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.

Serologic and genotypic characterization of hepatitis B virus in HIV-1 infected patients from South West and Littoral Regions of Cameroon

“…This is not surprising as inactive HBsAg carriers (diagnosed by absence of HBeAg and undetectable or low levels of HBV DNA) have been shown to form the largest group in chronic HBV infected patients [ 25 ]. It has also been shown that HBsAg levels are not always associated with serum HBV DNA levels since HBsAg synthesis can occur independent of HBV replication [ 26 ]. Several studies from the same region have reported HBV DNA amplifications of 47 % from HBsAg positive samples [ 22 , 27 ].…”

Quantitative intrahepatic HBV cccDNA correlates with histological liver inflammation in chronic hepatitis B virus infection

“…In addition, some previous studies have also demonstrated that the quantity of HBsAg in serum is correlated with the cccDNA copy number, which required a biopsy. 18,20 Furthermore, viral integration into the host genome has previously been reported to occur during the early stage of infection in chronic HBV infection. 21 Theoretically, a high preference for integration has been observed in DR1 and DR2 sequences of the HBV genome, and S gene sequences are often present in the integrated segments.…”

Review article: hepatitis B core‐related antigen (HBcrAg): an emerging marker for chronic hepatitis B virus infection

“…Serum HBsAg was shown to correlate moderately with intrahepatic cccDNA (r = .46, P <.001) (N = 82) . HBcrAg exhibited linear correlation with serum HBsAg titre (r = .703, P <.001) as well as the more sensitive assay of HBsAg, ie linearised HBsAg (HQ‐HBsAg) (r = .818, P <.001) (N = 404) …”