Abstract
The efficiency of bile acid conjugation before and during therapy with 600 mg/day of ursodeoxycholic acid was measured in seven adult patients with early chronic cholestatic liver disease (6 with primary biliary cirrhosis; 1 with primary sclerosing cholangitis). Duodenal bile samples were obtained by aspiration and the proportion of unconjugated bile acids was determined using lipophilic anion exchange chromatography to separate bile acid classes, followed by analysis of individual bile acids by gas chromatography-mass spectrometry. The proportion of conjugated bile acids was determined by high-performance liquid chromatography. Use of a 99mTc-HIDA recovery marker permitted the absolute mass of unconjugated bile acids in the gallbladder to be calculated. Unconjugated bile acids comprised 0.4% of total biliary bile acids before and 0.2% during ursodeoxycholic acid therapy, indicating highly efficient conjugation of bile acids. During therapy, percentage unconjugated ursodeoxycholic acid significantly increased from (mean ± S.D.) 13 ± 13% to 54 ± 12%; P <0.002. When the unconjugated and conjugated fractions of bile acids were compared, there was an enrichment in unconjugated fraction for cholic acid and ursodeoxycholic acid and a depletion for chenodeoxycholic acid both in basal condition and during ursodeoxycholic acid therapy, suggesting that hydrophilic bile acids were conjugated less efficiently. During therapy, the conjugation efficiency significantly increased for cholic acid and ursodeoxycholic acid. The pretreatment mass of total unconjugated bile acids in the gallbladder was (mean ± S.D.) 4.4 ± 3.2 μmol, and was not significantly changed by ursodeoxycholic acid therapy (6.2 ± 3.5 μmol). However, ursodeoxycholic acid therapy caused a significant increase in the mass of unconjugated ursodeoxycholic acid. It is concluded that endogenous bile acids and exogenous ursodeoxycholic acid when given at the usual dose are efficiently conjugated in patients with early cholestatic liver disease. Despite showing increased biliary unconjugated ursodeoxcholic acid during its oral administration, our data do not lend support to the occurrence of hypercholeresis due to cholehepatic shunting of bile acids.
| Original language | English |
|---|---|
| Pages (from-to) | 175-185 |
| Number of pages | 11 |
| Journal | Clinica Chimica Acta |
| Volume | 248 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Apr 30 1996 |
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Keywords
- bile acid conjugation efficiency
- cholehepatic shunting
- cholestasis
- primary biliary cirrhosis
- primary sclerosing cholangitis
- unconjugated bile acids
- ursodeoxycholic acid
ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry
Cite this
Bile acid conjugation in early stage cholestatic liver disease before and during treatment with ursodeoxycholic acid. / Fracchia, Mario; Setchell, Kenneth D R; Crosignani, Andrea; Podda, Mauro; O'Connell, Nancy; Ferraris, Roberto; Hofmann, Alan F.; Galatola, Giovanni.
In: Clinica Chimica Acta, Vol. 248, No. 2, 30.04.1996, p. 175-185.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Bile acid conjugation in early stage cholestatic liver disease before and during treatment with ursodeoxycholic acid
AU - Fracchia, Mario
AU - Setchell, Kenneth D R
AU - Crosignani, Andrea
AU - Podda, Mauro
AU - O'Connell, Nancy
AU - Ferraris, Roberto
AU - Hofmann, Alan F.
AU - Galatola, Giovanni
PY - 1996/4/30
Y1 - 1996/4/30
N2 - The efficiency of bile acid conjugation before and during therapy with 600 mg/day of ursodeoxycholic acid was measured in seven adult patients with early chronic cholestatic liver disease (6 with primary biliary cirrhosis; 1 with primary sclerosing cholangitis). Duodenal bile samples were obtained by aspiration and the proportion of unconjugated bile acids was determined using lipophilic anion exchange chromatography to separate bile acid classes, followed by analysis of individual bile acids by gas chromatography-mass spectrometry. The proportion of conjugated bile acids was determined by high-performance liquid chromatography. Use of a 99mTc-HIDA recovery marker permitted the absolute mass of unconjugated bile acids in the gallbladder to be calculated. Unconjugated bile acids comprised 0.4% of total biliary bile acids before and 0.2% during ursodeoxycholic acid therapy, indicating highly efficient conjugation of bile acids. During therapy, percentage unconjugated ursodeoxycholic acid significantly increased from (mean ± S.D.) 13 ± 13% to 54 ± 12%; P <0.002. When the unconjugated and conjugated fractions of bile acids were compared, there was an enrichment in unconjugated fraction for cholic acid and ursodeoxycholic acid and a depletion for chenodeoxycholic acid both in basal condition and during ursodeoxycholic acid therapy, suggesting that hydrophilic bile acids were conjugated less efficiently. During therapy, the conjugation efficiency significantly increased for cholic acid and ursodeoxycholic acid. The pretreatment mass of total unconjugated bile acids in the gallbladder was (mean ± S.D.) 4.4 ± 3.2 μmol, and was not significantly changed by ursodeoxycholic acid therapy (6.2 ± 3.5 μmol). However, ursodeoxycholic acid therapy caused a significant increase in the mass of unconjugated ursodeoxycholic acid. It is concluded that endogenous bile acids and exogenous ursodeoxycholic acid when given at the usual dose are efficiently conjugated in patients with early cholestatic liver disease. Despite showing increased biliary unconjugated ursodeoxcholic acid during its oral administration, our data do not lend support to the occurrence of hypercholeresis due to cholehepatic shunting of bile acids.
AB - The efficiency of bile acid conjugation before and during therapy with 600 mg/day of ursodeoxycholic acid was measured in seven adult patients with early chronic cholestatic liver disease (6 with primary biliary cirrhosis; 1 with primary sclerosing cholangitis). Duodenal bile samples were obtained by aspiration and the proportion of unconjugated bile acids was determined using lipophilic anion exchange chromatography to separate bile acid classes, followed by analysis of individual bile acids by gas chromatography-mass spectrometry. The proportion of conjugated bile acids was determined by high-performance liquid chromatography. Use of a 99mTc-HIDA recovery marker permitted the absolute mass of unconjugated bile acids in the gallbladder to be calculated. Unconjugated bile acids comprised 0.4% of total biliary bile acids before and 0.2% during ursodeoxycholic acid therapy, indicating highly efficient conjugation of bile acids. During therapy, percentage unconjugated ursodeoxycholic acid significantly increased from (mean ± S.D.) 13 ± 13% to 54 ± 12%; P <0.002. When the unconjugated and conjugated fractions of bile acids were compared, there was an enrichment in unconjugated fraction for cholic acid and ursodeoxycholic acid and a depletion for chenodeoxycholic acid both in basal condition and during ursodeoxycholic acid therapy, suggesting that hydrophilic bile acids were conjugated less efficiently. During therapy, the conjugation efficiency significantly increased for cholic acid and ursodeoxycholic acid. The pretreatment mass of total unconjugated bile acids in the gallbladder was (mean ± S.D.) 4.4 ± 3.2 μmol, and was not significantly changed by ursodeoxycholic acid therapy (6.2 ± 3.5 μmol). However, ursodeoxycholic acid therapy caused a significant increase in the mass of unconjugated ursodeoxycholic acid. It is concluded that endogenous bile acids and exogenous ursodeoxycholic acid when given at the usual dose are efficiently conjugated in patients with early cholestatic liver disease. Despite showing increased biliary unconjugated ursodeoxcholic acid during its oral administration, our data do not lend support to the occurrence of hypercholeresis due to cholehepatic shunting of bile acids.
KW - bile acid conjugation efficiency
KW - cholehepatic shunting
KW - cholestasis
KW - primary biliary cirrhosis
KW - primary sclerosing cholangitis
KW - unconjugated bile acids
KW - ursodeoxycholic acid
UR - http://www.scopus.com/inward/record.url?scp=0030003493&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030003493&partnerID=8YFLogxK
U2 - 10.1016/0009-8981(95)06252-1
DO - 10.1016/0009-8981(95)06252-1
M3 - Article
C2 - 8740581
AN - SCOPUS:0030003493
VL - 248
SP - 175
EP - 185
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
SN - 0009-8981
IS - 2
ER -