Activated Hepatic Stellate Cells (Ito Cells)- Marker of Advanced Fibrosis in Chronic Viral Hepatitis C: A Pilot Study

Background & Aims: The aim of this study is to determine whether activated hepatic stellate cells (HSCs) may represent a prognostic marker of progressive liver fibrosis in chronic viral hepatitis C (VHC) before antiviral therapy. The possible correlation between HSCs immunohistochemical features, histopathological aspects and clinical data before therapy were also studied.Methods: This retrospective pilot study was conducted on 27 liver biopsies from VHC patients before antiviral therapy. HSCs's immunohistochemical analysis used the antibodies alpha-smooth muscle actin (a-SMA), glial fibrillary acidic protein (GFAP) and vinculin. We correlated immunopositive HSCs with HCV load, liver stiffness (LS), fibrosis stage and necro-inflammatory degree before treatment. Also, we assessed the association between liver fibrosis after therapy, the sustained virological response at 12 weeks after therapy (SVR 12) and the type of therapy.Results: HSCs were increased in VHC patients compared to controls, mainly in the intermediate and periportal lobular regions. a-SMA and vinculin HSCs correlated positively with fibrosis stage (p=0.044), (p=0.028). Furthermore, a-SMA and vinculin HSCs were associated with LS (p=0.027), (p=0.002) and viral load (p=0.021), (p=0.006), but not with necro-inflammation degree. GFAP HSCs inversely correlated with fibrosis stage (r=-0.475), LS (r=-0.422) and HCV load (r=-0.517), but positively with necro-inflammation degree (p=0.038). Liver fibrosis post therapy correlated positively with SVR12 (p<0.001) and the type of therapy (p=0.006) and SVR12 correlated positively with treatment's type (p=0.002).Conclusions: Activated HSCs may represent a marker of increased liver fibrosis in VHC. Different immunohistochemical markers can detect various HSCs subpopulations involved in the evolution of VHC and liver fibrosis.