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Invasive liver biopsy is the current method for the assessment of liver fibrosis. In search of noninvasive alternatives, galectin-3-binding protein (G3BP) was introduced as a candidate-marker of hepatitis C-related fibrosis based on serum proteomics. We investigated the role of G3BP as a single-marker of significant fibrosis and cirrhosis by serology and histology and studied the effect of glycosylation on antibody-affinity in hepatitis C and alcoholic cirrhosis.Sera and available biopsies of hepatitis C patients with various fibrosis-grades and patients with alcoholic cirrhosis were used for G3BP-measurements by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. Glycosylation-effect was analyzed by western blot. Data was analyzed in accordance to fibrosis.G3BP-levels (mean±standard deviation) were increased during cirrhosis (22.7±10.1 μg/ml) compared to mild (11.3±6.4 μg/ml) and moderate fibrosis (13.4±8.3 μg/ml) (P<0.001; P=0.004, respectively). Receiver operator characteristic curves showed areas under the curve of 0.68, 0.75 and 0.81 for detection of significant fibrosis, severe fibrosis, and cirrhosis, respectively. Similar findings in hepatic G3BP expression were obtained, in which cirrhosis was associated with diffuse, parenchymal expression (P=0.002). The observed difference between hepatitis C and alcoholic cirrhosis (13.5±9.0 μg/ml) (P=0.009) could not be explained by glycosylation.Our recent findings confirm our initial proteome results on serological and histological level as well as the role of G3BP as a marker of hepatitis C-related fibrosis, especially cirrhosis. Implication of this protein in future multi-marker study should be considered.