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Tumor necrosis factor-α and transforming growth factor-β reflect severity of liver damage in primary biliary cirrhosis

Authors

  • MANUELA NEUMAN,

    1. Division of Clinical Pharmacology, Sunnybrook and Women’s Health Sciences Center and Department of Pharmacology, University of Toronto, Toronto, Canada and
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  • PAUL ANGULO,

    1. Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, Minnesota, United States of America
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  • IZABELLA MALKIEWICZ,

    1. Division of Clinical Pharmacology, Sunnybrook and Women’s Health Sciences Center and Department of Pharmacology, University of Toronto, Toronto, Canada and
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  • ROBERTA JORGENSEN,

    1. Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, Minnesota, United States of America
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  • NEIL SHEAR,

    1. Division of Clinical Pharmacology, Sunnybrook and Women’s Health Sciences Center and Department of Pharmacology, University of Toronto, Toronto, Canada and
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  • E ROLLAND DICKSON,

    1. Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, Minnesota, United States of America
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  • JULIA HABER,

    1. Division of Clinical Pharmacology, Sunnybrook and Women’s Health Sciences Center and Department of Pharmacology, University of Toronto, Toronto, Canada and
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  • GADY KATZ,

    1. Division of Clinical Pharmacology, Sunnybrook and Women’s Health Sciences Center and Department of Pharmacology, University of Toronto, Toronto, Canada and
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  • KEITH LINDOR

    1. Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, Minnesota, United States of America
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Manuela G Neuman, PhD, Division of Clinical Pharmacology, E-240, Sunnybrook and Women’s College Health Sciences Center, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5, Canada. Email: manuela@sten.sunnybrook.utoronto.ca

Abstract

Background and Aims The pathogenesis of primary biliary cirrhosis (PBC) is unknown. The role of cytokines such as tumor necrosis factor-α (TNF-α) and transforming growth factor-β (ΤGF-β), and the effect of ursodeoxycholic acid (UDCA) in modifying the cytokine environment in patients with PBC has remained largely unstudied. Our aims were to determine: (i) the relationship between serum levels of TNF-α and TGF-β and the severity of PBC; and (ii) the effects of UDCA therapy on TNF-α and TGF-β levels in patients with PBC.

Methods We studied 90 patients who had been treated with UDCA (53 patients) or placebo (37 patients) for 2 years as part of a randomized, double-blind, controlled trial. Patients were divided into histological stage I/II or stage III/IV disease. Serum TNF-α and TGF-β levels were quantified by enzyme-linked immunoabsorbent assay.

Results Baseline levels of TNF-α were significantly greater in patients with stage III/IV compared to stage I/II disease. After 2 years of treatment with UDCA, patients showed a significantly greater decrease in TNF-α levels and progression risk score compared to placebo-treated patients. TNF-α and TGF-β levels were significantly reduced compared to baseline levels in the UDCA-treated group after 2 years, while there was no significant change in the levels of placebo-treated patients.

Conclusions Serum TNF-α and TGF-β levels may reflect severity of disease in patients with PBC. The beneficial effects of UDCA therapy may be explained by lowering serum levels of these two cytokines.

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