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PRIMARY SCLEROSING CHOLANGITIS

Better end points needed in primary sclerosing cholangitis trials

Nature Reviews Gastroenterology & Hepatology (2019) | Download Citation

A new study of a fibroblast growth factor 19 analogue in patients with primary sclerosing cholangitis (PSC) provides provocative results. The data challenge alkaline phosphatase levels as the appropriate surrogate end point in PSC trials and highlight alternatives, urging efforts to identify better clinical end points for this disease.

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References

  1. 1.

    Degirolamo, C., Sabbà, C. & Moschetta, A. Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23. Nat. Rev. Drug Discov. 15, 51–69 (2016).

  2. 2.

    Karlsen, T. H. et al. Primary sclerosing cholangitis – a comprehensive review. J. Hepatol. 67, 1298–1323 (2017).

  3. 3.

    Zhou, M. et al. Separating tumorigenicity from bile acid regulatory activity for endocrine hormone FGF19. Cancer Res. 74, 3306–3316 (2014).

  4. 4.

    Zhou, M. et al. Engineered fibroblast growth factor 19 reduces liver injury and resolves sclerosing cholangitis in Mdr2-deficient mice. Hepatology 63, 914–929 (2016).

  5. 5.

    Hirschfield, G. M. et al. Effect of NGM282, a FGF19 analogue, in primary sclerosing cholangitis: a multicentre, randomized, double-blind, placebo-controlled phase 2 trial. J. Hepatol. https://doi.org/10.1016/j.jhep.2018.10.035 (2018).

  6. 6.

    Ponsioen, C. Y. et al. Surrogate endpoints for clinical trials in primary sclerosing cholangitis: review and results from an International PSC Study Group consensus process. Hepatology 63, 1357–1367 (2016).

  7. 7.

    Cheung, A. C. et al. Emerging pharmacologic therapies for primary sclerosing cholangitis. Curr. Opin. Gastroenterol. 33, 149–157 (2017).

  8. 8.

    Fickert, P. et al. norUrsodeoxycholic acid improves cholestasis in primary sclerosing cholangitis. J. Hepatol. 67, 549–558 (2017).

  9. 9.

    Trivedi, P. J. et al. Vascular adhesion protein-1 is elevated in primary sclerosing cholangitis, is predictive of clinical outcome and facilitates recruitment of gut-tropic lymphocytes to liver in a substrate-dependent manner. Gut 67, 1135–1145 (2018).

  10. 10.

    Pinzani, M. & Luong, T. V. Pathogenesis of biliary fibrosis. Biochim. Biophys. Acta Mol. Basis Dis. 1864, 1279–1283 (2018).

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Affiliations

  1. Division of Gastroenterology and Center for Autoimmune Liver Diseases, San Gerardo Hospital, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy

    • Alessio Gerussi
    •  & Pietro Invernizzi

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  1. Search for Alessio Gerussi in:

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Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Pietro Invernizzi.

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DOI

https://doi.org/10.1038/s41575-019-0110-5

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