Universität zu Köln

Kremer, Andreas E., van Dijk, Remco, Leckie, Pamela, Schaap, Frank G., Kuiper, Edith M. M., Mettang, Thomas, Reiners, Katrin S., Raap, Ulrike, van Buuren, Henk R., van Erpecum, Karel J., Davies, Nathan A., Rust, Christian, Engert, Andreas, Jalan, Rajiv, Elferink, Ronald P. J. Oude and Beuers, Ulrich (2012). Serum autotaxin is increased in pruritus of cholestasis, but not of other origin, and responds to therapeutic interventions. Hepatology, 56 (4). S. 1391 - 1401. HOBOKEN: WILEY. ISSN 1527-3350

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Abstract

Pruritus is a seriously disabling symptom accompanying many cholestatic liver disorders. Recent experimental evidence implicated the lysophospholipase, autotaxin (ATX), and its product, lysophosphatidic acid (LPA), as potential mediators of cholestatic pruritus. In this study, we highlight that increased serum ATX levels are specific for pruritus of cholestasis, but not pruritus of uremia, Hodgkin's disease, or atopic dermatitis. Treatment of patients with cholestasis with the bile salt sequestrant, colesevelam, but not placebo, effectively reduced total serum bile salts and fibroblast growth factor 19 levels, but only marginally altered pruritus intensity and ATX activity. Rifampicin (RMP) significantly reduced itch intensity and ATX activity in patients with pruritus not responding to bile salt sequestrants. In vitro, RMP inhibited ATX expression in human HepG2 hepatoma cells and hepatoma cells overexpressing the pregnane X receptor (PXR), but not in hepatoma cells in which PXR was knocked down. Treatment of severe, refractory pruritus by the molecular adsorbents recirculation system or nasobiliary drainage improved itch intensity, which, again, correlated with the reduction of ATX levels. Upon reoccurrence of pruritus, ATX activity returned to pretreatment values. Conclusion: Serum ATX activity is specifically increased in patients with cholestatic, but not other forms of, systemic pruritus and closely correlates with the effectiveness of therapeutic interventions. The beneficial antipruritic action of RMP may be explained, at least partly, by the PXR-dependent transcriptional inhibition of ATX expression. Thus, ATX likely represents a novel therapeutic target for pruritus of cholestasis. (HEPATOLOGY 2012)

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kremer, Andreas E. UNSPECIFIED UNSPECIFIED UNSPECIFIED van Dijk, Remco UNSPECIFIED UNSPECIFIED UNSPECIFIED Leckie, Pamela UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaap, Frank G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuiper, Edith M. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mettang, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Reiners, Katrin S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Raap, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED van Buuren, Henk R. UNSPECIFIED UNSPECIFIED UNSPECIFIED van Erpecum, Karel J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Davies, Nathan A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rust, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Engert, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Jalan, Rajiv UNSPECIFIED UNSPECIFIED UNSPECIFIED Elferink, Ronald P. J. Oude UNSPECIFIED UNSPECIFIED UNSPECIFIED Beuers, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-482428
DOI:	10.1002/hep.25748
Journal or Publication Title:	Hepatology
Volume:	56
Number:	4
Page Range:	S. 1391 - 1401
Date:	2012
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1527-3350
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LYSOPHOSPHATIDIC ACID; ALBUMIN DIALYSIS; UNKNOWN ORIGIN; LIVER; ITCH Multiple languages Gastroenterology & Hepatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48242