A336C/A336T/T337C variations in HBV core gene and spontaneous hepatitis B e antigen loss in chronic hepatitis B patients

BACKGROUND: A336C/A336T/T337C variations in HBV core gene were demonstrated to relate to the decreases in serum HBV DNA levels and HBV replication in chronic hepatitis B patients. Usually the drastic decrease in serum HBV DNA levels correlates with spontaneous HBeAg loss during the course of chronic HBV infection. The aim of the present study was to investigate whether there was correlation between A336C/A336T/T337C variations and spontaneous HBeAg loss METHODOLOGY/PRINCIPAL FINDINGS: A modified PCR-RFLP assay and ELISA were adopted to determine A336C/A336T/T337C variations and serum HBeAg levels in chronic hepatitis B patients without any antiviral therapy, respectively, whereas G1896A variation and HBV genotype were detected using Taqman-PCR assay. RFLP pattern C, E, G, C/G mixture and a new pattern C' were found in this study. A336C/A336T/T337C variations occurred in 40/166(24.1%) chronic hepatitis B patients. Chi-square test showed that C336/T336/C337 variants was more frequent in chronic hepatitis B patients with A1896 variants than those with the wild type G1896 (χ2 = 4.7, P = 0.03), and moreover, patients with C336/T336/C337 variants had a significantly lower HBeAg-positive percentage than those with the wild type A336/T337. Binary logistic regression identified genotype B (OR = 4.1, 95%CI = 1.8-9.2, P = 0.001), the presence of C336/T336/C337 variants (OR = 3.2, 95%CI = 1.2-8.5, P = 0.02) and A1896 variants (OR = 7.8, 95%CI = 3.3-18.5, P < 0.001) as independent factors associated with spontaneous HBeAg loss. CONCLUSION/SIGNIFICANCE: A336C/A336T/T337C were naturally occurring polymorphisms in HBV core gene, and moreover, the presence of C336/T336/C337 variants was first demonstrated to be an independent factor associating with spontaneous HBeAg loss in chronic hepatitis B patients.