Evaluation of serum percent trisialotransferrin as potential predictive biomarker of hepatocellular dedifferentiation in chronic liver disease

• Published in: Clinica chimica acta 2009-05, Vol.403 (1), p.188-193
• Main Authors: Gressner, Olav A., Jafari, Shadi, Erkens, Manfred, Gao, Chunfang, Stanzel, Sven, Gressner, Axel M.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biomarkers - blood; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - pathology; Case-Control Studies; CDT; Cell Dedifferentiation; Chronic Disease; Continental Population Groups; Female; Hepatocellular carcinoma; Hepatocytes - pathology; Humans; Liver Cirrhosis - blood; Liver Cirrhosis - pathology; Liver Diseases - blood; Liver Diseases - pathology; Liver fibrosis; Male; Middle Aged; Protein Isoforms - blood; Sialoglycoproteins - blood; Transferrin - analogs & derivatives; Trisialotransferrin
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2009.02.017

Chronic hepatitis induced liver fibrogenesis is characterized by epithelial-to-mesenchymal transition of liver parenchymal cells (hepatocytes) to fibroblast (-like cells), i.e. increasing hepatocellular dedifferentiation, ultimatively leading to the development of hepatocellular carcinoma (HCC). Up to now the spectrum of valid serum biomarkers for this process of hepatocellular dedifferentiation is very limited. We therefore investigated the dynamics of alterations in the serum transferrin isoform pattern in the pathogenetic sequence from liver fibrosis to hepatocellular carcinoma, to evaluate the suitability of one of the isoforms as potential biomarker for hepatocellular dedifferentiation in chronic liver disease. Our data on 252 patients with hepatitis C virus (HCV) induced fibrogenic liver disease and on 43 patients with HCV induced HCC demonstrate a dynamic alteration of serum % trisialotransferrin levels in the pathogenetic sequence from early stage hepatic fibrosis to fully developed hepatocellular carcinoma, whereas serum % di- and pentasialotransferrin values seem not to be affected. We show that patients with early stage fibrosis (METAVIR stage F1) and weak fibrogenic activitiy (METAVIR grade A1) display significantly lower values of serum % trisialotransferrin compared to healthy controls, and that serum % trisialotransferrin values increased steadily parallel to an increase of fibrotic stage and grade, respectively, while finally exceeding normal values in those patients with hepatocellular carcinoma. These findings propose a possible diagnostic value of serum % trisialotransferrin concentrations in the pathogenesis of hepatocellular dedifferentiation and the use of this parameter as possible predictive tumor marker in patients with chronic liver disease. Monitoring the pattern of transferrin bound sialic acid residues may thus be a helpful tool in assessing the risk of malignant degeneration in patients with chronic fibrogenic liver disease.