Abstract: Objective This study was conducted to observe clinical efficacy of rescue antiviral therapy of tenofovir alafenamide (TMF) in entecavir(ETV)-treated chronic hepatitis B (CHB) patients with low level viremia (LLV). Methods 85 patients with CHB were encountered in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between September 2021 and February 2023, all enrolled patients had been treated by ETV for at least 48 weeks, and LLV was found by quantitatively PCR detection. The patients were divided into group A, B and C, receiving ETV (n=28),TMF (n=26) or ETV and TMF combination (n=31) for 48 weeks. Serum HBsAg level was detected by chemiluminescent immunoassays and serum HBV DNA loads were determined by real-time fluorescent quantitative PCR. Fibrosis factor-4 (FIB-4) and estimated glomerular filtration rate (eGFR) were routinely obtained. Liver stiffness measurement (LSM) was detected by FibroScan. Results By end of 48 week antiviral treatment, serum HBV DNA load in group C was(12.3±3.4)IU/mL, much lower than [(31.3±5.8)IU/mL, P＜0.05] in group B or [(244.1±14.1)IU/mL, P＜0.05] in group A, while there were no significant differences respect to serum HBsAg levels among the three groups [(4322.6±210.2)IU/mL vs.(4323.1±150.2)IU/mL or vs.(4453.5±143.3)IU/mL, P>0.05]; there were no significant differences as respect to serum bilirubin, AST and ALT levels among the three groups (P>0.05); LSM in group C was (6.6±0.5)kPa, and in group B was (6.4±0.8)kPa, both significantly lower than [(7.6±1.2)kPa, P＜0.05] in group A, while FIB-4 and eGFR were not significantly different among the three groups (P>0.05). Conclusion For CHB patients with LLV after ETV treatment, we recommend TMF rescue therapy, while combination of nucleos(t)ide analogue needs further clinical investigation.

Key words: Hepatitis B, Tenofovir alafenamide, Entecavir, Low level viremia, Rescue therapy