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Background & Aims: The clinical value of quantitative hepatitis B surface antigen (qHBsAg) titer in patients taking nucleot(s)ide analogs(NAs) is still controversial.This study aims to investigate the dynamic changes of qHBsAg titers and its significance for predicting virological response(VR) and serological response(SR) to long-term entecavir (ETV) treatment.Methods : Forty-eight ETV-naǐve patients were enrolled and followed prospectively for 4 years, and 32 of them were HBeAg-positive at baseline.Serum alanine aminotransferase(ALT), qualitative hepatitis B virus(HBV) serological markers, and HBV DNA were detected; and qHBsAg titers were measured using Elecsys(@) HBsAg Ⅱ Quant Assay.Results: The mean baseline HBV-DNA and qHBsAg were 7.51 log copies/mL and 3.78 log IU/mL, respectively.After 48 months of ETV treatment, the rates of VR(<291 copies/mL), ALT normalization and SR(HBeAg/anti-HBe) were 89.6%(43/48), 89.6%(43/48) and 34.4%(11/32), respectively.There was a decline in qHBsAg titers from baseline to months 48, ranging from 3.78 to 3.10 log IU/mL.The greatest decline of HBsAg was observed in the first 3 months of treatment (0.47 logl0 IU/mL), which was significantly correlated with corresponding HBV-DNA decreasing (3.89 log copies/mL) (P=0.032).By using ROC analysis, qHBsAg titers at baseline (AUC=0.647) and 3 months after treatment (AUC=0.586) had poor power in predicting of 48-month VR; qHBsAg titers at baseline (AUC=0.779) and 3 months after ETV treatment (AUC=0.658) had poor power in predicting of 48-month SR in HBeAg-positive patients at baseline.Additionally, the declines of qHBsAg in the first 3 months of treatment also had poor power in predicting of either 48-month VR or SR.Conclusions: ETV is efficacious in NAs-naǐve patients, and qHBsAg titers declined significantly in the first 3 months of ETV treatment.However, qHBsAg titer is not a good predictor of 4-year virological and HBeAg/anti-HBe serological responses in this cohort.