Abstract
Approximately 50% of hepatocellular carcinoma (HCC) is attributable to chronic infection with hepatitis B virus (HBV). Serum hepatitis B surface antigen (HBsAg) is an important diagnostic marker of HBV infection, whereas intrahepatic HBV covalently closed circular DNA (cccDNA) is a surrogate marker of HBV persistence. This study aimed to investigate relationships between serum HBsAg, intrahepatic HBsAg, and intrahepatic cccDNA in HBV-associated HCC. Intrahepatic HBsAg was determined by immunohistochemistry in matched non-cancerous and HCC tissues from 88 patients; 56 patients (63.64%) were serum HBsAg positive. In serum HBsAg-positive group, intrahepatic HBsAg was positive staining in 73.2% of non-cancerous tissues, but only in 10.7% of HCC tissues. Significant correlation between serum HBsAg and intrahepatic HBsAg was observed in non-cancerous tissues (p < 0.001), but not in HCC tissues (p = 0.415). Absolute quantification of intrahepatic cccDNA was performed by droplet digital PCR in tissues from 30 patients; 18 patients (60%) were serum HBsAg positive. In serum HBsAg-positive group, intrahepatic cccDNA was detected in 66.66% of non-cancerous tissues, but only in 5.55% of HCC tissue; intrahepatic cccDNA levels in non-cancerous tissues were significantly higher than those in HCC tissues (p < 0.001), and correlated with serum HBsAg (p < 0.01). Significant correlations between intrahepatic HBsAg and intrahepatic cccDNA were found in both non-cancerous tissues (p < 0.01) and HCC tissues (p < 0.05). We concluded that HBV cccDNA and intrahepatic HBsAg in HBV-associated HCC tissues were significantly reduced, as compared with matched non-cancerous tissues. This warrants further investigation into the impacts and the cause(s) of cccDNA reduction in HBV-associated HCC tissues, which might yield novel immune-related therapy for HBV-associated HCC.