Circulating fibronectin isoforms predict the degree of fibrosis in chronic hepatitis C

Abstract

Objective. Hepatic stellate cells only produce fibronectin isoforms in disease states. The isoform-defining domains can be detected in the blood circulation. This study examines whether circulating levels of fibronectin isoforms show a relationship with liver fibrosis on histology in patients with chronic hepatitis C. Material and methods. In a prospective study, 50 patients with chronic hepatitis C who underwent a liver biopsy were compared to 50 matched controls and 35 patients with other liver conditions. Results. Circulating levels of the fibronectin isoforms were significantly higher in patients with chronic hepatitis C compared to healthy controls [oncofetal fibronectin (oFN) 2.45 ± 0.17 versus 1.76 ± 0.16 mg/l, P < 0.005; extra domain-A (EDA) 1.05 ± 0.06 versus 0.86 ± 0.06 mg/l, P < 0.05; and extra domain-B (EDB) 14.55 ± 0.74 versus 9.31 ± 0.58 mg/l, P < 0.001], even though total fibronectin was lower (198.9 ± 3.5 versus 343.6 ± 14.5 mg/l, P < 0.001). A correlation with the fibrosis score was found for both oFN (r = 0.46, P < 0.005) and EDA (r = 0.51, P < 0.001). The combination of an elevation in both markers (oFN and EDA) in the upper quartile was associated with a specificity of > 99% for predicting significant fibrosis (stages 2–4) and 95% for predicting advanced fibrosis (stages 3–4). A combination of decreased values in the lowest tertile for both markers had a specificity of 94% for excluding significant fibrosis. Based on these findings, 30% of the patients scheduled for a liver biopsy could be correctly classified as having or not having significant fibrosis. The remainder would have to proceed with a biopsy. Conclusion. Circulating fibronectin isoforms produced by activated stellate cells represent a viable marker for the presence of significant fibrosis or a lack thereof.

Key Words::

• Chronic hepatitis C
• fibronectin
• fibrosis
• isoform
• liver biopsy
• stellate cell

Acknowledgements

We thank Reinhard Faessler and Stefan Meuer for their continued support. This work was supported by the Max-Planck Society (N. J. H. and I. A. N.), the research fund of the Faculty of Medicine at Mannheim (P.F., C. B., C. A., A. F. and M.V. S.) and the University of Heidelberg (I. A. N.). The authors report no conflicts of interest.