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norUrsodeoxycholic acid improves cholestasis in primary sclerosing cholangitis
- Source :
- Journal of Hepatology. 67(3):549-558
-
Abstract
- Background & Aim: Primary sclerosing cholangitis (PSC) represents a devastating bile duct disease, currently lacking effective medical therapy. 24-norursodeoxycholic acid (norUDCA) is a side chain-shortened C-23 homologue of UDCA and has shown potent anti-cholestatic, anti-inflammatory and anti-fibrotic properties in a preclinical PSC mouse model. A randomized controlled trial, including 38 centers from 12 European countries, evaluated the safety and efficacy of three doses of oral norUDCA (500 mg/d, 1,000 mg/d or 1,500 mg/d) compared with placebo in patients with PSC. Methods: One hundred sixty-one PSC patients without concomitant UDCA therapy and with elevated serum alkaline phosphatase (ALP) levels were randomized for a 12-week treatment followed by a 4-week follow-up. The primary efficacy endpoint was the mean relative change in ALP levels between baseline and end of treatment visit. Results: norUDCA reduced ALP levels by -12.3%, -17.3%, and -26.0% in the 500, 1,000, and 1,500 mg/d groups (p = 0.029, tively, while a +1.2% increase was observed in the placebo group. Similar dose-dependent results were found for secondary end-points, such as ALT, AST, gamma-GT, or the rate of patients achieving ALP levels
- Subjects :
- Male
0301 basic medicine
LIVER FIBROSIS
Gastroenterology
law.invention
0302 clinical medicine
Primary biliary cirrhosis
Randomized controlled trial
law
QUALITY-OF-LIFE
Medicine
BILE-ACIDS
Cholestasis
Orvostudományok
Middle Aged
Side chain-shortened bile acids
Ursodeoxycholic acid
3. Good health
SURVIVAL
Alkaline phosphatase
Female
030211 gastroenterology & hepatology
medicine.drug
Adult
medicine.medical_specialty
Cholangitis, Sclerosing
Placebo
Klinikai orvostudományok
CONTROLLED-TRIAL
Primary sclerosing cholangitis
Cholehepatic shunting
03 medical and health sciences
Double-Blind Method
INFLAMMATION
Internal medicine
Humans
PRIMARY BILIARY-CIRRHOSIS
Dose-Response Relationship, Drug
Hepatology
business.industry
DOSE URSODEOXYCHOLIC ACID
medicine.disease
030104 developmental biology
ALKALINE-PHOSPHATASE
Concomitant
3121 General medicine, internal medicine and other clinical medicine
Bile acid treatment
business
KNOCKOUT MICE
Sclerosing cholangitis
Subjects
Details
- Language :
- English
- ISSN :
- 01688278
- Volume :
- 67
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of Hepatology
- Accession number :
- edsair.doi.dedup.....21b411b8bf897c7e4babee6aa92ebaca
- Full Text :
- https://doi.org/10.1016/j.jhep.2017.05.009