Abstract: Objective The purpose of this study was to investigate sequential or combined rescue antiviral therapy by tenofovir amibufenamide (TMF) in entecavir(ETV)-treated chronic hepatitis B (CHB) patients with low-level viremia(LLV). Methods Eighty-nine patients with CHB who had ETV treatment for at least 24 months were encountered in our hospital between January 2021 and December 2023, and high-sensitive PCR detection found complete virological response (CVR) in 52 cases and LLV in 37 cases. For rescue antiviral therapy, ETV and TMF combination was given in 14 patients, switching to TMF in 12 patients and continuation on ETV in 11 patients for 48 weeks. Multivariate Logistic regression analysis was applied to find risk factors for LLV occurrence. Results Baseline serum ALT and AST levels in patients with LLV were (36.0±5.2)yr, (54.2±7.0)U/L and (43.5±7.4)U/L, all much younger or lower than [(38.9±5.8)yr, (143.0±6.8)U/L and (85.4±7.1)U/L, respectively, P<0.05], while serum HBV DNA load, HBeAg positive rate, HBsAg level and liver stiffness measurement (LSM) were (7.2±2.6)lg IU/ml, 82.7%, 6300.8(5123.9, 8912.4)IU/ml and (8.6±1.0)kPa, all much higher than [(5.4±1.4)lg IU/ml, 40.5%, 3002.0(2413.4, 4512.4)IU/ml and (7.1±0.7)kPa, respectively, P<0.05] in those with CVR; multivariate Logistic regression analysis showed that high serum HBV DNA loads, serum HBeAg positive and high serum HBsAg levels were all the independent risk factors for occurrence of LLV (P<0.05) in CHB patients receiving ETV antiviral treatment; by end of 48 week rescue therapy, serum HBV DNA transferred to negative, serum ALT and LSM were (35.1±4.7)U/L and (6.9±0.6)kPa in patients with ETV and TMF combination treatment, much superior to in other two groups (P<0.05). Conclusion LLV could occur in CHB patients receiving ETV antiviral therapy, and combination of ETV and TMF is an efficacious choice for rescue therapy, which needs long-term clinical observation.

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