title: Clinical significance of connective tissue growth factor in hepatitis B virus-induced hepatic fibrosis.
abstract: OBJECTIVE
  To determine the utility of connective tissue growth factor (CCN2/CTGF) for assessing hepatic fibrosis in hepatitis B virus (HBV)-induced chronic liver diseases (CLD-B).
  
  
  METHODS
  Enzyme-linked immunosorbent assay was used to measure CCN2 in sera from 107 patients with chronic hepatitis B (CHB) and 39 patients with HBV-induced active liver cirrhosis and 30 healthy individuals. Liver samples from 31 patients with CHB, 8 patients with HBV-induced liver cirrhosis and 8 HBV carriers with normal liver histology were examined for transforming growth factor β-1 (TGF-β1) or CCN2 mRNA levels by in situ hybridization, and computer image analysis was performed to measure integrated optimal density (IOD) of CCN2 mRNA-positive cells in liver tissues. Histological inflammation grading and fibrosis staging were evaluated by H and E staining and Van Gieson's method.
  
  
  RESULTS
  Serum CCN2 concentrations were, respectively, 4.0- or 4.9-fold higher in patients with CHB or active liver cirrhosis as compared to healthy individuals (P < 0.01). There was good consistency between the levels of CCN2 in sera and CCN2 mRNA expression in liver tissues (r = 0.87, P < 0.01). The levels of CCN2 in sera were increased with the enhancement of histological fibrosis staging in patients with CLD-B (r = 0.85, P < 0.01). Serum CCN2 was a reliable marker for the assessment of liver fibrosis, with areas under the receiver operating characteristic (ROC) curves (AUC) of 0.94 or 0.85 for, respectively, distinguishing normal liver controls from patients with F1 stage liver fibrosis or discriminating between mild and significant fibrosis.
  
  
  CONCLUSIONS
  Detection of serum CCN2 in patients with CLD-B may have clinical significance for assessment of severity of hepatic fibrosis.
authors.affiliation: Department of Hepatic-biliary-pancreatic Medicine, First Hospital, Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Rong-Li
authors.initials: RL
authors.lastname: Piao
authors.forename: David R
authors.initials: DR
authors.lastname: Brigstock
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.forename: Man-Li
authors.initials: ML
authors.lastname: Zhang
authors.forename: Run-Ping
authors.initials: RP
authors.lastname: Gao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D002681:China; D055513:Connective Tissue Growth Factor / Q000097:blood* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D017403:In Situ Hybridization; D008099:Liver / Q000737:chemistry* / Q000821:virology; D008103:Liver Cirrhosis / Q000097:blood* / Q000235:genetics / Q000821:virology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis; D012372:ROC Curve; D012720:Severity of Illness Index; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; C526317:CCN2 protein, human; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor