Type II Ground Glass Hepatocytes Are Strongly Associated with Fibrosis Stage and Hepatocellular Carcinoma
Fang-Ying Kuo, Jacob Alexander, Michael Torbenson, Matthew Yeh. Chang Gung Medical Center, Kaohsiung, Taiwan; Univ of Washington, Seattle; Johns Hopkins Univ, Baltimore
Background: Ground glass hepatocytes (GGH) can be found in chronic hepatitis B (HBV) infection and contain surface antigens (HBs) in the endoplasmic reticulum. Two types of GGH have been described: an inclusion-like pattern in hepatocytes with a scattered distribution throughout the lobules (type I) and a peripheral staining of hepatocytes with distinct clustering of cells in the lobules (type II). Studies have shown type II GGH contain mutants with deletions over pre-S2 region in HBV genome and may represent preneoplastic lesions of HBV-related hepatocellular carcinoma (HCC). In fact, it has been shown small islands of clonal hepatocytes with integrated HBV can expand. The aim of this study is to investigate the distribution patterns of HBs in GGH on immunohistochemistry (IHC), and their association with the development of HCC.
Design: Explanted or resected livers from 45 HBV patients, including 20 non-HCC (9 cirrhotic and 11 non-cirrhotic) and 25 HCC (11 cirrhotic and 14 non-cirrhotic) were retrieved. Formalin fixed sections were immunostained for HBs. The patterns of HBs expression on IHC were examined and the clustering of the type II GGH in liver was semiquantitatively assessed: 1: 1-25%; 2: 26-49%; 3:50-74%; 4:>75%. Histology of the HCCs was examined. Ishak scores were obtained in the non-tumor livers.
Results: In the non-tumor livers, type I GGH was not associated with HCC and were present in 18/20 (90%) of cases without HCC and in 22/25 (88%) of cases with HCC(p=0.8). In contrast, type II GGH were present in 11/22 (50%) of cases without HCC and in 21/25 (84%) of cases with HCC (p=0.03). Further supporting a link with HCC, type II GGH predominated in cases with HCC: they outnumbered type I GGH in 30% of cases without HCC vs 95% of cases with HCC (p=0.0002). Further, type II GGH were in clusters in 9/20 (45%) non-HCC and 21/25 (84%) HCC cases (p=0.005). Also, livers harboring HCC had more extensive type II GGH clusters (p=0.01). Type II GGH in clusters were more common in advanced than in early fibrosis (stages 3-6 vs 0-2, p=0.04) but there was no difference when comparing low vs high Ishak inflammation grade (0-3 vs 4 and above, p=1). The presence of type II GGH did not show an association with any specific histologic type of HCC. Type II GGH was not associated with HBe Ag, anti-HBe, or HBV DNA levels.
Conclusions: While type I GGH do not appear to be associated with HCC, type II GGH are strongly associated with HCC: they are more frequent and have a distinctive clustering pattern in cases with HCC.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 252, Tuesday Morning