Serum HBV RNA predicts HBeAg clearance and seroconversion in patients with chronic hepatitis B treated with nucleos(t)ide analogues

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 log(10)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 log(10)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 log(10) 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.