Prolonged Entecavir Therapy Is Not Effective for HBeAg Seroconversion in Treatment-Naive Chronic Hepatitis B Patients with a Partial Virological Response

The aims of this study were to investigate the efficacy of prolonged entecavir (ETV) therapy in treatment-naive chronic hepatitis B (CHB) patients and to determine whether continuous ETV therapy is feasible to achieve HBeAg seroconversion, particularly in patients with partial virological response (PVR). A total of 142 treatment-naive patients with CHB were enrolled. The mean duration of treatment was 65 (range, 26 to 90) months, and 86 patients (60.6%) were HBeAg positive. PVR was defined as detectable hepatitis B virus (HBV) DNA (>116 copies/ml) at year 1. The cumulative incidence of virological response (VR) increased from 54.9% at year 1 to 98.2% at year 7. HBeAg positivity (odds ratio [OR], 4.146; P = 0.001) and initial alanine aminotransferase (ALT) (OR, 0.997; P = 0.004) were independent risk factors for PVR. Among the 64 patients with PVR, 47 patients (73.4%) achieved VR within 4 years after prolonged ETV therapy without treatment adaptation. Three patients (2.1%) experienced virological breakthrough and HBV variants with genotypic resistance. The cumulative rate of HBeAg seroconversion was significantly higher in the patients with VR than in the patients with PVR (P = 0.018). None of the PVR patients with HBV DNA at ≥5,000 copies/ml at year 1 ever experienced HBeAg seroconversion. Multivariate analysis identified VR at year 1 as the only determinant of HBeAg seroconversion (hazard ratio [HR], 3.009; P = 0.010). In conclusion, although there were patients with PVR, prolonged ETV therapy showed excellent VR, with only 2.1% emergence of viral resistance during a 7-year follow-up. However, to achieve HBeAg seroconversion, drug modification is needed for HBeAg-positive patients with PVR (especially those with HBV DNA at ≥5,000 copies/ml at year 1).