Author(s): Cheung KJ, Tilleman K, Deforce D, Colle I, Moreno C,
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Abstract BACKGROUND: Liver biopsy is an imperfect standard for the assessment of chronic hepatitis C liver fibrosis. In this study, the diagnostic role of proteome-derived protein markers and the usefulness of a protein-based index were assessed. METHODS: Characteristics, clinical biochemistry, and protein markers of patients with chronic hepatitis C from a study (n=62) and validation group (n=73) were statistically assessed according to fibrosis severity. Multivariate models were built using linear discriminant analysis for the prediction of minor fibrosis (F0-F1), moderate fibrosis (F2-F3), and cirrhosis (F4). The best model was validated and diagnostic performance was compared with the aspartate aminotransferase-to-platelet ratio index based on their receiver operator characteristic curves. RESULTS: Statistical analysis resulted in significant outcomes for both clinical and protein markers. The best multivariate model was based on four protein markers: α-2-macroglobulin (A2M), haptoglobin, hemopexin, and galectin-3-binding protein. A2M and hemopexin were the primary predictors according to this model. A novel index A2M/hemopexin [fibrosis-protein (FI-PRO) index] showed a diagnostic performance rate of 0.80-0.92 for the detection of significant fibrosis (F2-F4) and advanced fibrosis (F3-F4) in the validation group, which was better compared with aspartate aminotransferase-to-platelet ratio index. FI-PRO had an overall positive predictive value of 86\% for significant fibrosis and a negative predictive value of at least 90\% for advanced fibrosis. CONCLUSION: Proteome-derived protein markers were successfully implemented in clinical diagnosis of hepatitis C fibrosis, which resulted in the FI-PRO index. The efficiency and usability of FI-PRO should be validated in large-scale, prospective studies.
This article was published in Eur J Gastroenterol Hepatol
and referenced in Journal of Proteomics & Bioinformatics