Premium
Quantitative analysis of transforming growth factor β1 messenger RNA in the liver of patients with chronic hepatitis C: Absence of correlation between high levels and severity of disease
Author(s) -
Roulot Dominique,
Durand Hervé,
Coste Thierry,
Rautureau Jacques,
Strosberg A. Donny,
Benarous Richard,
Marullo Stefano
Publication year - 1995
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840210206
Subject(s) - messenger rna , transforming growth factor , gdf15 , cytokine , hepatitis c virus , fibrosis , medicine , liver disease , interferon , biology , procollagen peptidase , hepatitis c , chronic liver disease , immunology , virus , cirrhosis , gene , biochemistry
Transforming growth factor β1 (TGFβ1) is a cytokine involved in liver fibrogenesis. Previous semiquantitative studies of patients with chronic viral hepatitis showed that liver TGFβ1 messenger RNA (mRNA) was increased, compared with normal controls and with patients with chronic hepatitis C virus (HCV) infection who responded favorably to interferon alfa (IFNα) treatment. To evaluate its potential prognostic significance, we measured liver TGFβ1 mRNA, using a new competitive reverse gene amplification assay, in a total of 35 patients with chronic HCV. This technique was reproducible and sensitive; we could measure as few as 5,000 molecules of TGFβ1 mRNA per microgram of total liver RNA. In patients with chronic HCV, the mean level of TGFβ1 mRNA was 200‐fold higher than in controls. However, no correlation could be found between TGFβ1 mRNA and either the biological (serum amino‐terminal peptide of type III procollagen) and histological (Knodell scores) indices of liver fibrosis or a favorable response to IFNα therapy. In 9 patients, second liver specimens were obtained after treatment; in most cases, TGFβ1 mRNA levels and hepatic histological findings varied in parallel. These data are consistent with the hypothesis that TGFβ1 plays a role in stimulating liver fibrogenesis during chronic HCV, despite the lack of prognostic value of TGFβ1 mRNA levels measured before treatment. Additional biological parameters, such as the processing of the TGFβ1 precursor to its active form or the respective levels of the three TGFβ receptor subtypes within the liver, could explain the lack of correlation between TGFβ1 mRNA and indices of liver fibrogenesis. (H EPATOLOGY 1995;21:298–304.)