title: Type II ground-glass hepatocytes as a marker of hepatocellular carcinoma in chronic hepatitis B.
abstract: Ground-glass hepatocytes are seen in chronic hepatitis B virus (HBV) infection and are known to harbor pre-S mutants, which are implicated in the pathogenesis of hepatocellular carcinoma (HCC). However, the association between ground-glass hepatocytes and HCC has yet to be clearly elucidated. The aim in the present study was to investigate the association of ground-glass hepatocytes with (1) the histologic characteristics of HBV-related HCC and (2) the grade of inflammation, stage of fibrosis, serologic markers of HBV infection, HBV viral load, and α-fetoprotein levels. We evaluated 45 hepatectomy specimens from chronic HBV-infected patients: 25 with HCC and 20 without. In comparison with those without HCC, cases with HCC had a significantly higher prevalence of type II ground-glass hepatocytes (84% versus 55%, P = .0488), demonstrating a geographically clustered pattern (84% versus 45%, P = .0102) and exceeding type I in the individual samples (84% versus 35%, P = .0005). Type II ground-glass hepatocytes also had a statistically significant association with higher stages of fibrosis, being present in 21 cases (66%) with Ishak fibrosis stages 3 to 6 as compared with only 4 cases (31%) without type II ground-glass hepatocytes (P = .0176). In conclusion, type II ground-glass hepatocytes are more likely to be present in cases of HCC, growing in a clustered pattern, and are also associated with advanced fibrosis in chronic HBV infection. Our data suggest that a growth advantage or clonal proliferation of hepatocytes with mutant hepatitis B surface antigen may play a role in the pathogenesis of HBV-related HCC with clinical relevance.
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors.forename: Alka Mary
authors.initials: AM
authors.lastname: Mathai
authors.forename: Jacob
authors.initials: J
authors.lastname: Alexander
authors.forename: Fang-Ying
authors.initials: FY
authors.lastname: Kuo
authors.forename: Michael
authors.initials: M
authors.lastname: Torbenson
authors.forename: Paul E
authors.initials: PE
authors.lastname: Swanson
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Yeh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000821:virology; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000235:genetics; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000150:complications / Q000473:pathology* / Q000821:virology; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D019562:Viral Load; D055815:Young Adult
chemical_list: D006514:Hepatitis B Surface Antigens
keywords: Ground-glass hepatocytes; HCC; Hepatitis B surface antigen; Hepatitis B virus infection; Hepatocellular carcinoma; Histopathology; hepatocellular carcinoma