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

Abstract

Transforming growth factor beta 1 (TGF beta 1) is a cytokine involved in liver fibrogenesis. Previous semiquantitative studies of patients with chronic viral hepatitis showed that liver TGF beta 1 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 (IFN alpha) treatment. To evaluate its potential prognostic significance, we measured liver TGF beta 1 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 TGF beta 1 mRNA per microgram of total liver RNA. In patients with chronic HCV, the mean level of TGF beta 1 mRNA was 200-fold higher than in controls. However, no correlation could be found between TGF beta 1 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 IFN alpha therapy. In 9 patients, second liver specimens were obtained after treatment; in most cases, TGF beta 1 mRNA levels and hepatic histological findings varied in parallel. These data are consistent with the hypothesis that TGF beta 1 plays a role in stimulating liver fibrogenesis during chronic HCV, despite the lack of prognostic value of TGF beta 1 mRNA levels measured before treatment.(ABSTRACT TRUNCATED AT 250 WORDS)