Predictive value of intrahepatic hepatitis B virus covalently closed circular DNA and total DNA in patients with acute hepatitis B and patients with chronic hepatitis B receiving anti-viral treatment

This study aimed to investigate the persistence and predictive values of intrahepatic (IH) hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and total DNA (tDNA) in patients with acute hepatitis B (AHB) and patients with chronic hepatitis B (CHB) receiving anti-viral treatment. The levels of IH cccDNA and tDNA, serum HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and alanine aminotransferase (ALT) were detected in 11 patients with AHB and 46 patients with CHB who were receiving anti-viral treatment, among whom 21 had primary treatment failure, 11 achieved virological response (VR) and 15 achieved VR and HBsAg seroclearance. The median IH cccDNA and tDNA levels in the patients with AHB (0.002 copies/cell and 0.04 copies/cell, respectively) were significantly lower than those in the patients with CHB. In the patients with CHB, the median IH cccDNA level among individuals who achieved VR and HBsAg seroclearance (0.012 copies/cell) was significantly lower than that in those who had failed primary treatment (4.18 copies/cell, P<0.0001) but not that in those who achieved solely VR (0.039 copies/cell, P=0.169). The median IH tDNA level in patients with CHB who achevied VR and HBsAg seroclearance (0.096 copies/cell) was significantly lower than that in those who failed primary treatment (371 copies/cell, P<0.0001) and those who achieved solely VR (1.62 copies/cell, P=0.001). No significant difference was observed in the area under the receiver operating characteristic (ROC) curve, which was used to predict the likelihood of achieving VR and HBsAg seroclearance, between IH tDNA and IH cccDNA levels (0.96 and 0.88, respectively; P>0.10). IH cccDNA levels were shown to be positively correlated with serum ALT (P=0.024), HBeAg (P=0.001) and IH tDNA levels (P<0.0001), but not with serum HBV DNA (P=0.12) and HBsAg levels in either HBeAg-positive (P=0.84) or in HBeAg-negative (P=0.146) patients. In conclusion, IH cccDNA may persist in patients with AHB and patients with CHB who acheive VR and HBsAg seroclearance following anti-viral treatment. Furthermore, IH cccDNA and tDNA may have potential in predicting successful therapeutic response in patients with CHB who receive anti-viral treatment.