Abstract: Objectiv To explore the efficacy and safety of tenofovir disoproxil fumarate（TDF） and entecavir （ETV） in the treatment of chronic hepatitis B （CHB） patients with viral DNA polymerase 204 site mutation infection. Methods 87 CHB patients with HBV polymerase 204 site mutation infection due to resistance to lamivudine or adefovir therapy were recruited in this study between August of 2013 and September 2015,and 44 patients received TDF and 43 received ETV treatment. The peripheral CD4⁺T lymphocyte counts were detected by FCM,and creatinine clearance （Crcl） was calculated based on serum creatinine levels. Results At the end of 24 w,48 w and 72 w treatment,serum HBV DNA loss in TDF-treated patients were 63.6%,79.6% and 95.5%,significantly higher than 35.6%,55.6% and 82.2%,respectively,in ETV-treated patients（P<0.05）,and serum ALT normalization rates were 84.1%,90.9% and 93.2%,while they were 65.1%（P<0.05）,83.7% and 90.7% in ETV-treated patients;the peripheral blood CD4⁺T cell counts were （481.5±232.4）/μl,（536.5±297.5）/μl and （566.5±321.6）/μl,no significantly different as compared to （475.3±229.3）/μl,（565.8±255.9）/μl and （565.1± 256.5）/μl in ETV-treated patients （P<0.05）;the Crcl levels were （101.2±40.1） ml/min,（104.3±26.8） ml/min and （98.7±21.5） ml/min,also without significantly different as compared to （105.2±42.6） ml/min,（102.5±30.6） ml/min and （99.6±26.8） ml/min in ETV-treated patients（P<0.05）. Conclusion TDF might be the priority option in dealing with CHB patients with HBV mutant infection for rescue therapy as it works early,convenient and safe.

Key words: Hepatitis B, Tenofovir disoproxil fumarate, Entecavir, Rescue therapy, LAM-resistant, ADV-resistant