Connective tissue growth factor, steatosis and fibrosis in patients with chronic hepatitis C

Caroline Hora, Francesco Negro, Giacchino Leandro, Carl M. Oneta, Laura Rubbia-brandt, Beat Muellhaupt, Beat Helbling, Raffaele Malinverni, Jean Jacques Gonvers, Jean François Dufour

Research output: Contribution to journalArticle

Abstract

Background/Aim: 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.

Original languageEnglish
Pages (from-to)370-376
Number of pages7
JournalLiver International
Volume28
Issue number3
DOIs
Publication statusPublished - Mar 2008

Keywords

  • Hepatitis C virus
  • Insulin resistance
  • Leptin
  • Liver fibrogenesis

ASJC Scopus subject areas

  • Hepatology

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    Hora, C., Negro, F., Leandro, G., Oneta, C. M., Rubbia-brandt, L., Muellhaupt, B., Helbling, B., Malinverni, R., Gonvers, J. J., & Dufour, J. F. (2008). Connective tissue growth factor, steatosis and fibrosis in patients with chronic hepatitis C. Liver International, 28(3), 370-376. https://doi.org/10.1111/j.1478-3231.2007.01608.x