreased when compared with values in normal persons. Bile acid composition of the major bile acids did not change after 2 years on placebo medication. By contrast, in patients receiving UDCA for 2 years, bile became enriched with UDCA on average to 40.1%, and significant decreases were noted for CA (to 32.2%) and CDCA (to 19.5%). No change in percent composition was observed for DCA and LCA. Percent composition at entry and changes in composition after 2 years on UDCA were similar in patients with varying severity of PBC. In patients whose bile was not enriched in UDCA (entry and placebo-treated specimens), CA, CDCA, DCA, and the small amount of UDCA found in some of these specimens were conjugated to a greater extent with glycine (52%-64%) than with taurine (36%-48%). Treatment with UDCA caused the proportion of all endogenous bile acids conjugated with glycine to increase to 69% to 78%, while the proportion conjugated with taurine (22%-31%) fell (P <.05). Administered UDCA was also conjugated predominantly with glycine (87%).
Combes
B
B
University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
Carithers
R L
RL
Maddrey
W C
WC
Munoz
S
S
Garcia-Tsao
G
G
Bonner
G F
GF
Boyer
J L
JL
Luketic
V A
VA
Shiffman
M L
ML
Peters
M G
MG
White
H
H
Zetterman
R K
RK
Risser
R
R
Rossi
S S
SS
Hofmann
A F
AF
D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000032:analysis*; D002635:Chenodeoxycholic Acid / Q000032:analysis; D019826:Cholic Acid / Q000032:analysis; D002849:Chromatography, Gas / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003840:Deoxycholic Acid / Q000032:analysis; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008095:Lithocholic Acid / Q000032:analysis; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012044:Regression Analysis; D015203:Reproducibility of Results; D013997:Time Factors; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000627:therapeutic use*
D001647:Bile Acids and Salts; D010919:Placebos; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D008095:Lithocholic Acid; D014580:Ursodeoxycholic Acid; D019826:Cholic Acid