Abstract: Objective The aim of this study was to investigate influencing factors of low level viremia (LLV) in patients with chronic hepatitis B (CHB) during nucleos(t)ide analogues (NAs) antiviral treatment. Methods A retrospective study was conducted on 212 patients with CHB between May 2022 and May 2024, and all enrolled patients had received regular NAs treatment for more than 48 weeks in our hospital. Serum HBeAg and HBV DNA loads were routinely detected. AST/platelet count ratio index (APRI) and based on four fibrosis factors (FIB-4) score were calculated. LLV was defined as serum HBV DNA loads were at range of 20 to 2000 IU/ml. Peripheral blood T cells, B cells, NK lymphocyte subsets were determined by FCA. Liver stiffness measurement (LSM) was detected by Fibrotouch. Multivariate Logistic regression analysis was applied to reveal impacting factors for LLV occurrence. Results Of 212 patients with CHB in our series, prevalence of LLV was 33.5%, with complete virological response (CVR) of 66.5%; mean age at baseline in patients with LLV was (42.4±10.2)yr, much younger than [(46.4±12.0)yr, P＜0.05] in patients with CVR, percentages of hepatitis B family history, concomitant fatty liver, entevavir(ETV) antiviral treatment, high loads of serum HBV DNA, serum HBeAg positive and low serum AST level in patients with LLV were 80.3%, 53.5%, 63.4%, 83.1%, 93.0% and 66.2%, all significantly higher than 41.1%, 42.6%, 48.9%, 36.2%, 44.0% and 34.8%, respectively (all P＜0.05) in patients with CVR; FIB-4 score and LSM in patients with LLV were 1.21(0.87, 1.78) and 7.2(6.4, 8.1)kPa, both significantly greater than [1.76(1.23, 2.44) and 6.5(5.9, 7.1)kPa, respectively, P＜0.05] in those with CVR; multivariate Logistic regression analysis showed that hepatitis B family history (OR=0.181, P=0.002), serum HBeAg positive (OR=3.892, P＜0.001) and low serum AST level (OR=0.269, P==0.001) were all the independent risk factors impacting occurrence of LLV; there were no significant differences as respect to percentages of peripheral blood CD4⁺ and CDO8⁺ cells as well as CD4⁺/CD8⁺ cell ratio between patients with LLV and those with CVR [(35.9±6.9)%, (30.8±8.6)% and (1.3±0.5) vs. (36.0±7.7)%, (29.1±8.1)% and (1.4±0.6), respectively, P >0.05]. Conclusion Serum HBeAg positive, low serum ALT level and high serum HBV DNA loads, and family history of hepatitis B at baseline are the impacting factors of LLV during antiviral treatment by NAs in patients with CHB, which warrants further clinical investigation as early intervention might improve prognosis.

Key words: Hepatitis B, Nucleos(t)ide analogues, Low level viremia, Impacting factors, Therapy