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Large Liver Cell Dysplasia in Hepatitis B Virus X Transgenic Mouse Liver and Human Chronic Hepatitis B Virus-Infected Liver

 Koo J.S.  ;  Seong J.K.  ;  Park C.  ;  Yu D.-Y.  ;  Oh B.-K.  ;  Oh S.H.  ;  Park Y.N. 
 INTERVIROLOGY, Vol.48(1) : 16-22, 2005 
Journal Title
Issue Date
Adult ; Animals ; Apoptosis* ; Cellular Senescence ; Disease Models, Animal ; Female ; Hepatitis B, Chronic/pathology* ; Hepatocytes/pathology* ; Humans ; In Situ Nick-End Labeling ; Liver/pathology* ; Liver Cirrhosis/pathology* ; Male ; Mice ; Mice, Transgenic ; Middle Aged ; Proliferating Cell Nuclear Antigen/analysis ; Trans-Activators/biosynthesis* ; Trans-Activators/genetics
Large liver cell dysplasia ; Hepatitis B virus ; HBX transgenic mouse ; Proliferation ; Apoptosis
OBJECTIVES: Large liver cell dysplasia (LCD) is frequently associated with hepatitis B virus (HBV), but it remains uncertain whether it is reactive, senescent or preneoplastic. METHODS: The HBX transgenic mice and normal control mice were sacrificed at 1, 3, 5, 7, 9, 11, 13 and 15 months after birth. Twenty-three cases of human B viral chronic hepatitis/cirrhosis with prominent LCD were selected. The immunohistochemical stain of proliferating cell nuclear antigen (PCNA), transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and senescence-associated beta-galactosidase (SA-beta-Gal) were evaluated. RESULTS: In HBX transgenic mice, LCD was developed since 3 months and formed small nodules of hepatocellular adenoma, which progressed to hepatocellular carcinoma. The hepatocytes with LCD in HBX transgenic mice showed significantly higher PCNA-labeling index (LI) and lower TUNEL-LI than normal hepatocytes of control mice (p < 0.05). In the majority of human B viral chronic hepatitis/cirrhosis, the hepatocytes with LCD revealed higher PCNA-LI and lower TUNEL-LI than those without, when compared in each case using the same tissue block. SA-beta-Gal staining showed no difference between hepatocytes with and without LCD. CONCLUSION: It is suggested that LCD, related to HBV, might not be just an innocent bystander, but closely related to hepatocarcinogenesis.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Koo, Ja Seung(구자승) ORCID logo https://orcid.org/0000-0003-4546-4709
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Park, Chan Il(박찬일)
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