Molecular Evaluation of Concomitant HBsAg, and Anti-HBs Positivity in Chronic Hepatitis B Patients


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Akdoğan Ö., Yapar D., SAYAN M., Savcı Ü., Kaplan G., Baykam N., ...More

Viral Hepatitis Journal, vol.32, no.1, pp.19-25, 2026 (ESCI, Scopus)

Abstract

Objectives: The hepatitis B virus (HBV) has a high mutation rate during replication, leading to the production of different variants. However, such atypical profiles could also be due to variant strains resulting from mutations. This study aimed to determine the mutations responsible for this profile and the presence of mutant strains by performing sequence analysis of the HBV pol/S gene regions in patients with chronic HB infection who were found to have coexisting HB surface antigen (HBsAg) and anti-HBs positivity during their follow-up. Materials and Methods: The study group consisted of patients who were found to be simultaneously positive for HBsAg and anti-HBs during routine follow-up for chronic HBV infection between 2021 and 2022. Mutations in the pol/S gene regions of HBV-DNA- positive patients were investigated using HBV-DNA sequencing technology. Results: The coexistence of HBsAg and anti-HBs was observed in 33 patients (3.8%). Anti-HBe was positive in all cases. Thirteen (39.4%) patients were HBV-DNA positive (minimum 6.9+E1 IU, maximum 3.7+E6 IU). All patients had HBV genotype D, and the D1/D2 ratio was 45.5%/54.6%. Among HBV-DNA-positive patients, 11 (84.6%) had pol/S gene mutations. Sixty-eight HBsAg mutations (42.8%) and 91 reverse transcriptase (RT) mutations (57%) were detected in these cases, representing a total of 159 mutations. In total, three patients (27.2%) had clinically significant HBsAg mutations, and four (36.3%) had RT mutations. Drug resistance was detected in 18.2% of cases. A vaccine-escape HBsAg mutation was detected in two cases (18.1%). Conclusion: The mutations detected in the pol/S gene sequence analyses of patients with HBsAg and anti-HBs coexistence seen in the course of chronic HB infection are naturally occurring, and the coexistence of HBsAg and anti-HBs could not be explained by these mutations.