TGF-beta1 mRNA expression in liver biopsy specimens and TGF-beta1 serum levels in patients with chronic hepatitis C before and after antiviral therapy

J Clin Pharm Ther. 2005 Jun;30(3):271-7. doi: 10.1111/j.1365-2710.2005.00644.x.

Abstract

Background and objective: Transforming growth factor (TGF)-beta1 is the best-characterized profibrogenic cytokine. TGF-beta1 increases the production of extracellular matrix proteins and their receptors and inhibits the synthesis of matrix degrading proteolytic enzymes. We undertook this study to simultaneously evaluate the effect of interferon alpha 2b plus ribavirin therapy on TGF-beta1 daily serum levels and on mRNA TGF-beta1 expression in liver biopsy specimens from 60 patients with chronic hepatitis C.

Methods: Serum levels of TGF-beta1 were measured by ELISA. The levels of the RNAs in liver biopsy specimens were measured by quantitative reverse transcriptase polymerase chain reaction. After treatment, patients were divided into two groups: 34 responders [undetectable hepatitis C virus (HCV)-RNA, normal ALT levels, decrease in histology activity index compared with pretreatment liver biopsy] and 26 non-responders (detectable HCV-RNA, elevated ALT levels, no decrease in the histology activity index).

Results and discussion: In patients with hepatitis C, the 'responders' to the antiviral treatment showed significant decreases in both mean daily serum TGF-beta1 levels and mRNA TGF-beta1 expression in the liver biopsy specimens. The 'non-responders' serum TGF-beta1 concentrations did not change significantly, but the mRNA TGF-beta1 expression did.

Conclusion: Both serum TGF-beta1 concentration and mRNA TGF-beta1 expression in liver biopsy specimens may be useful as prognostic markers in patients with hepatitis C undergoing antiviral therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / metabolism
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Liver / metabolism*
  • Male
  • RNA, Messenger / antagonists & inhibitors*
  • RNA, Messenger / metabolism
  • Recombinant Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribavirin / therapeutic use*
  • Transforming Growth Factor beta / antagonists & inhibitors*
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta1

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Messenger
  • Recombinant Proteins
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Ribavirin