Large liver cell dysplasia in hepatitis B virus x transgenic mouse liver and human chronic hepatitis B virus-infected liver.
OBJECTIVE
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.


CONCLUSIONS
It is suggested that LCD, related to HBV, might not be just an innocent bystander, but closely related to hepatocarcinogenesis.
Koo
Ja Seung
JS
Department of Pathology, Institute of Gastroenterology and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Seong
Je Kyung
JK
Park
Chanil
C
Yu
Dae-Yul
DY
Oh
Bong-Kyeong
BK
Oh
Seung Hyun
SH
Park
Young Nyun
YN
D000328:Adult; D000818:Animals; D017209:Apoptosis; D016922:Cellular Senescence; D004195:Disease Models, Animal; D005260:Female; D019694:Hepatitis B, Chronic / Q000473:pathology*; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins
D018809:Proliferating Cell Nuclear Antigen; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein