The study was designed to investigate whether serum hepatitis B virus (HBV)
RNA is a strong
surrogate marker for intrahepatic HBV covalently closed
circular DNA (cccDNA) compared with serum HBV
DNA,
hepatitis B surface antigen (
HBsAg), and
hepatitis B e antigen (
HBeAg) in
HBeAg-positive
chronic hepatitis B (CHB) patients. Serum HBV
RNA, HBV
DNA,
HBsAg,
HBeAg, and intrahepatic cccDNA were quantitatively detected at baseline (n = 82) and 96 weeks (n = 62)
after treatment with nucleos(t)ide analogue (NUC) in
HBeAg-positive CHB patients. The correlations among serum HBV
RNA, HBV
DNA,
HBsAg,
HBeAg, and intrahepatic cccDNA levels were then statistically analyzed. The results showed that pretreatment intrahepatic cccDNA levels correlated better with serum HBV
DNA levels (r = 0.36, P < 0.01) than with serum HBV
RNA levels (r = 0.25, P = 0.02), whereas no correlations were found between pretreatment intrahepatic cccDNA levels and
HBsAg (r = 0.15, P = 0.17) or
HBeAg (r = 0.07, P = 0.56) levels. At 96 weeks after NUC treatment, intrahepatic cccDNA levels correlated well with
HBsAg levels (r = 0.39, P < 0.01) but not with serum HBV
RNA, HBV
DNA, and
HBeAg levels (all P > 0.05). Besides, the decline in the intrahepatic cccDNA level from baseline to week 96 correlated better with the reduction in the serum
HBsAg levels than with the decreases in the levels of the other markers (for the
HBsAg decline, r = 0.38, P < 0.01; for the HBV
DNA decline, r = 0.35, P = 0.01; for the HBV
RNA decline, r = 0.28, P < 0.05; for the
HBeAg decline, r = 0.18, P = 0.19). In conclusion, the baseline serum HBV
RNA level or its decline after 96 weeks of NUC
therapy correlated with the corresponding intrahepatic cccDNA level, while it was less than that seen with serum HBV
DNA at baseline and
HBsAg (or its decline) at 96 weeks
after treatment, respectively.