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For: Kew MC, Kramvis A, Yu MC, Arakawa K, Hodkinson J. Increased hepatocarcinogenic potential of hepatitis B virus genotype A in Bantu-speaking sub-saharan Africans. J Med Virol 2005;75:513-21. [PMID: 15714494 DOI: 10.1002/jmv.20311] [Citation(s) in RCA: 115] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]

For:	Kew MC, Kramvis A, Yu MC, Arakawa K, Hodkinson J. Increased hepatocarcinogenic potential of hepatitis B virus genotype A in Bantu-speaking sub-saharan Africans. J Med Virol 2005;75:513-21. [PMID: 15714494 DOI: 10.1002/jmv.20311] [Citation(s) in RCA: 115] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]

Number

Cited by Other Article(s)

Maponga TG, McNaughton AL, Campbell C, de Cesare M, Mokaya J, Lumley SF, Bonsall D, Ip CL, Chai H, Van Rensburg C, Glashoff RH, Waddilove E, Preiser W, Blackard JT, Ansari MA, Kramvis A, Andersson MI, Matthews PC. A putative hepatitis B virus sequence motif associated with hepatocellular carcinoma in South African adults. Ann Hepatol 2025;30:101763. [PMID: 39986372 DOI: 10.1016/j.aohep.2024.101763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 09/27/2024] [Accepted: 11/14/2024] [Indexed: 02/24/2025]

Affiliation(s)

Tongai G Maponga Division of Medical Virology, Stellenbosch University, Faculty of Medicine and Health Sciences, Tygerberg, Cape Town, South Africa; National Health Laboratory Service, Tygerberg Business Unit, Tygerberg, Cape Town, South Africa
Anna L McNaughton Nuffield Department of Medicine, University of Oxford, Oxford, UK
Cori Campbell Nuffield Department of Medicine, University of Oxford, Oxford, UK
Mariateresa de Cesare Nuffield Department of Medicine, University of Oxford, Oxford, UK
Jolynne Mokaya Parasites and Microbes, Wellcome Sanger Institute, Hinxton, UK
Sheila F Lumley Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
David Bonsall Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK; Big Data Institute, Old Road, Oxford OX3 7FZ, UK
Camilla Lc Ip Nuffield Department of Medicine, University of Oxford, Oxford, UK
Haiting Chai Nuffield Department of Medicine, University of Oxford, Oxford, UK
Christo Van Rensburg Division of Gastroenterology, Stellenbosch University, Faculty of Medicine and Health Sciences, Tygerberg, Cape Town, South Africa
Richard H Glashoff National Health Laboratory Service, Tygerberg Business Unit, Tygerberg, Cape Town, South Africa; Immunology Unit, Division of Medical Microbiology, Stellenbosch University, Faculty of Medicine and Health Sciences, Tygerberg, Cape Town, South Africa
Elizabeth Waddilove The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
Wolfgang Preiser Division of Medical Virology, Stellenbosch University, Faculty of Medicine and Health Sciences, Tygerberg, Cape Town, South Africa; National Health Laboratory Service, Tygerberg Business Unit, Tygerberg, Cape Town, South Africa
Jason T Blackard University of Cincinnati College of Medicine, Cincinnati, OH, USA
M Azim Ansari Nuffield Department of Medicine, University of Oxford, Oxford, UK
Anna Kramvis Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, University of the Witwatersrand, 7 York Road, Parktown, 2193 Johannesburg, South Africa
Monique I Andersson Division of Medical Virology, Stellenbosch University, Faculty of Medicine and Health Sciences, Tygerberg, Cape Town, South Africa; Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
Philippa C Matthews The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Division of Infection and Immunity, University College London, Gower Street, London WC1E 6BT, UK; Department of Infectious Diseases, University College London Hospital, Euston Road, London NW1 2BU, UK.

