In situ expression of transforming growth factor-beta 1-3, latent transforming growth factor-beta binding protein and tumor necrosis factor-alpha in liver tissue from patients with chronic hepatitis C

Background: The mechanisms determining liver damage in chronic hepatitis C remain unclear. The aim was to evaluate the in situ expression of transform ing growth factor beta (TGF-beta) and tumor necrosis factor-a (TNF-alpha), two key cytokines implicated as important pathogenic mediators in the devel opment of liver fibrosis. Methods: In situ expression of TNF-alpha and of T GF-beta isoforms 1-3, and its transport protein latent TGF-beta binding pro tein (LTBP), was determined by immunohistochemistry in 9 untreated patients with chronic hepatitis C infection and in 6 controls without liver disease . In addition, TGF-beta1 expression was analyzed in 10 HCV patients before and after treatment with interferon-alpha alone, or in combination with rib avirin. Results: Liver biopsies from HCV patients showed positive staining fur TGF-beta1-3 isoforms and LTBP, and to a lesser degree for TNF-alpha in areas with inflammation and fibrosis. Normal central liver showed no positi ve staining. TGF-beta1 expression before treatment, quantified by morphomet ric analysis, did not differ between non-responders and sustained responder s. In patients responding to therapy, TGF-beta1 expression decreased in par allel with histological improvement, while no difference in TGF-PI expressi on was seen before and after treatment in non-responders. Conclusion: These results suggest that TNF-alpha and all three isoforms of TGF-beta are invo lved in the pathogenesis of HCV related liver disease, and that treatment l eading to eradication of the virus affects the expression of TGF-beta1.