title: Preneoplastic markers of hepatitis B virus-associated hepatocellular carcinoma.
abstract: Hepatitis B virus (HBV) carriers are at high risk for the development of hepatocellular carcinoma (HCC), but there are no reliable markers that will identify such high-risk carriers. The objective of this work is to identify serologic markers that may indicate the early presence of HCC. Since HBV-encoded X antigen (HBxAg) likely contributes to HCC by up- or down-regulation of host gene expression, X positive and negative HepG2 cells were made and subjected to cDNA subtraction. When specific ELISAs were constructed measuring differentially expressed antigens and corresponding antibodies, antibodies to several differentially expressed genes were detected. In cross-sectional and longitudinal studies, antibodies were predominantly present in patients with HBV-associated cirrhosis and HCC, but not in most carriers with hepatic inflammation alone or without active liver disease. Antibodies were also present in patients with hepatitis C virus (HCV)-related HCC, but rarely detected in sera from uninfected individuals, those with tumors other than HCC, or those with drug-induced hepatitis. Statistical analysis showed that HCC patients with four or more antibodies detectable before the appearance of HCC had decreased survival, suggesting that these markers may reflect stepwise hepatocarcinogenesis. Hence, these antibodies may serve as preneoplastic markers for HCC in HBV carriers with chronic liver disease, and may be identified by a simple blood test.
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, Jefferson Medical College, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA.
authors.forename: Hie-Won L
authors.initials: HW
authors.lastname: Hann
authors.forename: Jungmin
authors.initials: J
authors.lastname: Lee
authors.forename: Anne
authors.initials: A
authors.lastname: Bussard
authors.forename: Catherine
authors.initials: C
authors.lastname: Liu
authors.forename: Yongri R
authors.initials: YR
authors.lastname: Jin
authors.forename: Koel
authors.initials: K
authors.lastname: Guha
authors.forename: Marcia M
authors.initials: MM
authors.lastname: Clayton
authors.forename: Kristin
authors.initials: K
authors.lastname: Ardlie
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pellini
authors.forename: Mark A
authors.initials: MA
authors.lastname: Feitelson
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000918:Antibody Specificity; D014408:Biomarkers, Tumor / Q000097:blood* / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000276:immunology / Q000821:virology*; D003430:Cross-Sectional Studies; D018076:DNA, Complementary / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000150:complications / Q000276:immunology; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000276:immunology / Q000821:virology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011230:Precancerous Conditions / Q000097:blood / Q000276:immunology / Q000821:virology*; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D006510:Hepatitis B Antibodies; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein