This study evaluated the predictive value of serum HBV
DNA, HBV
RNA, HBcrAg,
HBsAg, intrahepatic HBV
DNA and cccDNA for
HBeAg clearance and seroconversion during long-term treatment with nucleos(t)ide analogues (
NAs) in patients with
chronic hepatitis B (CHB). A single centre, prospective cohort of CHB patients was used for this study. Serum HBV
RNA levels were retrospectively measured at baseline, 6, 12, 24, 36, 48, 60, 72 and 84 months post-
NAs treatment. Serum
HBsAg and HBcrAg levels were quantified at baseline, month 6, 60 and 72. Histological samples from liver biopsy at baseline and month 60 were analysed for intrahepatic HBV
DNA and cccDNA. Eighty-three
HBeAg-positive patients were enrolled with a median follow-up time of 108 months (range 18-138 months). Of them, 53 (63.86%) patients achieved
HBeAg clearance, and 37 (44.58%) achieved
HBeAg seroconversion. Cox multivariate analysis showed that only baseline HBV
RNA was independently associated with
HBeAg clearance and seroconversion (<5.45 log10 copies/mL, HR = 5.06, 95% CI: 1.87-13.71, p = .001; HR = 3.38, 95% CI: 1.28-8.91, p = .01). The independent association with
HBeAg clearance and seroconversion remained for HBV
RNA levels at month 6 (<4.72 log10 copies/mL, HR = 4.16, 95% CI: 1.61-10.72, p = .003; HR = 6.52, 95% CI: 1.85-22.94, p = .003) and month 12 (<4.08 log10 copies/mL, HR = 3.68, 95% CI: 1.96-6.90, p < .001; HR = 2.79, 95% CI: 1.31-5.94, p = .008). The AUCs of baseline HBV
RNA for predicting the
HBeAg clearance (0.83, 95% CI: 0.70-0.96, 0.83, 95% CI: 0.70-0.96 and 0.82, 95% CI: 0.69-0.95 respectively) and seroconversion (0.89, 95% CI: 0.77-1.00; 0.81, 95% CI: 0.66-0.95 and 0.84, 95% CI: 0.71-0.98 respectively) at month 36, 60 and 84 were higher than those of HBV
DNA,
HBsAg and HBcrAg. In conclusion, lower serum HBV
RNA at baseline, month 6 and 12 post-
NAs treatment could predict
HBeAg clearance and seroconversion during long-term
NAs treatment.