Hepatic Stellate Cells in Hepatitis C Patients: Relationship With the Development of Interstitial Fibrosis in Renal Allografts

Abstract

The aim of this study was twofold; first, we evaluated the influence of hepatitis C virus (HCV) and iron deposition on hepatic stellate cells (HSCs), and second, we determined the influence of HSCs on the development of interstitial fibrosis (IF) in renal allografts. Thirty chronic HCV positive patients bearing renal allografts underwent liver biopsies, which were scored for iron deposition and the number of HSCs. We evaluated the density of tumor necrosis factor-alpha (TNF-alpha) in liver biopsies and the expression of transforming growth factor-beta (TGF-beta) on tubules of renal allografts from the same patients. We examined the development of IF in renal allografts at 12 and 24 months after the reference biopsy. The density of HSCs was significantly greater among patients with compared with those without iron deposits (P < .01). TNF-alpha expression was localized mainly to liver sinusoidal cells; in some cases, it was also expressed in hepatocytes. Patients with higher-grade TNF-alpha expression in the liver showed higher-grade alpha-smooth muscle antibody (alpha-SMA)-positive HSCs (P < .001). In parallel, an increasing amount of HSCs in the liver increased the incidence of IF in the renal allograft at 12 (P < .01) and 24 (P < .01) months after the reference biopsy. In addition, the expression of TGF-beta on renal allograft tubules were increased with greater grades of alpha-SMA-positive HSCs in liver (P < .01). In conclusion, HCV infection seemed to trigger the development of IF in renal allografts by augmenting TGF-beta secretion through activation of HSC.