Pruritus in cholestasis: Facts and fiction

Authors

  • Ulrich Beuers,

    Corresponding author
    1. Tytgat Institute for Liver and Intestinal Research, Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, The Netherlands
    • Address reprint requests to: Ulrich Beuers, M.D., Department of Gastroenterology & Hepatology, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, G4-216, University of Amsterdam, P.O. Box 22600, NL-1100 DD Amsterdam, The Netherlands. E-mail: u.h.beuers@amc.uva.nl; fax: +31-20-566 95 82.

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  • Andreas E. Kremer,

    1. Tytgat Institute for Liver and Intestinal Research, Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, The Netherlands
    2. Department of Medicine 1, Friedrich-Alexander University of Erlangen-Nuremberg, Germany
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  • Ruth Bolier,

    1. Tytgat Institute for Liver and Intestinal Research, Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, The Netherlands
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  • Ronald P.J. Oude Elferink

    1. Tytgat Institute for Liver and Intestinal Research, Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, The Netherlands
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  • Potential conflict of interest: Nothing to report.

Abstract

Pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, or hereditary pediatric cholestatic disorders and may accompany, although less frequently, many other liver diseases. Recent findings indicate that lysophosphatidic acid (LPA), a potent neuronal activator, and autotaxin (ATX; ectonucleotide pyrophosphatase/phosphodiesterase 2), the enzyme which forms LPA, may form a key element of the long-sought pruritogenic signaling cascade in cholestatic patients suffering from itch. Serum ATX, but no other pruritogen candidate studied so far, correlates with pruritus intensity and responds to therapeutic interventions. In this comprehensive review, we provide a short update on actual insights in signal transmission related to pruritus and discuss pruritogen candidates in cholestasis. We also summarize evidence-based and guideline-approved as well as experimental therapeutic approaches for patients suffering from pruritus in cholestasis. (Hepatology 2014;60:399–407)

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