HBV RNA at 6 months after nucleos(t)ide analogues treatment can predict antiviral efficacy in chronic hepatitis B patients

BACKGROUND: This multicenter study evaluated serum HBV RNA as a prognostic biomarker for nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB), focusing on correlations with HBV DNA/HBsAg and predictive value for virological response (VR) and HBeAg seroconversion. METHODS: From 2020 to 2024, 427 treatment-naive HBeAg-positive CHB patients across nine Chinese hospitals were enrolled. Longitudinal HBV RNA-DNA-HBsAg correlations were analyzed during 24-month NA therapy. Predictive performance for VR at 12 months and HBeAg seroconversion at 24 months was assessed. RESULTS: copies/mL, P = 0.001). Pretreatment HBV RNA correlated with HBV DNA (r = 0.638, P = 0.001), shifting to HBsAg post-24-month treatment (r = 0.917, P = 0.0005). HBV DNA and RNA levels at 6 months independently predicted therapeutic outcomes. For VR, HBV DNA demonstrated a hazard ratio (HR) of 0.16 (P < 0.001) with an area under the ROC curve (AUROC) of 0.889, while HBV RNA showed an HR of 0.77 (P = 0.03) and AUROC of 0.754. For HBeAg seroconversion, HBV DNA yielded an HR of 0.01 (P = 0.015) with AUROC 0.900, and HBV RNA exhibited an HR of 0.72 (P = 0.03) and AUROC 0.703, underscoring their consistent prognostic value at this critical timepoint. CONCLUSIONS: HBV RNA dynamics transition from DNA- to HBsAg-associated correlations during NA therapy. Early declines in HBV DNA/RNA at 6 months predict VR and HBeAg seroconversion, establishing this time as a a robust and clinically practical early prediction point. HBV RNA complements existing biomarkers for optimizing CHB management.