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

Manuela Neuman, Paul Angulo, Izabella Malkiewicz, Roberta Jorgensen, Neil Shear, E. Rolland Dickson, Julia Haber, Gady Katz, Keith Lindor

Research output: Contribution to journalArticlepeer-review

132 Scopus citations


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 (TGF-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.

Original languageEnglish (US)
Pages (from-to)196-202
Number of pages7
JournalJournal of Gastroenterology and Hepatology (Australia)
Issue number2
StatePublished - 2002
Externally publishedYes


  • Bile acids
  • Cytokines
  • Fibrosis
  • Hepatocytotoxicity
  • Immunomodulation
  • Primary biliary cirrhosis
  • Transforming growth factor-β
  • Tumor necrosis factor-α
  • Ursodeoxycholic acid

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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