Molecular characterization of hepatitis B virus in the Democratic Republic of Congo: a systematic review

Abstract Background The Democratic Republic of the Congo (DRC) has a high burden of chronic hepatitis B (CHB), yet its hepatitis B virus (HBV) molecular epidemiology remains poorly characterized. This knowledge gap limits understanding of viral diversity and its implications for surveillance, diagnosis, treatment, and elimination efforts. We conducted the first preliminary nationwide synthesis of HBV molecular epidemiology in the DRC to characterize viral genetic diversity, recombinant forms, and clinically relevant mutations. Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we systematically searched publicly available databases for studies reporting HBV molecular characteristics from the DRC. Study quality was assessed using the Newcastle–Ottawa Scale (NOS). Data on HBV genotypes, subgenotypes, recombinant strains, antiviral resistance-associated mutations, and immune or vaccine escape mutations were extracted and quantitatively synthesized. Results Eight studies meeting the inclusion criteria and published up to April 2026 contributed a total of 273 HBV sequences collected between 2000 and 2023. Genotype E accounted for the largest proportion of reported sequences (53.8%), followed by genotype A (43.6%) and genotype D (2.2%). The distribution of HBV genotypes varied significantly across geographic regions of the DRC ( p < 0.001). Genotype A exhibited considerable genetic diversity, encompassing subgenotypes A1–A4, A8, quasi-A3, unclassified subgenotype A* variants and A/E recombinant strains, suggesting the circulation of multiple evolutionary lineages within the country. Antiviral resistance-associated substitutions were identified in 6.7% of the reported HBV sequences, while immune- and vaccine-escape substitutions were detected in 9.5% of isolates, indicating the presence of HBV variants with potential clinical and public health implications. Conclusions This systematic review reveals substantial HBV genetic diversity and marked geographic variation in the DRC, highlighting the limitations of national-level estimates and critical gaps in molecular surveillance. Strengthening nationwide genomic monitoring will be essential to inform targeted prevention, optimize treatment strategies, and support progress toward HBV elimination.