OVERLAPPING POL/S GENE ANALYSIS IN CHRONIC HEPATITIS B PATIENTS WITH COEXISTING HBSAG AND ANTI-HBs

Introduction: Simultaneous HBsAg and anti-HBs positivity can be seen in patients with chronic hepatitis B (CHB) infection. The paradoxical phenomenon of ongoing viral replication despite the presence of neutralizing antibodies makes simultaneous HBsAg and anti-HBs positivity one of the most interesting atypical serological profiles. The aim of this study was to investigate the relationship between the coexistence of HBsAg and anti-HBs and S gene mutations in study and control groups with CHB infection. Materials and methods: Patients included in the study group were HBsAg and anti-HBs positive; patients in the control group were HBsAg positive and anti-HBs negative. The hepatitis B virus pol gene (reverse transcriptase region, amino acids 80-250) was sequenced by the Sanger dideoxy method. HBV primary/compensatory nucleos(t)ide analog resistance mutations and pol/S gene overlap mutations were both analyzed. Results: Of the 2990 patients followed for CHB, 121 (4%) exhibited simultaneous HBsAg and HBs positivity. Serologic subtype was identified as homologous ayw2 in all patients in both groups. Amino acid changes in the "a" determinant were detected in 6 of the 21 patients in the study group but none were detected in the control group. HBsAg vaccine escape, HBIg escape, and diagnostic escape mutations were detected in 6 patients in the study group. In the control group, only 1 patient carried a vaccine escape mutation. Conclusions: The presence of HBsAg escape mutants observed in our study seem consistent with the variant HBsAg hypothesis. However, the absence of a typical HBsAg escape mutation in the MHR or "a" determinant in many of the patients in the study group suggests that this atypical profile may also arise via a different mechanism.