Comparison of lamivudine plus adefovir therapy versus entecavir with or without adefovir therapy for adefovir-resistant chronic hepatitis B

Background and Goals: Data regarding the management of adefovir (ADV) resistance are still limited. The aim of this study is to investigate treatment outcomes of rescue therapy in ADV-resistant chronic hepatitis B (CHB) patients.

Study: CHB patients who began rescue therapy due to documented genotypic resistance mutations to ADV between October 2006 and July 2012 were retrospectively reviewed.

Results: Sixty-three patients were included in this study. Most patients had history of lamivudine (LAM) resistance. Treatment response was evaluated at 3-month intervals up to 12 months. The cumulative rate of complete virologic response (CVR) in hepatitis B virus (HBV)-infected patients (HBV DNA<60 IU/mL) was 15.9%, 27.2%, 28.9%, and 31.7% after 3, 6, 9, and 12 months of rescue therapy. Thirty-five patients were treated with a combination of LAM plus ADV (LAM+ADV group) and 28 patients were treated with entecavir (ETV)-based therapy (ETV with or without ADV therapy, ETV±ADV group). The cumulative CVR rate was significantly higher in the ETV±ADV group than in the LAM+ADV group at month 12 (46.4% vs. 20.6%, respectively, P=0.040). Multivariate analysis showed that pretreatment serum HBV DNA levels at <6log10 IU/mL (hazard ratio: 34.109, P=0.001) and type of rescue therapy (hazard ratio: 4.944, P=0.036) were associated with CVR.

Conclusions: Lower baseline HBV DNA level and ETV±ADV therapy were the important predictive factors for CVR in ADVresistant CHB patients. This study suggests the need of early switching to a rescue therapy such as ETV±ADV at the time of low-level viremia.