Long-Term Efficacy of Entecavir Plus Adefovir Combination Therapy versus Entecavir Monotherapy in Adefovir Refractory Chronic Hepatitis B Patients with Prior Lamivudine Resistance

Objectives: 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. Methods: 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. Results: 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). Conclusions: ETV + ADV combination therapy is a better therapeutic option than ETV monotherapy for ADV refractory CHB patients with prior LAM resistance.