Clinicopathological characterization of prion: a novel marker of activatedhuman hepatic stellate cells

Background/Aims: We recently demonstrated prion as a new marker for hepatic stellate cell activation in rats. Here, we have examined prion expression in normal and diseased human livers. Methods: Prion expression was examined at protein level by immunohistochemi stry and at mRNA level by in situ hybridization. Results: While normal livers were negative for prion, all liver specimens b ut one from patients with chronic liver disease were positively stained. In chronic hepatitis, prion protein expression was found not only in the sinu soidal lining cells within the lobules but also in mesenchymal cells in exp anded portal tracts. In alcoholic liver disease, prion-positive cells were found mainly in the areas of alcoholic hepatitis. Immuno-electronmicroscopy revealed that prion-positive cells were activated stellate cells. In situ hybridization demonstrated that the distribution of prion mRNA is similar t o that of prion protein. In chronic hepatitis, the number of prion-positive cells correlated with the grade of activity but not with the stage of fibr osis, In alcoholic Fiver disease, levels of prion protein expression were s ignificantly increased in the presence of alcoholic hepatitis. Conclusion: Prion as a novel marker of activated stellate cells correlates well with disease activity in human chronic liver diseases.