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Maquessene O, Laurindo O, Chambal L, Ismael N, Mabunda N. Serological and Molecular Characterization of the Hepatitis B Virus in Blood Donors in Maputo City, Mozambique. Viruses 2025;17:94. [PMID: 39861883 PMCID: PMC11768953 DOI: 10.3390/v17010094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 01/06/2025] [Accepted: 01/09/2025] [Indexed: 01/27/2025] Open

Zhang M, Mouzannar K, Zhang Z, Teraoka Y, Piotrowski J, Ishida Y, Tateno-Mukaidani C, Saito T, Abe-Chayama H, Chayama K, Liang TJ. Hepatitis B virus genotypes A1 and A2 have distinct replication phenotypes due to polymorphisms in the HBx gene. PLoS Pathog 2025;21:e1012803. [PMID: 39787208 PMCID: PMC11717313 DOI: 10.1371/journal.ppat.1012803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 12/03/2024] [Indexed: 01/12/2025] Open

Abstract

HBV genotype A has two major subtypes, A1 (commonly in Africa) and A2 (commonly in Europe) with only 4% nucleotide differences. Individuals infected with these two subtypes appear to have different clinical manifestations and virologic features. Whether such a difference results from the virus or host has not been established. Using HBV generated from molecule clones of subtypes A1 and A2 in cell culture (HBVcc), we demonstrate that HBVcc of subtypes A1 and A2 can be passaged in vitro and in vivo and respond equally well to human IFN-α treatment. HBVcc passaged in human liver chimeric mice (HBVmp) infected human hepatocytes more efficiently than that of the original HBVcc. Subtype A2 showed a much higher viral replication level than that of subtype A1. Mechanistic investigations using constructs with chimeric A1/A2 sequences and specific mutations indicated that subtype A2 has an inherently higher replication phenotype due to specific polymorphisms in the HBx gene resulting in amino acid variations. Studies of HBx expression demonstrated that A1 HBx is expressed at a much lower level than that of A2 HBx. Mutagenesis studies identified two HBx amino acid variations responsible for the observed phenotypic difference. Using AlphaFold2, we generated structural models of HBx proteins of A1 and A2. Superposition of the two models reveal that the overall structural motifs are similarly aligned, except for the C-terminal peptides diverging between the A1 and A2 models, possibly explaining their functional difference. In conclusion, using various in vitro and in vivo models, here we show that subtype A2 has an inherently higher replication phenotype due to polymorphisms in HBx that result in possible differences in structure and expression level of the two subtype HBx proteins. This genotypic difference potentially explains the reported clinical differences between the two subtypes as well as providing a previously unrecognized association between viral sequence variations and clinical manifestations of HBV infection in humans.

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Mthethwa L, Parboosing R, Msomi N. MicroRNA levels in patients with chronic hepatitis B virus and HIV coinfection in a high-prevalence setting; KwaZulu-Natal, South Africa. BMC Infect Dis 2024;24:833. [PMID: 39148016 PMCID: PMC11328411 DOI: 10.1186/s12879-024-09715-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Accepted: 08/02/2024] [Indexed: 08/17/2024] Open

Abstract

BACKGROUND

Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection are significant public health issues, despite the availability of an effective HBV vaccine for nearly three decades and the great progress that has been made in preventing and treating HIV. HBV and HIV both modulate micro-ribonucleic acids (microRNA) expression to support viral replication. The aim of this study was to describe the pattern of microRNA expression in patients coinfected with chronic HBV and HIV with varying disease severity, as indicated by Hepatitis B e antigen (HBeAg) status, HBV viral load, alanine transaminase (ALT) levels, and HIV viral load.

METHODS

Plasma microRNAs, specific to HBV, were measured by quantitative real-time polymerase chain reaction (qRT-PCR) in HBV and HIV-negative healthy controls (n = 23) and patients coinfected with chronic HBV-HIV (n = 50). MicroRNA expression levels were compared between patients with high vs low HBV viral load, HBeAg positive vs HBeAg negative, high vs low ALT levels, and high vs low HIV viral load. Additionally, HBV viral load, ALT levels, and HIV viral load were correlated with microRNA expression levels.

RESULTS

Significantly higher expression levels of selected microRNAs were observed in chronic HBV-HIV coinfected patients compared to healthy controls. Significantly higher expression levels of hsa-miR-122-5p, hsa-miR-192-5p, and hsa-miR-193b-3p were observed in patients with high HBV viral load compared with low HBV viral load patients, and the levels of these microRNAs were correlated with HBV viral load levels. Significantly higher levels of hsa-miR-15b-5p and hsa-miR-181b-5p were observed in HBeAg-negative patients.

CONCLUSION

This study demonstrates the potential use of hsa-miR-15b-5p, hsa-miR-122-5p, hsa-miR-181b-5p, hsa-miR-192-5p and hsa-miR-193b-3p as additional diagnostic biomarkers in chronic HBV disease progression.

