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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-5484

Beuers, U; Kullak-Ublick, G A; Pusl, T; Rauws, E R; Rust, C (2009). Medical treatment of primary sclerosing cholangitis: A role for novel bile acids and other (post-)transcriptional modulators? Clinical Reviews in Allergy and Immunology, 36(1):52-61.

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Abstract

Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic disease of the liver and bile ducts that is associated with inflammatory bowel disease, generally leads to end-stage liver disease, and is complicated by malignancies of the biliary tree and the large intestine. The pathogenesis of PSC remains enigmatic, making the development of targeted therapeutic strategies difficult. Immunosuppressive and antifibrotic therapeutic agents were ineffective or accompanied by major side effects. Ursodeoxycholic acid (UDCA) has consistently been shown to improve serum liver tests and might lower the risk of colon carcinoma and cholangiocarcinoma by yet unknown mechanisms. Whether "high dose" UDCA improves the long-term prognosis in PSC as suggested by small pilot trials remains to be demonstrated. The present overview discusses potential therapeutic options aside of targeted immunological therapies and UDCA. The C23 bile acid norUDCA has been shown to markedly improve biochemical and histological features in a mouse model of sclerosing cholangitis without any toxic effects. Studies in humans are eagerly being awaited. Nuclear receptors like the farnesoid-X receptor (FXR), pregnane-X receptor (PXR), vitamin D receptor (VDR), and peroxisome-proliferator-activator receptors (PPARs) have been shown to induce expression of diverse carriers and biotransformation enzymes of the intestinal and hepatic detoxification machinery and/or to modulate fibrogenesis. Pros and cons of respective receptor agonists for the future treatment of PSC are discussed in detail. In our view, the novel bile acid norUDCA and agonists of PPARs, VDR, and PXR appear particularly attractive for further studies in PSC.

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology
DDC:610 Medicine & health
Language:English
Date:February 2009
Deposited On:17 Nov 2008 08:49
Last Modified:27 Nov 2013 23:33
Publisher:Springer
ISSN:1080-0549
Publisher DOI:10.1007/s12016-008-8085-y
PubMed ID:18751930
Citations:Web of Science®. Times Cited: 12
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Scopus®. Citation Count: 12

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