Efficacy of 2 years of entecavir plus adefovir therapy in patients with chronic hepatitis B who had failed on prior nucleos(t)ide analog treatment

• Options are limited for chronic hepatitis B patients who have previously failed on multiple nucleos(t)ide analogs.
• 2 years’ rescue therapy with entecavir (ETV) + adefovir (ADV) proved effective and well tolerated in such patients.
• The HBV DNA level just prior to initiation of ETV + ADV can predict the efficacy of 2 years of ETV + ADV treatment.
• Similarly, the magnitude of the HBV DNA reduction at 1 year can also predict the efficacy of 2 years of ETV + ADV treatment.

Entecavir (ETV) plus adefovir (ADV) combination therapy may be a promising option for chronic hepatitis B (CHB) patients who have failed on prior nucleos(t)ide analog (NA) treatment. However, the long-term efficacy and safety of this combination are not well-defined. In a single-center, retrospective study, 104 patients (mean age 31.7 years; 88.5% male) with HBV DNA >103 IU/mL who had received one or multiple prior NAs for ⩾6 months (median 44.5 months) were treated for ⩾24 months with ETV (0.5 mg/day) plus ADV (10 mg/day). Among patients with available samples, 44/90 (48.9%) had drug-resistant mutations. At 2 years, HBV DNA levels were undetectable (<12 IU/mL) in 52/104 (50.0%) patients. The mean HBV DNA level was 2.0 ± 1.2 log 10 IU/mL, and it was decreased by 3.2 ± 2.0 log 10 IU/mL from the pre-combination treatment (V0) value. The 2-year HBeAg loss rate was 14.4% (13/90), HBeAg seroconversion rate was 10.0% (9/90), and ALT normalization rate was 75%. In multivariate analyses, the prior NA treatment duration, the V0 HBV DNA level, and the HBV DNA reduction at 1 year after ETV + ADV therapy were associated with the virological response after 2 years. No patients developed renal impairment, clinical decompensation or new HCC, and no relapses of HCC or deaths occurred. Thus, 2-year rescue therapy with ETV + ADV was effective and well-tolerated in CHB patients who had previously failed on multiple NA treatments. The HBV DNA level just before ETV + ADV combination therapy and the decrease of HBV DNA at 1 year could predict the efficacy of 2 years of ETV + ADV treatment.