Abstract: Objective The aim of this study was to investigate the risk factors of low-level viremia (LLV) and rescue switch treatment to tenofovir alafenamide fumarate (TAF) in entecavir(ETV)-treated patients with chronic hepatitis B(CHB). Methods A total of 158 patients with CHB were enrolled in our hospital between January 2020 and December 2022, and all were already had treated with ETV for at least 48 weeks. The patients who obtained complete virological response (CVR) continued the ETV treatment, and those with LLV were switched to TAF treatment. The patients in the two groups were observed for 48 weeks. Serum HBV DNA loads were detected by hypersensitive PCR detection system, serum HBeAg and HBsAg quantification were detected by full-automatic chemiluminescence immunoanalyzer. The risk factors of LLV in CHB patients undergoing ETV treatment were analyzed by multivariate Logistic regression analysis. Results Out of the 158 patients with CHB enrolled in this study, the LLV was found in 55 cases(34.8%)and the CVR in 103 cases (65.2%); the body mass index, family hepatitis B history, concomitant liver cirrhosis, baseline serum HBV DNA loads, serum HBeAg positive and serum HBsAg levels were correlated to the occurrence of LLV(P＜0.05), and the multivariate Logistic regression analysis showed that the baseline serum HBV DNA loads (OR:2.793, 95%CI:1.579-4.940), serum HBeAg positive (OR:2.337,95%CI:1.455-3.756) and serum HBsAg high levels (OR:1.931, 95%CI:1.338-2.786) were the independent risk factors for LLV occurrence in ETV-treated patients with CHB (P＜0.05); at the end of 48-week of TAF treatment, the CVR was obtained in 36 cases (65.5%) in 55 patients with LLV, and serum ALT level, HBV DNA load and HBsAg level in 55 patients with LLV were still significantly higher than those with CVR [37.2(19.1,57.0)U/L, (0.9±0.4)lg IU/ml and (3.9±0.6)lg IU/ml vs. 33.5(17.6, 39.2)U/L, (0.7±0.3)lg IU/ml and (3.1±0.5)lg IU/ml, respectively, P＜0.05]. Conclusion The high baseline serum HBV DNA loads, HBeAg positive and high HBsAg quantification might be the risk factors for LLV occurrence in ETV-treated patients with CHB and the rescue TAF treatment could get CVR in most of them, which warrants further clinical investigation.

Key words: Hepatitis B, Low-level viremia, Entecavir, Tenofovir alafenamide fumarate, Risk factor, Rescue treatment