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

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 c...

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Bibliographische Detailangaben
Hauptverfasser: Hackl, Norman J. (VerfasserIn) , Bersch, Claus (VerfasserIn) , Feick, Peter (VerfasserIn) , Antoni, Christoph Helmer (VerfasserIn) , Franke, Andreas (VerfasserIn) , Singer, Manfred V. (VerfasserIn) , Nakchbandi, Inaam (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2010
In: Scandinavian journal of gastroenterology
Year: 2010, Jahrgang: 45, Heft: 3, Pages: 349-356
ISSN:1502-7708
DOI:10.3109/00365520903490606
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3109/00365520903490606
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Verfasserangaben:Norman J. Hackl, Claus Bersch, Peter Feick, Christoph Antoni, Andreas Franke, Manfred V. Singer & Inaam A. Nakchbandi

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520 |a 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. 
650 4 |a Adult 
650 4 |a Biomarkers 
650 4 |a Biopsy, Needle 
650 4 |a Case-Control Studies 
650 4 |a Cross-Sectional Studies 
650 4 |a Female 
650 4 |a Fibronectins 
650 4 |a Hepatic Stellate Cells 
650 4 |a Hepatitis C, Chronic 
650 4 |a Humans 
650 4 |a Liver Cirrhosis 
650 4 |a Male 
650 4 |a Middle Aged 
650 4 |a Predictive Value of Tests 
650 4 |a Protein Isoforms 
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