title: Large liver cell dysplasia in hepatitis B virus x transgenic mouse liver and human chronic hepatitis B virus-infected liver.
abstract: 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.
authors.affiliation: Department of Pathology, Institute of Gastroenterology and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ja Seung
authors.initials: JS
authors.lastname: Koo
authors.forename: Je Kyung
authors.initials: JK
authors.lastname: Seong
authors.forename: Chanil
authors.initials: C
authors.lastname: Park
authors.forename: Dae-Yul
authors.initials: DY
authors.lastname: Yu
authors.forename: Bong-Kyeong
authors.initials: BK
authors.lastname: Oh
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Oh
authors.forename: Young Nyun
authors.initials: YN
authors.lastname: Park
mesh_terms: 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
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein