Serum hepatitis B surface antigen correlates with tissue covalently closed circular DNA in patients with hepatitis B-associated hepatocellular carcinoma

J Med Virol. 2016 Feb;88(2):244-51. doi: 10.1002/jmv.24326. Epub 2015 Jul 21.

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.

Keywords: AFP; HBsAg; HCC; cccDNA.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / virology*
  • DNA, Circular / genetics
  • DNA, Circular / isolation & purification*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / isolation & purification*
  • Hepatitis B, Chronic / complications*
  • Hepatitis B, Chronic / virology
  • Humans
  • Liver / virology
  • Liver Neoplasms / virology*
  • Male
  • Middle Aged
  • Prospective Studies
  • Real-Time Polymerase Chain Reaction
  • Serum / virology
  • Viral Load

Substances

  • DNA, Circular
  • Hepatitis B Surface Antigens