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norUrsodeoxycholic ...
norUrsodeoxycholic acid improves cholestasis in primary sclerosing cholangitis
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Fickert, P. (author)
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Hirschfield, G. M. (author)
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Denk, G. (author)
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- Marschall, Hanns-Ulrich, 1954 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine
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Altorjay, I. (author)
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Farkkila, M. (author)
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Schramm, C. (author)
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Spengler, U. (author)
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Chapman, R. (author)
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Bergquist, A. (author)
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Schrumpf, E. (author)
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Nevens, F. (author)
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Trivedi, P. (author)
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Reiter, F. P. (author)
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Tornai, I. (author)
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Halilbasic, E. (author)
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Greinwald, R. (author)
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Prols, M. (author)
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Manns, M. P. (author)
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Trauner, M. (author)
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European, P. S. C. norUDCA Study Grp (author)
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(creator_code:org_t)
- 2017
- 2017
- English.
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In: J Hepatol. - 0168-8278. ; 67:3, s. 549-558
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https://gup.ub.gu.se...
Abstract
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- 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 < 1.5 x ULN. Serious adverse events occurred in seven patients in the 500 mg/d, five patients in the 1,000 mg/d, two patients in the 1500 mg/d group, and three in the placebo group. There was no difference in reported pruritus between treatment and placebo groups. Conclusions: norUDCA significantly reduced ALP values dose-dependently in all treatment arms. The safety profile of norUDCA was excellent and comparable to placebo. Consequently, these results justify a phase III trial of norUDCA in PSC patients. Lay summary: Effective medical therapy for primary sclerosing cholangitis (PSC) is urgently needed. In this phase II clinical study in PSC patients, a side chain-shortened derivative of ursodeoxycholic acid, norursodeoxycholic acid (norUDCA), significantly reduced serum alkaline phosphatase levels in a dose-dependent manner during a 12-week treatment. Importantly, norUDCA showed a favorable safety profile, which was similar to placebo. The use of norUDCA in PSC patients is promising and will be further evaluated in a phase III clinical study. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- Alkaline phosphatase
- Bile acid treatment
- Cholestasis
- Sclerosing cholangitis
- Side chain-shortened bile acids
- Cholehepatic shunting
- Ursodeoxycholic acid
- primary biliary-cirrhosis
- dose ursodeoxycholic acid
- quality-of-life
- alkaline-phosphatase
- bile-acids
- controlled-trial
- liver fibrosis
- knockout mice
- survival
- inflammation
- Gastroenterology & Hepatology
- azouilleres o
- 1990
- journal of hepatology
- v11
- p120
Publication and Content Type
- ref (subject category)
- art (subject category)
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J Hepatol
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- By the author/editor
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Fickert, P.
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Hirschfield, G. ...
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Denk, G.
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Marschall, Hanns ...
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Altorjay, I.
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Farkkila, M.
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show more...
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Schramm, C.
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Spengler, U.
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Chapman, R.
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Bergquist, A.
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Schrumpf, E.
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Nevens, F.
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Trivedi, P.
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Reiter, F. P.
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Tornai, I.
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Halilbasic, E.
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Greinwald, R.
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Prols, M.
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Manns, M. P.
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Trauner, M.
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European, P. S. ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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J Hepatol
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University of Gothenburg