Prospective evaluation of ursodeoxycholic acid withdrawal in patients with primary sclerosing cholangitis

Authors

  • Ewa Wunsch,

    1. Liver Research Laboratories, Pomeranian Medical University, Szczecin, Poland
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  • Jocelyn Trottier,

    1. Laboratory of Molecular Pharmacology, CHU-Québec and Faculty of Pharmacy, Laval University, Québec, Québec, Canada
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  • Malgorzata Milkiewicz,

    1. Medical Biology Laboratory, Pomeranian Medical University, Szczecin, Poland
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  • Joanna Raszeja-Wyszomirska,

    1. Liver Research Laboratories, Pomeranian Medical University, Szczecin, Poland
    2. Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery of the Medical University of Warsaw, Warsaw, Poland
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  • Gideon M. Hirschfield,

    1. Center for Liver Research, National Institute of Health Research (NIHR) Biomedical Research Unit, University of Birmingham, Birmingham, UK
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  • Olivier Barbier,

    1. Laboratory of Molecular Pharmacology, CHU-Québec and Faculty of Pharmacy, Laval University, Québec, Québec, Canada
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  • Piotr Milkiewicz

    Corresponding author
    1. Liver Research Laboratories, Pomeranian Medical University, Szczecin, Poland
    2. Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery of the Medical University of Warsaw, Warsaw, Poland
    • Address reprint requests to: Piotr Milkiewicz, M.D., M.R.C.P(UK)., Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha 1A, 02-097 Warsaw, Poland. E-mail: p.milkiewicz@wp.pl; fax: +48 22 599 1662.

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  • Potential conflict of interest: Nothing to report.

  • P.M. was supported by grant no. 2011/01/B/NZ5/04216 from the National Science Center in Poland. O.B. was supported by a grant from the Canadian Liver Foundation and a Canadian Institutes of Health Research salary award (New Investigator Award no. MSH95330).

  • See Editorial on Page 785

Abstract

Ursodeoxycholic acid (UDCA) is no longer recommended for management of adult patients with primary sclerosing cholangitis (PSC). We undertook a prospective evaluation of UDCA withdrawal in a group of consecutive patients with PSC. Twenty six patients, all treated with UDCA (dose range: 10-15 mg/kg/day) were included. Paired blood samples for liver biochemistry, bile acids, and fibroblast growth factor 19 (FGF19) were collected before UDCA withdrawal and 3 months later. Liquid chromatography/tandem mass spectrometry was used for quantification of 29 plasma bile acid metabolites. Pruritus and health-related quality of life (HRQoL) were assessed with a 10-point numeric rating scale, the Medical Outcomes Study Short Form-36 (SF-36), and PBC-40 questionnaires. UDCA withdrawal resulted in a significant deterioration in liver biochemistry (increase of alkaline phosphatase of 75.6%; P < 0.0001; gamma-glutamyl transpeptidase of 117.9%, P < 0.0001; bilirubin of 50.0%, P < 0.001; alanine aminotransferase of 63.9%, P < 0.005; and aspartate aminotransferase of 45.0%, P < 0.005) and increase of Mayo Risk Score for PSC (change from baseline of +0.5 point; P < 0.003). Bile acid analysis revealed a significant decrease in lithocholic acid and its derivatives after UDCA withdrawal, but no effect on concentrations of primary bile acids aside from an increased accumulation of their taurine conjugates. After UDCA removal cholestatic parameters, taurine species of cholic acid and chenodeoxycholic acid correlated with serum FGF19 levels. No significant effect on HRQoL after UDCA withdrawal was observed; however, 42% of patients reported a deterioration in their pruritus. Conclusion: At 3 months, discontinuation of UDCA in patients with PSC causes significant deterioration in liver biochemistry and influences concentrations of bile acid metabolites. A proportion of patients report increased pruritus, but other short-term markers of quality of life are unaffected. (Hepatology 2014;60:931–940)

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