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Padarath K, Deroubaix A, Naicker P, Stoychev S, Kramvis A. Comparison of the Proteome of Huh7 Cells Transfected with Hepatitis B Virus Subgenotype A1, with or without G1862T. Curr Issues Mol Biol 2024;46:7032-7047. [PMID: 39057060 PMCID: PMC11275860 DOI: 10.3390/cimb46070419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 07/01/2024] [Accepted: 07/03/2024] [Indexed: 07/28/2024] Open

Phinius BB, Anderson M, Gobe I, Mokomane M, Choga WT, Phakedi B, Ratsoma T, Mpebe G, Makhema J, Shapiro R, Lockman S, Musonda R, Moyo S, Gaseitsiwe S. High Prevalence of Hepatitis B Virus Drug Resistance Mutations to Lamivudine among People with HIV/HBV Coinfection in Rural and Peri-Urban Communities in Botswana. Viruses 2024;16:592. [PMID: 38675933 PMCID: PMC11054684 DOI: 10.3390/v16040592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 04/07/2024] [Accepted: 04/09/2024] [Indexed: 04/28/2024] Open

Affiliation(s)

Bonolo B. Phinius Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (B.B.P.); (M.A.); (G.M.); (J.M.); (R.S.); (S.L.); (R.M.); (S.M.) School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Private Bag UB 0022, Gaborone, Botswana; (I.G.); (M.M.)
Motswedi Anderson Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (B.B.P.); (M.A.); (G.M.); (J.M.); (R.S.); (S.L.); (R.M.); (S.M.)
Irene Gobe School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Private Bag UB 0022, Gaborone, Botswana; (I.G.); (M.M.)
Margaret Mokomane School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Private Bag UB 0022, Gaborone, Botswana; (I.G.); (M.M.)
Wonderful T. Choga Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (B.B.P.); (M.A.); (G.M.); (J.M.); (R.S.); (S.L.); (R.M.); (S.M.) School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Private Bag UB 0022, Gaborone, Botswana; (I.G.); (M.M.)
Basetsana Phakedi Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (B.B.P.); (M.A.); (G.M.); (J.M.); (R.S.); (S.L.); (R.M.); (S.M.)
Tsholofelo Ratsoma Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (B.B.P.); (M.A.); (G.M.); (J.M.); (R.S.); (S.L.); (R.M.); (S.M.)
Gorata Mpebe Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (B.B.P.); (M.A.); (G.M.); (J.M.); (R.S.); (S.L.); (R.M.); (S.M.)
Joseph Makhema Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (B.B.P.); (M.A.); (G.M.); (J.M.); (R.S.); (S.L.); (R.M.); (S.M.) Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
Roger Shapiro Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (B.B.P.); (M.A.); (G.M.); (J.M.); (R.S.); (S.L.); (R.M.); (S.M.) Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
Shahin Lockman Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (B.B.P.); (M.A.); (G.M.); (J.M.); (R.S.); (S.L.); (R.M.); (S.M.) Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
Rosemary Musonda Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (B.B.P.); (M.A.); (G.M.); (J.M.); (R.S.); (S.L.); (R.M.); (S.M.)
Sikhulile Moyo Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (B.B.P.); (M.A.); (G.M.); (J.M.); (R.S.); (S.L.); (R.M.); (S.M.) School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Private Bag UB 0022, Gaborone, Botswana; (I.G.); (M.M.) Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, Private Bag X1, Matieland 7602, South Africa School of Health Systems and Public Health, University of Pretoria, Private Bag X20, Pretoria 0028, South Africa
Simani Gaseitsiwe Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (B.B.P.); (M.A.); (G.M.); (J.M.); (R.S.); (S.L.); (R.M.); (S.M.) Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA

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Hepatitis B virus preCore/Core region variability in pregnant women in the Republic of Guinea. JOURNAL OF MICROBIOLOGY, EPIDEMIOLOGY AND IMMUNOBIOLOGY 2024;101:61-71. [DOI: 10.36233/0372-9311-447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]

