title: Core antigen expression is associated with hepatic necroinflammation in e antigen-negative chronic hepatitis B patients with low DNA loads.
abstract: Intrahepatic hepatitis B virus (HBV) core antigen (HBcAg) is a hallmark of viral replication in hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B (CHB). The aim of this study was to evaluate the role of HBcAg in HBeAg-negative CHB. One hundred six HBeAg-negative CHB patients who underwent ultrasonographically guided liver biopsy were reviewed for their HBV DNA load and clinical and histological data. Factors associated with the expression of intrahepatic HBcAg were analyzed. Among the patients, 35 (33%) were positive for HBcAg by immunohistostaining. In patients whose HBV DNA loads were higher than 10(7) copies (cp)/ml, nearly one-half (52%) had detectable HBcAg. Compared with HBcAg-negative patients, HBcAg-positive patients had higher serum alanine transaminase (ALT) and HBV DNA levels and more-severe hepatic necroinflammation. High serum ALT level (>160 U/liter) and HBV viral load were the determinants of HBcAg expression in multivariate analysis. Large amounts of HBcAg expression were frequently detected in patients with high DNA loads, and the patterns of HBcAg distribution were not related to histological activity or HBV DNA levels. In patients with lower HBV DNA loads, the expression of HBcAg was the key factor associated with active hepatic necroinflammation (hazard ratio = 11.25; 95% confidence interval [CI], 1.42 to 89.26; P = 0.022). In conclusion, the expression of HBcAg is not frequent in HBeAg-negative CHB. The expression of intrahepatic HBcAg indicates active hepatic necroinflammation, even in patients with low HBV DNA load. Both HBV viral load and HBcAg expression have implications in the pathogenesis of HBeAg-negative CHB.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, 201 Shih-Pai Road, Sec. 2, Taipei 112, Taiwan. yhhuang@vghtpe.gov.tw
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Huang
authors.forename: Hung-Hsu
authors.initials: HH
authors.lastname: Hung
authors.forename: Che-Chang
authors.initials: CC
authors.lastname: Chan
authors.forename: Chiung-Ru
authors.initials: CR
authors.lastname: Lai
authors.forename: Chi-Jen
authors.initials: CJ
authors.lastname: Chu
authors.forename: Teh-Ia
authors.initials: TI
authors.lastname: Huo
authors.forename: Pui-Ching
authors.initials: PC
authors.lastname: Lee
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Su
authors.forename: Keng-Hsin
authors.initials: KH
authors.lastname: Lan
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Huang
authors.forename: I-Cheng
authors.initials: IC
authors.lastname: Lee
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Lin
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000378:metabolism; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006512:Hepatitis B Core Antigens / Q000378:metabolism*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000473:pathology* / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D019562:Viral Load / Q000502:physiology; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase