Hepatic stellate cell activation and liver fibrosis are associated with necroinflammatory injury and Th1-like response in chronic hepatitis C

Background/Aims: The involvement of a direct viral cytopathic effect or an immune-mediated mechanism in the progression of hepatic damage in chronic h epatitis C is controversial. The type of immune response is itself a matter of controversy, and histological data are lacking. The aim of this study w as to identify the factors associated with the progression of liver injury in 30 HCV/RNA-positive untreated patients with chronic hepatitis. Methods. Necroinflammatory and architectural damage were evaluated using Ishak's sco re. Activated hepatic stellate cells (HSC) were visualized by immunohistoch emistry for ct-smooth muscle actin (alpha SMA) and quantitated by morphomet ry. Plasma HCV/RNA was evaluated using a competitive RT-PCR method. To stud y the type of immune response involved in the progression of liver injury, interferon gamma (IFN gamma)-positive cells (as expression of a Th1-like re sponse) were evaluated by immunohistochemistry and quantitated by morphomet ry. Results HSC were mostly detected close to areas of lobular necroinflamm ation or lining fibrotic septa. The alpha SMA- and Sirius Red-positive pare nchyma correlated significantly with necroinflammatory and architectural sc ores. IFN gamma-positive cells were detected in periportal areas associated with the inflammatory infiltrates and significantly correlated with archit ectural damage. No relationship was found between the histological features of liver injury and viral load. Conclusions: HSC activation and progressio n of liver injury are unrelated to viral load but associated with a Th1-lik e response, a plausible target for the treatment of chronic hepatitis C.