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

Abstract

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 31.7years; 88.5% male) with HBV DNA >103IU/mL who had received one or multiple prior NAs for ⩾6months (median 44.5months) were treated for ⩾24months with ETV (0.5mg/day) plus ADV (10mg/day). Among patients with available samples, 44/90 (48.9%) had drug-resistant mutations. At 2years, HBV DNA levels were undetectable (<12IU/mL) in 52/104 (50.0%) patients. The mean HBV DNA level was 2.0±1.2log10IU/mL, and it was decreased by 3.2±2.0log10IU/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 1year after ETV+ADV therapy were associated with the virological response after 2years. 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 1year could predict the efficacy of 2years of ETV+ADV treatment.