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Intervirology. 2014;57(1):8-16. doi: 10.1159/000353851. Epub 2013 Aug 24.

Long-term efficacy of entecavir plus adefovir combination therapy versus entecavir monotherapy in adefovir refractory chronic hepatitis B patients with prior lamivudine resistance.

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Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital, Jeonju, South Korea.



We investigated the long-term efficacy of entecavir (ETV) + adefovir (ADV) combination therapy versus ETV monotherapy in lamivudine (LAM)-resistant chronic hepatitis B (CHB) patients who failed to respond to ADV rescue therapy.


A total of 91 ADV refractory patients with prior LAM resistance received ETV (1.0 mg/day) + ADV (10 mg/day) combination therapy (group A, n = 45) or ETV (1.0 mg/day) monotherapy (group B, n = 46) for more than 48 weeks.


The rates of undetectable serum hepatitis B virus DNA levels (≤20 IU/ml) at weeks 48 and 96 were not significantly different between group A and group B (31.1 vs. 23.9% at week 48, p = 0.442, and 44.7 vs. 34.5% at week 96, p = 0.457). However, the incidence of virological breakthrough in group A was significantly lower than that in group B (0 vs. 17.4% at week 48, p = 0.006, and 2.6 vs. 44.8% at week 96, p < 0.001). ETV monotherapy was the only independent factor significantly associated with virologic breakthrough (p = 0.015).


ETV + ADV combination therapy is a better therapeutic option than ETV monotherapy for ADV refractory CHB patients with prior LAM resistance.

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