Abstract: Objective This study was conducted to investigate clinical efficacy of tenofovir disoproxil fumarate (TDF) and entecavir (ETV) in rescue therapy of patients with lamivudine-resistant HBeAg-negative chronic hepatitis B (CHB). Methods Fifty patients with lamivudine-resistant HBeAg-negative CHB were enrolled in our hospital between January 2017 and December 2021, and we randomly assigned them to receive TDF (n=25) or ETV for rescue antiviral therapy for 48 weeks. Multivariate Logistic regression analysis was applied to predict impacting factors for virological response. Results by 4, 12, 24, 36 and 48 weeks of antiviral treatment, serum HBV DNA loss in TDF-treated patients were 32%, 60%, 72%, 80% and 92%, all much higher than 4%, 24%, 32%, 40% and 44% (all P<0.05) in ETV-treated patients; serum ALT normalization rates in TDF-treated patients were 56%, 68%, 80%, 84% and 96%, all much higher than 16%, 32%, 52%, 56% and 72% (P<0.05) in ETV-treated patients; by end of 48 week treatment, serum creatinine level in TDF-treated patients increased greatly as compared to that at presentation (85.4±13.9μmol/L vs. 76.2±17.5μmol/L, P=0.0001), while it didn’t change obviously in ETV-treated patients (76.6±12.9μmol/L vs. 77.3±11.2μmol/L, P=0.769); multivariate Logistic regression analysis showed that administration of TDF and serum HBV DNA loads were independent factors impacting virologcal response to rescue therapy. Conclusion Based on our findings, we recommend TDF rescue antiviral therapy for CHB patients with lamivudine-resistant, and surveillance of renal functions might be important during the antiviral procedure.

Key words: Hepatitis B, Lamivudine-resistance, Tenofovir, Entecavir, Rescue therapy