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Background/Aims: Adefovir (ADV) and lamivudine (LAM) combination therapy (ADV+LAM) has been a useful option forpatients with LAM-resistant (LAM-r) chronic hepatitis B (CHB). However, the long-term outcomes of LAM+ADV and 1-mgentecavir (ETV) rescue therapies have still been limited. The aim of this study was to determine the long-term outcomesof these two rescue therapies. Methods: Sixty patients with LAM-r CHB underwent rescue therapy with LAM+ADV (n=36) or 1-mg ETV (n=24). Wedetermined the duration of rescue therapy, timing and type of mutation, undetectable serum hepatitis B virus (HBV)DNA by PCR (lower limitation of detection, <140 copies/mL), biochemical response (alanine aminotransferase <40 IU/mL), and the incidence of hepatitis B virus e antigen (HBeAg) seroconversion and virologic breakthrough. Results: Baseline characteristics did not differ between the two therapy groups. The duration of rescue therapy was 56months (range, 14-100 months) in the ADV+LAM group and 42 months (range, 12-73 months) in the ETV group (P =0.036). The cumulative rates of HBV DNA undetectability and HBeAg seroconversion up to 6 years were 88.6% and 43.0%,respectively, in the ADV+LAM group, and 45.8% and 31.8% in the ETV group. The rate of virologic breakthrough andresistance was 14.4% in the ADV+LAM group and 71.9% in the ETV group (P =0.001). Conclusions: Combination of LAM and ADV therapy for up to 6 years achieved modest rates of virological suppressionand resistance. ETV is not an optimal therapy because the risk of viral breakthrough to ETV increases over time.

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