title: Serum hepatitis B surface antigen correlates with tissue covalently closed circular DNA in patients with hepatitis B-associated hepatocellular carcinoma.
abstract: Quantitation of hepatitis B surface antigen (HBsAg) in hepatitis B-associated hepatocellular carcinoma (HBV-HCC) remains to be clearly defined. This study aims to determine the association of HBsAg quantity with intrahepatic HBV viral load and activity in both tumor and non-neoplastic liver of HBV-HCC patients. Data were obtained from 89 prospectively enrolled patients treated with primary liver resection for HBV-HCC at a single Western institution (2008-2013). Circulating HBsAg was quantitated using ELISA. HBV DNA, covalently closed circular (cccDNA) and precore-pregenomic RNA (preC-pgRNA) in both tumor and non-neoplastic liver were quantitated by real-time PCR from fresh liver resection specimens. Circulating HBsAg was detectable in all 89 patients. HBsAg negatively correlated with age, and positively correlated with pre-operative serum AFP and ALT levels. HBsAg correlated with HBV cccDNA copy number in tumor or non-neoplastic liver tissue. It also correlated with preC-pgRNA copy number in non-neoplastic liver tissue. HBsAg did not correlate with serum HBV DNA, total intrahepatic HBV DNA, viral replicative activity or transcriptional activity. In HBV-HCC patients, HBsAg levels correlated with cccDNA copy number in tumor or non-neoplastic liver tissue, suggesting that a greater pool of cccDNA is associated with a higher rate of HBsAg production.
authors.affiliation: Department of Surgery, The Icahn School of Medicine at Mount Sinai, New York City, New York.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Surgery, The Icahn School of Medicine at Mount Sinai, New York City, New York.
authors.forename: Wei
authors.initials: W
authors.lastname: Luan
authors.affiliation: Department of Surgery, The Icahn School of Medicine at Mount Sinai, New York City, New York.
authors.forename: Leslie
authors.initials: L
authors.lastname: Warren
authors.affiliation: Department of Pathology, The Icahn School of Medicine at Mount Sinai, New York City, New York.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Fiel
authors.affiliation: Department of Surgery, The Icahn School of Medicine at Mount Sinai, New York City, New York.
authors.forename: Sima
authors.initials: S
authors.lastname: Blank
authors.affiliation: Department of Surgery, The Icahn School of Medicine at Mount Sinai, New York City, New York.
authors.forename: Hena
authors.initials: H
authors.lastname: Kadri
authors.affiliation: Department of Surgery, The Icahn School of Medicine at Mount Sinai, New York City, New York.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tuvin
authors.affiliation: Department of Surgery, The Icahn School of Medicine at Mount Sinai, New York City, New York.
authors.forename: Spiros P
authors.initials: SP
authors.lastname: Hiotis
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D004270:DNA, Circular / Q000235:genetics / Q000302:isolation & purification*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000821:virology; D006801:Humans; D008099:Liver / Q000821:virology; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D044967:Serum / Q000821:virology; D019562:Viral Load
chemical_list: D004270:DNA, Circular; D006514:Hepatitis B Surface Antigens
keywords: AFP; HBsAg; HCC; cccDNA