Role of fibrogenic markers in chronic hepatitis C and associated hepatocellular carcinoma

• Published in: Molecular biology reports 2012-06, Vol.39 (6), p.6843-6850
• Main Authors: El-Bassiouni, N. E, Nosseir, M. M. F, Madkour, M. E, Zoheiry, M. M. K, Bekheit, I. W, Ibrahim, R. A, Ibrahim, I. M, El Bassiouny, A. E
• Format: Article
• Language: English
• Subjects: Adult; Animal Anatomy; Animal Biochemistry; Biomarkers; Biomarkers - blood; Biomarkers - metabolism; Biomedical and Life Sciences; Biopsy; Cancer; carcinogenesis; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - virology; Case-Control Studies; Cell Transformation, Neoplastic; Cholecystectomy; chronic hepatitis C; Chronic illnesses; Cirrhosis; Connective tissue growth factor; Connective Tissue Growth Factor - metabolism; Data processing; Extracellular Matrix - metabolism; Female; Fibrosis; Hepatitis; Hepatitis C; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - metabolism; Hepatitis C, Chronic - pathology; Hepatocellular carcinoma; hepatoma; Histology; Humans; Hyaluronic acid; Hyaluronic Acid - blood; immunohistochemistry; Laparoscopy; Life Sciences; liver; liver cirrhosis; Liver Cirrhosis - metabolism; Liver Cirrhosis - pathology; Liver Cirrhosis - virology; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Liver Neoplasms - virology; Male; Middle Aged; monitoring; Morphology; patients; Platelet-derived growth factor; Platelet-Derived Growth Factor - metabolism; Precancerous Conditions - metabolism; Precancerous Conditions - pathology; Precancerous Conditions - virology; risk; Transformation; Transforming Growth Factor beta1 - metabolism; Transforming growth factor- beta 1; Tumorigenesis; Young Adult
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-012-1509-z

Detection and follow up of fibrogenesis in chronic hepatitis C (CHC) is mandatory for early treatment and risk stratification. The current study included 120 patients with CHC, of whom 30 had liver cirrhosis (LC) and 30 had hepatocellular carcinoma (HCC). 15 wedge liver biopsies, taken during laparoscopic cholecystectomy, were included as normal controls. Cases were subjected to laboratory investigations, serologic markers for viral hepatitis and assessment of circulating levels of hyaluronic acid (HA) and platelet-derived growth factor (PDGF). Immunohistochemical expression of connective tissue growth factor (CTGF), PDGF and transforming growth factor-β1 (TGF-β1) was also carried out. A significant increase (p < 0.01) in serum HA was noticed in CHC, LC and HCC compared to controls. Although, a significant decrease in serum PDGF was detected in CHC and LC compared to controls, HCC values were comparable. A significant up-regulation of CTGF was detected in CHC, LC and HCC (p < 0.01) in contrast to its limited mild expression in normal livers. Intense PDGF positive staining was noticed in CHC, LC and HCC compared to scattered faint expression in controls. The significant expression and marked intensity of PDGF staining matched the progress to tumorigenesis. A positive TGF-β1 immunostaining was also noticed in CHC, LC and HCC. An intense and extensive cytoplasmic expression of TGF-β1 was encountered in patients with LC revealing that CTGF, PDGF and TGF-β1 act synergistically in LC. Data revealed that HA and CTGF may be implicated as important diagnostic parameters for assessment of hepatic fibrosis and PDGF for monitoring malignant transformation in CHC.