Abstract Introduction. The vertical route of hepatitis B virus (HBV) transmission is a significant problem in African countries, which is characterized by late diagnosis of the disease and high mortality. The high prevalence of hepatocellular carcinoma (HCC) in Africa may be due to variability in the HBV preCore/Core region, mutations in which contribute to disease progression. Molecular genetic characterization of strains circulating among pregnant women may reflect the overall mutational profile of the pathogen in the population. The objective of this study was to analyze the variability of the HBV preCore/Core region circulating among pregnant women in the Republic of Guinea. Materials and methods. The study material included 480 plasma samples obtained from HBV-positive pregnant women from the Republic of Guinea. For all samples, the nucleotide sequences of the preCore/Core region of the HBV genome were sequenced and analyzed. Results. Amino acid variability in the preCore region was determined in 211 (43.96%), and in the Core region in 473 (98.54%) patients. 12 polymorphic sites of the preCore region were identified in which amino acid substitutions occurred, including 8, 2 and 5 positions identified for genotypes E, A and D, respectively. In the Core region, 67 substitution positions were identified, including 46 in samples of genotype E, 23 in HBV genotype A and 26 in genotype D. It was shown that the distribution of substitutions in the preCore and Core regions in HBV genotypes E, A and D differs significantly with a predominance in mutations among HBV genotype E — p 0.0001. Individual characteristic mutations have been identified for each genotype. The most common clinically significant mutations in the preCore/Core region in the study group were identified, including pc-H5D (27,08%), pc-W28* (35,21%), c-E64D (33,54%), c-L116I/V/G (91,46 %), c-T146N (73,13%). The double mutation A1762T/G1764A in the basal core promoter was shown in 74 samples of HBV genotype E, which accounted for 15.42% of the total group and 16.59% of patients with HBV genotype E. Conclusion. The frequency of clinically significant preCore/Core mutations among pregnant women in the Republic of Guinea was determined. The data obtained reflect their prevalence in the general population and can be used to predict the progression of chronic HBV among the region's population. Collapse

Chen J, Li L, Yin Q, Shen T. A review of epidemiology and clinical relevance of Hepatitis B virus genotypes and subgenotypes. Clin Res Hepatol Gastroenterol 2023;47:102180. [PMID: 37479136 DOI: 10.1016/j.clinre.2023.102180] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 07/07/2023] [Accepted: 07/13/2023] [Indexed: 07/23/2023]

Anabire NG, Quaye O, Helegbe GK. Circulation of multiple hepatitis B virus genotypes in individual pregnant women seeking antenatal care in northern Ghana. Virol J 2023;20:149. [PMID: 37443015 PMCID: PMC10347747 DOI: 10.1186/s12985-023-02110-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 06/30/2023] [Indexed: 07/15/2023] Open

Kafeero HM, Ndagire D, Ocama P, Kato CD, Wampande E, Walusansa A, Kajumbula H, Kateete D, Ssenku JE, Sendagire H. Mapping hepatitis B virus genotypes on the African continent from 1997 to 2021: a systematic review with meta-analysis. Sci Rep 2023;13:5723. [PMID: 37029173 PMCID: PMC10082212 DOI: 10.1038/s41598-023-32865-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 04/04/2023] [Indexed: 04/09/2023] Open

Abstract

Hepatitis B virus (HBV) has ten genotypes (A-J) and over 40 sub-genotypes based on the divergence of ≥ 8% and 4 to < 8% in the complete genome respectively. These genotypes and sub-genotypes influence the disease prognosis, response to therapy and route of viral transmission. Besides, infection with mixed genotypes and recombinant genotypes has also been reported. This study aimed at mapping the de novo genotypes and correlate them with the immigration trends in order to inform future research on the underlying reasons for the relative distribution of HBV genotypes from a large sample size pooled from many primary studies. Data was extracted from 59 full research articles obtained from Scopus, PubMed, EMBASE, Willy library, African Journal Online (AJOL) and Google Scholar. Studies that investigated the genotypes, sub-genotypes, mixed genotypes and recombinant were included. The Z-test and regression were used for the analysis. The study protocol is registered with PROSPERO under the registration number CRD42022300220. Overall, genotype E had the highest pooled prevalence significantly higher than all the other genotypes (P < 0.001). By region, genotype A posted the highest pooled prevalence in eastern and southern Africa, E in west Africa and D in north Africa (P < 0.0001). Regarding the emerging genotypes B and C on the African continent, genotype B was significantly higher in south Africa than C (P < 0.001). In contrast, genotype C was significantly higher in east Africa than west Africa (P < 0.0001). The A1 and D/E were the most diverse sub-genotypes and genotype mixtures respectively. Finally, we observed a general progressive decrease in the prevalence of predominant genotypes but a progressive increase in the less dominant by region. Historical and recent continental and intercontinental migrations can provide a plausible explanation for the HBV genotype distribution pattern on the African continent.

