Three Years of Continuous Entecavir Therapy in Treatment-naïve Chronic Hepatitis B Patients: VIRAL Suppression, Viral Resistance, and Clinical Safety

Objectives: We aimed to determine the antiviral potency, viral resistance rate, and clinical safety of 3-year continuous entecavir treatment.

Methods: We determined the cumulative rates of undetectable hepatitis B virus DNA (HBV DNA) levels (< 12 IU/ml), hepatitis B e antigen (HBeAg) seroconversion, alanine aminotransferase (ALT) normalization, and entecavir signature mutations (using the sensitive line probe assay) and monitored any side effects for 222 treatment-naïve chronic hepatitis B (CHB) patients (40.5% HBeAg positive) on continuous entecavir treatment for 3 years.

Results: The median age and follow-up duration were 45 years and 25.1 months, respectively. In all, 222, 188, and 101 patients had been followed up for at least 1, 2, and 3 years, respectively. There were incremental increases in the rates of HBV DNA undetectability, HBeAg seroconversion, and ALT normalization reaching to 92.1, 43.9, and 90.4% at year 3, respectively. In all, 100 and 76.5% of patients with baseline HBV DNA levels < and ≥ 8 logs copies/ml, respectively, had undetectable HBV DNA at year 3. The cumulative rate of entecavir-resistant mutations was 1.2% at year 3. Three patients experienced virologic breakthrough, one with resistance development, one with subsequent HBeAg seroconversion, and one with subsequent decline in HBV DNA. Two patients with baseline rt204I mutations responded to entecavir treatment. There were no serious adverse events.

Conclusions: Using very sensitive HBV DNA and viral resistance assays, continuous entecavir treatment for treatment-naïve CHB patients for 3 years was associated with >90% chance of undetectable HBV DNA and only 1.2% chance of emergence of entecavir-resistant mutations.