title: Connective tissue growth factor, steatosis and fibrosis in patients with chronic hepatitis C.
abstract: OBJECTIVE
  Both steatosis and insulin resistance have been linked to accelerated fibrosis in chronic hepatitis C. Connective tissue growth factor (CTGF) plays a major role in extracellular matrix production in fibrotic disorders including cirrhosis, and its expression is stimulated in vitro by insulin and glucose. We hypothesized that CTGF may link steatosis, insulin resistance and fibrosis.
  
  
  METHODS
  We included 153 chronic hepatitis C patients enrolled in the Swiss Hepatitis C Cohort Study and for whom a liver biopsy and plasma samples were available. CTGF expression was assessed quantitatively by immunohistochemistry. In 94 patients (57 with genotypes non-3), plasma levels of glucose, insulin and leptin were also measured. CTGF synthesis was investigated by immunoblotting on LX-2 stellate cells.
  
  
  RESULTS
  Connective tissue growth factor expression was higher in patients with steatosis (P=0.039) and in patients with fibrosis (P=0.008) than those without these features. CTGF levels were neither associated with insulinaemia or with glycaemia, nor with inflammation. By multiple regression analysis, CTGF levels were independently associated with steatosis, a past history of alcohol abuse, plasma leptin and HCV RNA levels; when only patients with genotypes non-3 were considered, CTGF levels were independently associated with a past history of alcohol abuse, plasma leptin levels and steatosis. Leptin stimulated CTGF synthesis in LX-2 cells.
  
  
  CONCLUSIONS
  In patients with chronic hepatitis C and steatosis, CTGF may promote fibrosis independently of inflammation. CTGF may link steatosis and fibrosis via increased leptin levels.
authors.affiliation: Department of Clinical Pharmacology, University of Bern, Bern, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hora
authors.forename: Francesco
authors.initials: F
authors.lastname: Negro
authors.forename: Giacchino
authors.initials: G
authors.lastname: Leandro
authors.forename: Carl M
authors.initials: CM
authors.lastname: Oneta
authors.forename: Laura
authors.initials: L
authors.lastname: Rubbia-Brandt
authors.forename: Beat
authors.initials: B
authors.lastname: Muellhaupt
authors.forename: Beat
authors.initials: B
authors.lastname: Helbling
authors.forename: Raffaele
authors.initials: R
authors.lastname: Malinverni
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Gonvers
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dufour
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D055513:Connective Tissue Growth Factor; D005234:Fatty Liver / Q000209:etiology*; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D020738:Leptin / Q000097:blood; D008103:Liver Cirrhosis / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D013557:Switzerland
chemical_list: D001786:Blood Glucose; C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D055513:Connective Tissue Growth Factor