| Bile acid changes after high-dose ursodeoxycholic acid treatment in primary sclerosing cholangitis: Relation to disease progression. | |
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MedLine Citation:
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PMID: 20564380 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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High-dose (28-30 mg/kg/day) ursodeoxycholic acid (UDCA) treatment improves serum liver tests in patients with primary sclerosing cholangitis (PSC) but does not improve survival and is associated with increased rates of serious adverse events. The mechanism for the latter undesired effect remains unclear. High-dose UDCA could result in the production of hepatotoxic bile acids, such as lithocholic acid (LCA), because of limited small bowel absorption of UDCA and conversion of UDCA by bacteria in the colon. We determined the serum bile acid composition in 56 patients with PSC previously enrolled in a randomized, double-blind controlled trial of high-dose UDCA versus placebo. Samples for analysis were obtained at the baseline and at the end of treatment. The mean changes in the UDCA level (16.86 versus 0.05 micromol/L) and total bile acid level (17.21 versus -0.55 micromol/L) were significantly higher in the UDCA group (n = 29) versus the placebo group (n = 27) when pretreatment levels were compared (P < 0.0001). LCA was also markedly increased (0.22 versus 0.01 micromol/L) in the UDCA group compared to the placebo group (P = 0.001). No significant changes were detected for cholic acid, deoxycholic acid, or chenodeoxycholic acid. Patients (n = 9) in the UDCA group who reached clinical endpoints of disease progression (the development of cirrhosis, varices, liver transplantation, or death) tended to have greater increases in their posttreatment total bile acid levels (34.99 versus 9.21 micromol/L, P < 0.08) in comparison with those who did not. CONCLUSION: High-dose UDCA treatment in PSC patients results in marked UDCA enrichment and significant expansion of the total serum bile acid pool, including LCA. |
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Authors:
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Emmanouil Sinakos; Hanns-Ulrich Marschall; Kris V Kowdley; Alex Befeler; Jill Keach; Keith Lindor |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: 52 ISSN: 1527-3350 ISO Abbreviation: Hepatology Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-01 Completed Date: 2010-07-19 Revised Date: 2011-08-10 |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: United States |
Other Details:
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Languages: eng Pagination: 197-203 Citation Subset: IM |
Affiliation:
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Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Bile Acids and Salts / blood* Cholagogues and Choleretics / administration & dosage*, blood Cholangitis, Sclerosing / blood, drug therapy* Disease Progression Dose-Response Relationship, Drug Double-Blind Method Female Humans Lithocholic Acid / blood Male Middle Aged Randomized Controlled Trials as Topic Treatment Outcome Ursodeoxycholic Acid / administration & dosage*, blood Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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DK56924/DK/NIDDK NIH HHS; R01 DK056924-05/DK/NIDDK NIH HHS; R01 DK056924-10/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bile Acids and Salts; 0/Cholagogues and Choleretics; 128-13-2/Ursodeoxycholic Acid; 434-13-9/Lithocholic Acid |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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