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Published on: February 10, 2015
Tumor necrosis factor-alpha and transforming growth factor-beta reflect severity of liver damage in primary biliary
Manuela Neuman1, Paul Angulo, Izabella Malkiewicz
1Division of Clinical Pharmacology, Sunnybrook and Women's Health Sciences Center, University of Toronto, Toronto, Ontario, Canada. manuela@sten.sunnybrook.utoronto.ca
Background And Aims:
The pathogenesis of primary biliary cirrhosis (PBC) is unknown. The role of cytokines such as tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), 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-alpha and TGF-beta and the severity of PBC; and (ii) the effects of UDCA therapy on TNF-alpha and TGF-beta 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-alpha and TGF-beta levels were quantified by enzyme-linked immunoabsorbent assay.
Results:
Baseline levels of TNF-alpha 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-alpha levels and progression risk score compared to placebo-treated patients. TNF-alpha and TGF-beta 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-alpha and TGF-beta 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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