Patterns of hepatitis b virus immune escape and pol/rt mutations across clinical cohorts of patients with genotypes a, e and occult hepatitis b infection in Nigeria: A multi-centre study

ABSTRACT

Hepatitis B virus (HBV) immune escape and Pol/RT mutations account for HBV immunoprophylactic, therapeutic, and diagnostic failure globally. Little is known about circulating HBV immune escape and Pol/RT mutants in Nigeria. This study focused on narrowing the knowledge gap of the pattern and prevalence of the HBV mutants across clinical cohorts of infected patients in southwestern Nigeria. Ninety-five enrollees were purposively recruited across clinical cohorts of HBV-infected patients with HBsAg or anti-HBc positive serological outcome and occult HBV infection. Total DNA was extracted from patients’ sera. HBV S and Pol gene-specific nested PCR amplification was carried out. The amplicons were further sequenced for serotypic, genotypic, phylogenetic, and mutational analysis. HBV S and Pol genes were amplified in 60 (63.2%) and 19 (20%) of HBV isolates, respectively. All the sixty HBV S gene and 14 of 19 Pol gene sequences were exploitable. The ayw4 serotype was predominant (95%) while ayw1 serotype was identified in 5% of isolates. Genotype E predominates in 95% of sequences, while genotype A, sub-genotype A3 was observed in 5%. Prevalence of HBV IEMs in the “a” determinant region was 29%. Commonest HBV IEM was S113T followed by G145A and D144E. The Pol/RT mutations rtV214A and rtI163V among others were identified in this study. This study provided data on the occurrence of existing and new HBV IEMs and Pol gene mutations in Nigeria.

KEYWORDS:

• HBV
• Immune escape mutation
• Pol mutations
• occult hepatitis B infection, clinical, Nigeria

Acknowledgements

The authors thank Dr Ijarotimi, Dr Abiola and the entire staff of the Gastroenterology unit of the Ladoke Akintola University Teaching Hospital, Osogbo, Nigeria for guidance and assistance in the course of the field in the unit. We also appreciate Dr Yusuf Musa and Dr Ariyo Olumuyiwa of the Federal Teaching Hospital, Ido-Ekiti, Dr Ijeoma Ifeorah for their kind gestures and support in the set-up of this study. We sincerely appreciate Mr Ekerette Udoh (E.U) for his support with data analysis. The authors would like to appreciate the African Centre of Excellence for Genomics of Infectious Diseases, Redeemers University, Ede for making laboratory facilities available to conduct this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Osasona G. Oluwadamilola (O.G.O) – conceptualisation, project management, sample collection, software, formal analysis, laboratory investigation, original draft preparation; Oguntoye Oluwatosin Oluwagbenga (O.O.O) – Manuscript review, editing, sample collection; Abdulkareem O.Lukman (A.O.L.) – manuscript review, editing, sample collection; Arowosaye Abiola Opeyemi (A.A.O.) – Sample collection, manuscript review, editting; Adewumi Moses Olubusuyi (A.M.O.)- Manuscript review and editing; Christian Happi (C.H.)- Conceptualisation, manuscript review and editing; Folarin Onikepe (F.O.) – Supervision, conceptualisation,manuscript review and editing.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21505594.2023.2218076.

Data Availability statement

The hepatitis B virus Polymerase and S gene sequences obtained from this study had been deposited in the Genbank sequence database under accession numbers OP420514 to OP420522, OP428653 to OP428701 https://mail.google.com/mail/u/0/#search/gb-admin%40ncbi.nlm.nih.gov/FMfcgzGqQSSScVjrPsPRrPvRSnpZmLjr.

Additional information

Funding

This research project was funded by the African Centre of Excellence for Genomics of Infectious Diseases, Redeemers University, Ede, Osun State.