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A novel subgenotype I3 of hepatitis B virus in Guangxi, China: a 15-year follow-up study. Virus Genes 2023;59:359-369. [PMID: 36841897 DOI: 10.1007/s11262-023-01980-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 02/13/2023] [Indexed: 02/27/2023]

Dagnew M, Moges F, Tiruneh M, Million Y, Gelaw A, Adefris M, Belyhun Y, Liebert UG, Maier M. Molecular diversity of hepatitis B virus among pregnant women in Amhara National Regional State, Ethiopia. PLoS One 2022;17:e0276687. [PMID: 36378635 PMCID: PMC9665361 DOI: 10.1371/journal.pone.0276687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Accepted: 10/11/2022] [Indexed: 11/17/2022] Open

Abstract

Background

Despite the availability of effective vaccines and treatments for hepatitis B virus (HBV), it continues to be a major public health problem in sub-Saharan Africa including Ethiopia. Routine screening for HBV in pregnant women is widely recommended, but there is lack of screening for HBV during pregnancy in Ethiopia. Therefore, this study aimed to assess viral load, and genetic diversity among pregnant women in the Amhara National Regional State, Ethiopia.

Materials and methods

Hepatitis B surface antigen (HBsAg) testing was performed on 1846 pregnant women, 85 of who tested positive were included in this study. HBV DNA was isolated from 85 positive sera, and the partial surface/polymerase gene was amplified and sequenced. HBV genotypes, sub-genotypes, serotypes and mutations in surface genes and polymerase were studied.

Results

Out of 85 pregnant women`s HBsAg positive sera, 59(69.4%) had detectable viral DNA. The median viral load was 3.4 log IU/ml ranging from 2.6 to7.6 and 46 samples were successfully sequenced and genotyped. Genotypes A and D were identified in 39 (84.8%) and 7 (15.2%); respectively. All genotype A isolates were further classified into sub-genotype A1 and serotype adw2 (84.8%) whereas genotype D isolates were further classified into three sub genotypes; 2 (4.3%) D2, 1(2.2%) D4, and 4 (8.7%) D10 with serotypes ayw2 (10.9%), and ayw3 (4.3%). There were 19 (41.3%) surface gene mutations in the major hydrophilic region (MHR). Six (13.1%) of them were discovered in MHR`s `a’-determinant region. Six polymerase gene mutations (13%) were identified.

Conclusion

Genotype A was the predominant genotype in the Amhara National Regional State. The surface and polymerase gene mutations identified in this study may lead to immune therapy failure, diagnostics escape and drug resistance. Thus, the data generated in this study will contribute to the planning of HBV diagnosis, vaccination and treatment, and most importantly to the prevention of vertical transmission of HBV in Ethiopia. Therefore, further molecular studies on HBV are warranted and continuous surveillance is important for patient management and for the prevention and control of HBV infection in the country.

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Spearman CW, Dusheiko G, Jonas E, Abdo A, Afihene M, Cunha L, Desalegn H, Kassianides C, Katsidzira L, Kramvis A, Lam P, Lesi OA, Micah EA, Musabeyezu E, Ndow G, Nnabuchi CV, Ocama P, Okeke E, Rwegasha J, Shewaye AB, Some FF, Tzeuton C, Sonderup MW. Hepatocellular carcinoma: measures to improve the outlook in sub-Saharan Africa. Lancet Gastroenterol Hepatol 2022;7:1036-1048. [PMID: 35810766 DOI: 10.1016/s2468-1253(22)00041-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 01/26/2022] [Accepted: 02/02/2022] [Indexed: 02/08/2023]

Affiliation(s)

