Henderson, A.; Bigley, G.; Warnes, T.W.; McMahon, R.F.T.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA106
Academic Journal
The pathogenesis of hepatitis C virus (HCV) induced chronic liver disease is incompletely understood, with two main processes involved including immune mediated damage and direct cytopathic viral effects. Steatosis is thought to be a cytopathic manifestation and has been shown to be an independent risk factor for the development of fibrosis. In patients with steatosis and steatohepatitis, it has been shown that Kupffer cells are aggregated in the perivenular region. In view of the observation that 50% of patients with chronic HCV infection have steatosis, we have examined liver biopsies from 25 HCV infected individuals and control biopsies from HBV and alcohol induced liver disease for the expression of CD68, a marker oF Kupffer cells, using a standard immunohistochemiocal method. The zonal distribution of CD68 positive cells was assessed and compared with the extent of steatosis, categorised into mild, moderate and severe degrees, and with the Ishak necroinflammatory activity. In chronic HCV biopsies, there was a trend towards perivenulor distribution of CD68 positivity, particularly with increasing severity of steatosis. Biopsies showing established cirrhosis were excluded from the study and potential confounding factors of comorbidity were taken into consideration. No differences were observed related to alcohol consumption (taking 140g/week as a cut-off), obesity (BMI > 30 kg/m²) or Ishak necroinflammatory activity. The perivenular distribution of CD68 positive Kupffer cells suggests that recruitment of Kupffer cells may play a part in the pathogenesis of HCV related liver disease, through the release of TNF-α and activation of other cytokines important in the development oF inflammation and fibrosis. This zonal Iocalisation may provide insights into the mechanisms responsible For progression of chronic HCV infection, especially in those patients with significant levels of steatosis. Further work is required in this area with regard to the...


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