Pretreatment and on-treatment indicators of virologic breakthrough of lamivudine therapy in chronic hepatitis B patients: An Egyptian study

Abstract

The primary objectives of hepatitis B treatment include improved clinical and histological progression as well as virus eradication. For many years, lamivudine was a first-line therapy for treating hepatitis B virus (HBV) infection. However, its long-term use is associated with high resistance rates (up to 70% after 5 years) due to mutations in the viral YMDD motif. The purpose of this study was to outline factors responsible for the development of viral resistance during long-term lamivudine therapy. Initially, 230 patients receiving lamivudine therapy for chronic hepatitis B (CHB) infection were enrolled in the study. All subjects received follow-ups in the first year to assess viral and biochemical responses. Only 136 and 104 patients received follow-up assessments during the second and third years of treatment, respectively. Viral breakthrough (VBT) occurred in 49 of 230 patients (21.3%). Hepatitis B "e" antigen (HBeAg) status before treatment was significantly associated with VBT in the first 2 years of treatment; however, this effect was not significant in the third year. Pre-treatment HBV DNA levels were predictive of VBT in the HBeAg-positive subgroup after all years of treatment (P = 0.001, P = 0.002, and P = 0.002, respectively). These levels were also predictive in the HBeAg-negative subgroup after 1 year of treatment (P = 0.001). In resource-poor communities, financial concerns drive the selection of antiviral therapy to treat CHB. Lamivudine monotherapy is a relatively cheap and effective treatment to manage CHB. However, consistent follow-ups and treatment modifications appear essential to prevent long-term treatment failure.