Background: This study was aimed at evaluating the clinical significance of serum HBV RNA, hepatitis B core-related antigen (HBcrAg) and hepatitis B core antibody (anti-HBc) levels in chronic hepatitis B patients with undetectable HBV DNA during nucleoside/nucleotide analogue (NA) treatment.
Methods: Fifty-seven patients who received long-term NA treatment of median 5.83 (25%, 75% percentiles 4.67, 7.75) years were enrolled, and 285 serum samples at five time points for each patient were quantitatively analysed for the three serum markers together with serum HBV DNA and hepatitis B surface antigen (HBsAg) levels.
Results: The HBV RNA level significantly correlated with HBcrAg (r=0.629; P<0.001) but not HBsAg levels (P=0.1460). Nonetheless, the HBcrAg level significantly correlated with the HBsAg level (r=0.469; P<0.001). Hepatitis B e antigen (HBeAg)-positive samples showed higher HBV RNA, HBcrAg and HBsAg levels than HBeAg-negative samples did (all P<0.05). Nine patients with HBeAg loss manifested a significantly greater decline in HBV RNA and HBcrAg levels (median 1.84 [25%, 75% percentiles 1.02, 2.12] log10 copies/ml, 1.14 [0.62, 2.21] log10 U/ml, respectively) compared with those in seven patients without HBeAg loss (0.74 [0.10, 1.08] log10 copies/ml and 0.41 [0.21, 0.69] log10 U/ml, respectively). Overall, serum HBV RNA, HBcrAg, HBsAg and anti-HBc levels gradually decreased with time during NA treatment. At the end of observation, HBV RNA and HBcrAg reached an undetectable level in 26 and 6 (46% and 11%) patients, respectively.
Conclusions: Monitoring of HBV RNA and HBcrAg levels is useful for NA-treated patients with undetectable HBV DNA. The attainment of HBV RNA undetectability usually occurs prior to HBcrAg undetectability.