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Summary: Background: Serum hepatitis B virus (HBV) RNA is a novel biomarker for evaluating treatment response. Detailed information regarding serum HBV RNA kinetics during treatment with nucleos(t)ide analogues (NAs) is limited. Aims: To ascertain serum HBV RNA kinetics during long‐term NA treatment and identify associated factors. Methods: We enrolled 76 HBeAg‐positive chronic hepatitis B patients receiving NA from randomised controlled trials. Laboratory assays were undertaken every 3 months. Factors associated with serum HBV RNA kinetics were identified by generalised estimating equations. Results: Baseline serum HBV RNA was 8.5 ± 1.0 log10 copies/mL. Decline in serum HBV RNA during NA therapy was biphasic: the first phase (HBV DNA detectable) had a fast decrease (median slope, −0.207 log10 copies/mL/month) and was followed by a second phase (HBV DNA undetectable) with slow decrease (median slope, −0.071 log10 copies/mL/month). In the first phase, factors independently associated with lower initial serum HBV RNA were male sex (OR, 0.685, P = 0.044), low baseline HBsAg (OR, 0.525, P = 0.001) and rapid virological response (RVR) (OR, 0.624, P = 0.031). In the second phase, only RVR was independently associated with serum HBV RNA kinetics, including its lower initial level (OR, 0.694, P = 0.043) and greater decline (OR, 0.966, P = 0.002). Based on viral dynamics, time needed to achieve undetectable serum HBV RNA from baseline was 43.56 (IQR: 29.49‐66.40) months. Conclusion: RVR was a significant determinant for biphasic decline in serum HBV RNA during NA treatment, which significantly influenced the treatment duration required to achieve undetectable serum HBV RNA. [ABSTRACT FROM AUTHOR]

Whether different serum HBV RNA detection assays can consistently predict treatment outcomes in patients with chronic hepatitis B remains controversial. We enrolled 188 patients who had stopped nucleos(t)ide analogues (NAs) (STOP cohort-1, -2) and 78 receiving entecavir (ETV) therapy (ETV cohort) and used double-target (targeting both 5′ and 3' ends of the HBV pregenome RNA [DT-RNA]) and three single-target (targeting the S-region [S-RNA], X-region [X-RNA], and poly-A tail of HBV RNA [PolyA-RNA]) assays to predict treatment outcomes. In STOP cohorts, DT-RNA, S-RNA and X-RNA at NAs cessation showed higher predictive powers for clinical relapse (time-dependent areas under the curve [AUCs] for years 1, 2, 3, and 4 ranged between 0.724 and 0.772 in cohort-1, and between 0.741 and 0.824 in cohort-2) than the PolyA-RNA (AUCs between 0.604 and 0.611 in cohort-1; and between 0.530 and 0.584 in cohort-2). The predictive power for 2-year HBeAg loss of the four targeted RNAs in the ETV cohort at 6 months were similar (AUCs, 0.848, 0.838, 0.825, and 0.801), and superior to that of the HBV DNA level at 6 months (AUC, 0.721). The outcome prediction performance of serum HBV RNAs is methodology-dependent. PolyA-RNA detection was not recommended to predict off-treatment relapses. • We developed various assays to quantify serum HBV RNA levels, referred to as DT-RNA, SRNA, X-RNA and PolyA-RNA. • HBV RNA levels detected by four assays are all capable for predicting HBeAg loss in ETV treated patients. • Three kinds of HBV RNA levels except PolyA-RNA are eligible for predicting off-treatment clinical relapse in CHB patients. [ABSTRACT FROM AUTHOR]