Clinicopathological characterization of prion: a novel marker of activated human hepatic stellate cells.
OBJECTIVE
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 immunohistochemistry and at mRNA level by in situ hybridization.


RESULTS
While normal livers were negative for prion, all liver specimens but one from patients with chronic liver disease were positively stained. In chronic hepatitis, prion protein expression was found not only in the sinusoidal lining cells within the lobules but also in mesenchymal cells in expanded portal tracts. In alcoholic liver disease, prion-positive cells were found mainly in the areas of alcoholic hepatitis. Immunoelectronmicroscopy revealed that prion-positive cells were activated stellate cells. In situ hybridization demonstrated that the distribution of prion mRNA is similar to 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 fibrosis. In alcoholic liver disease, levels of prion protein expression were significantly increased in the presence of alcoholic hepatitis.


CONCLUSIONS
Prion as a novel marker of activated stellate cells correlates well with disease activity in human chronic liver diseases.
Kitada
T
T
Third Department of Internal Medicine, Osaka City University Medical School, Japan.
Seki
S
S
Ikeda
K
K
Nakatani
K
K
Sakaguchi
H
H
Kawada
N
N
Kadoya
H
H
Kaneda
K
K
D015415:Biomarkers; D002908:Chronic Disease; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D017403:In Situ Hybridization; D008099:Liver / Q000737:chemistry* / Q000166:cytology*; D008107:Liver Diseases / Q000209:etiology; D016253:Microscopy, Immunoelectron; D011328:Prions / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D011328:Prions; D012333:RNA, Messenger