Correlation between intrahepatic hepatitis B virus cccDNA levels and other activity markers in patients with HBeAg-negative chronic hepatitis B infection

Abstract

The aim of this study was to demonstrate the relation between intrahepatic (IH) hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) levels and the other HBV replicative intermediates and hepatocyte expression of HBV antigens. Patients with hepatitis B surface antigen (HBsAg) positivity, hepatitis B early antigen negativity, serum HBV DNA levels 10 copies/ml or more, and constantly or intermittently increased alanine aminotransferase levels were included. Fifty-nine patients were included. There was a good correlation between the levels of IH HBV cccDNA and serum HBV DNA (P<0.001). Serum HBsAg levels were weakly correlated with IH HBV cccDNA levels and moderately correlated with serum HBV DNA (r=0.322, P=0.017; r=0.489, P=0.001, respectively). There were no significant correlation between serum HBsAg level and histologic activity index groups (P=0.691), but stage 0, 1, and greater than 2 fibrosis groups were positively correlated with serum HBsAg levels (P=0.019). IH cccDNA and serum HBV DNA were significantly different in hepatitis B core antigen staining groups (P=0.008 and <0.001, respectively) but there was no significant correlation between HBsAg staining groups and HBV replication markers. There was a weak correlation between serum HBsAg levels and IH HBsAg and hepatitis B core antigen levels (r=0.333, P=0.012; r=0.366, P=0.006, respectively). In multivariate analysis, alanine aminotransferase, age, fibrosis stage, and serum HBsAg quantitation were the most important factors predicting IH HBV cccDNA level. Histopathologic damage, serum HBV DNA levels, and IH HBV replication markers have a more complex and dynamic process. However, both serum and IH HBV replication markers provide important knowledge about the activity of the disease.