Original Research

Molecular detection of hepatitis B virus genotype E with immune escape mutations in chronic hepatitis B patients on long-term antiviral therapy in Jos, Nigeria

Joseph Anejo-Okopi, Edith Okeke, Pantong M. Davwar, Chika Onwuamah, Harris Onywera, Patience Omaiye, Mary Duguru, Ocheme J. Okojokwu, Otobo I. Ujah, Bulus Jonathan, Chima A. George, Ramyil S. Crown, Fiyaktu B. Yakubu, Judith O. Sokei, Leona C. Okoli, Onyemocho Audu, Seth C. Inzaule, Isaac O. Abah, Patricia Agaba, Oche O. Agbaji, Atiene S. Sagay, Claudia Hawkins
African Journal of Laboratory Medicine | Vol 11, No 1 | a1677 | DOI: https://doi.org/10.4102/ajlm.v11i1.1677 | © 2022 Joseph Anejo-Okopi, Edith Okeke, Pantong M. Davwar, Chika Onwuamah, Harris Onywera, Patience Omaiye, Mary Duguru, Ocheme J. Okojokwu, Otobo I. Ujah, Bulus Jonathan, Chima A. George, Ramyil S. Crown, Fiyaktu B. Yakubu, Judith O. Sokei, Leona C. Okoli, Onye | This work is licensed under CC Attribution 4.0
Submitted: 19 July 2021 | Published: 18 October 2022

About the author(s)

Joseph Anejo-Okopi, Department of Microbiology, University of Jos, Jos, Nigeria; and, AIDS Prevention Initiative in Nigeria, Jos University Teaching Hospital, Jos, Nigeria
Edith Okeke, Department of Internal Medicine, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
Pantong M. Davwar, Department of Internal Medicine, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
Chika Onwuamah, Center for Human Virology and Genomics Nigeria Institute of Medical Research, Lagos, Nigeria
Harris Onywera, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; and, Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town, South Africa; and, Research, Innovations, and Academics Unit, Tunacare Services Health Providers Limited, Nairobi, Kenya
Patience Omaiye, Department of Internal Medicine, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
Mary Duguru, Department of Internal Medicine, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
Ocheme J. Okojokwu, Department of Microbiology, University of Jos, Jos, Nigeria
Otobo I. Ujah, Department of Community and Family Health, College of Public Health, University of South Florida, Tampa, Florida, United States
Bulus Jonathan, Department of Family Medicine, Plateau State Specialist Hospital, Jos, Nigeria
Chima A. George, Department of Family Medicine, Bingham University Teaching Hospital, Jos, Nigeria
Ramyil S. Crown, Department of Medical Microbiology and Parasitology, Bingham University Teaching Hospital, Jos, Nigeria
Fiyaktu B. Yakubu, Department of Chemical Pathology, Jos University Teaching Hospital, Jos, Nigeria
Judith O. Sokei, Center for Human Virology and Genomics Nigeria Institute of Medical Research, Lagos, Nigeria
Leona C. Okoli, Center for Human Virology and Genomics Nigeria Institute of Medical Research, Lagos, Nigeria
Onyemocho Audu, Department of Epidemiology and Community Health, Benue State University, Makurdi, Nigeria
Seth C. Inzaule, Department of HIV and Global Hepatitis Program, World Health Organization, Geneva, Switzerland
Isaac O. Abah, Department of Pharmacology, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
Patricia Agaba, AIDS Prevention Initiative in Nigeria, Jos University Teaching Hospital, Jos, Nigeria; and, Department of Family Medicine, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
Oche O. Agbaji, Department of Internal Medicine, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
Atiene S. Sagay, Department of Obstetrics and Gynaecology, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
Claudia Hawkins, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States


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Abstract

Background: Previous studies in Nigeria have reported the presence of hepatitis B virus (HBV) genotype E and the availability of immune escape mutants. There is a paucity of data on chronic patients on long-term antiviral therapy for HBV infection.

Objective: This study assessed HBV genotypes and drug resistance variants among patients with chronic HBV infection receiving tenofovir in Jos, Nigeria.

Methods: This cross-sectional study consecutively enrolled 101 patients (51 with HIV/HBV co-infection and 50 with HBV infection only) on antiviral therapy from February 2018 to May 2019 at four hospitals in Jos, Nigeria. DNA quantification of HBV was performed on all samples; 30 samples with detectable viral load were selected for genotyping using Sanger sequencing by targeting the full-length sequences of reverse transcriptase gene of the HBV genome. Phylogenetic analysis was performed with reference sequences from GenBank. Escape mutant and drug resistance analysis were performed using HBV drug resistance interpretation and Geno2pheno.

Results: Only 30 (29.7%) of the 101 study participants had detectable HBV DNA. Of these, six (20.0%) isolates were successfully amplified and sequenced. The identified genotype was E, including escape mutations L127R (16.7%) and G145A (16.7%).

Conclusion: This study revealed exclusive dominance of genotype E in Nigeria. The S gene mutations G145A and L271R are known to be associated with modified antigenicity and impaired serologic assays, which may cause false negatives in the detection of anti-HBV surface antigen. The presence of mutants that are associated with vaccine immune escape may also have diagnostic and vaccine immune response implications.

 


Keywords

hepatitis B virus (HBV); genotyping; antiviral drug resistance; chronic hepatitis B

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