Background & Aims: Correlations between serum
viral markers and intrahepatic cccDNA in patients undergoing long-term nucleos(t)ide analogues (
NAs) treatment haven't been fully explored. In this study, we evaluate the correlation between intrahepatic cccDNA and other serum
viral markers and intrahepatic HBV
DNA in
HBeAg positive
chronic hepatitis B (CHB) patients during 60-month treatment with
NAs. Methods: Fifty-four
HBeAg positive CHB patients received long-term
NAs treatment were included in this study. Serial serum samples were regularly collected and quantitatively analyzed for
HBsAg, HBV
DNA, HBV
RNA and HBcrAg. Histological samples from liver biopsy at baseline and month 60 were analyzed for intrahepatic HBV
DNA and cccDNA. Results: At baseline, serum HBV
DNA plus
RNA was positively associated with intrahepatic cccDNA in multivariate regression analysis (β=0.205, P<0.001). In the correlation analysis between cccDNA and serum
viral markers, HBV
DNA plus
RNA had the highest correlation coefficient (r=0.698, P<0.001), followed by serum HBV
DNA (r=0.641, P<0.001), HBV
RNA (r=0.590, P<0.001), and HBcrAg (r=0.564, P<0.001). At month 60, correlations between these serum
viral markers and cccDNA were not observed (P>0.05). Multivariate regression analysis showed that only the decreased HBV
DNA plus
RNA was positively associated with cccDNA decline (β=0.172, P =0.006). Changes of HBV
DNA plus
RNA (r=0.525, P=0.001) was better correlated with cccDNA decline as compared to HBV
RNA (r=0.384, P=0.008), HBV
DNA (r=0.431, P=0.003), and
HBsAg (r=0.342, P=0.029). Conclusions: Serum HBV
DNA plus
RNA better correlated with intrahepatic cccDNA than other viral makers before and during
NAs treatment in
HBeAg positive CHB patients.