C Wendy Spearman Division of Hepatology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Geoffrey Dusheiko University College London Medical School, London, UK; Kings College Hospital, London, UK
Eduard Jonas Surgical Gastroenterology Unit, Division of General Surgery, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Abdelmounem Abdo National Centre for Gastrointestinal and Liver Disease, Ibn Sina Hospital, Alamarat, Khartoum, Sudan
Mary Afihene Department of Medicine, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Lina Cunha Gastroenterology Unit, Maputo Private Hospital, Maputo, Mozambique
Hailemichael Desalegn Department of Internal Medicine, St Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
Chris Kassianides Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Leolin Katsidzira Internal Medicine Unit, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe
Anna Kramvis Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa
Philip Lam Clinique Darné, Curepipe, Mauritius
Olufunmilayo A Lesi Gastroenterology and Hepatology Unit, College of Medicine, University of Lagos, Lagos, Nigeria
Eileen A Micah Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana
Emmanuel Musabeyezu Department of Medicine, King Faisal Hospital, Kigali, Rwanda
Gibril Ndow Disease Control and Elimination Theme, MRC Unit The Gambia at the London School of Tropical Medicine, London, UK; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
Chidi V Nnabuchi Asokoro District Hospital, Nile University Teaching Hospital, Abuja, Nigeria
Ponsiano Ocama School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
Edith Okeke Gastroenterology and Hepatology Unit, Department of Internal Medicine, College of Health Sciences, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
John Rwegasha Gastroenterology Training Centre, Department of Internal Medicine, Muhimbili National Hospital, Dar Es Salaam, Tanzania
Abate B Shewaye Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
Fatuma F Some Department of Medicine, School of Medicine, College of Health Sciences, Moi University, Eldoret, Kenya
Christian Tzeuton Faculty of Medicine and Pharmaceutical Sciences of Douala, University of Douala, Douala, Cameroon
Mark W Sonderup Division of Hepatology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

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Maepa MB, Ely A, Kramvis A, Bloom K, Naidoo K, Simani OE, Maponga TG, Arbuthnot P. Hepatitis B Virus Research in South Africa. Viruses 2022;14:v14091939. [PMID: 36146747 PMCID: PMC9503375 DOI: 10.3390/v14091939] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 08/11/2022] [Accepted: 08/26/2022] [Indexed: 11/18/2022] Open

Roberts LR. Untreated Chronic Hepatitis B Is Associated With a Higher Risk of Extrahepatic Malignancies. J Clin Oncol 2022;40:3357-3360. [DOI: 10.1200/jco.22.01051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open

Disproportionate Distribution of HBV Genotypes A and D and the Recombinant Genotype D/E in the High and Low HBV Endemic Regions of Uganda: A Wake-Up Call for Regional Specific HBV Management. Int J Hepatol 2022;2022:3688547. [PMID: 35070455 PMCID: PMC8767397 DOI: 10.1155/2022/3688547] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 11/08/2021] [Accepted: 12/17/2021] [Indexed: 12/15/2022] Open

Abstract

BACKGROUND

Hepatitis B virus (HBV) is the leading cause of liver-related diseases. In Uganda, there is a regional disparity in the HBV burden. Our study was aimed at establishing the circulating genotypes in a low and a high endemic region to give plausible explanations for the differences in regional burden and guide the future management of the disease.

METHODS

A total of 200 HBsAg-seropositive subjects were recruited into the study by convenience sampling. The HBsAg Rapid Test Strip (Healgen Scientific Limited Liability Company, Houston, TX77047- USA) was used to screen for HBsAg while the Roche machine (Roche, Basel Switzerland/Abbot Technologies (USA)) was used to determine the viral load. The Chemistry Analyzer B120 (Mindray, China) was used for chemistry analysis. For HBV genotyping, total DNA was extracted from whole blood using the QIAamp® DNA extraction kit. Nested PCR amplification was performed using Platinum Taq DNA Polymerase (Invitrogen Corporation, USA) to amplify the 400 bp HBV polymerase gene. Purification of nested PCR products was performed using Purelink PCR product purification kit (Life Technologies, USA). Automated DNA sequencing was performed using BigDye Terminator v3.1 Cycle Sequencing Kit on 3130 Genetic Analyzer (Applied Biosystems, USA). The NCBI HBV genotyping tool (https://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi) was used for determination of genotype for each HBV sequence. Pearson's chi-square, multinomial logistic regression, and Mann-Whitney U tests were used for the analysis. All the analyses were done using SPSS version 26.0 and MedCalc software version 19.1.3 at 95% CI. A p < 0.05 was considered statistically significant.

RESULTS

Majority of our study subjects were female (64.5%), youth (51.0%), and married (62.0%). Overall, genotype A was the most prevalent (46%). Genotype D and the recombinant genotype D/E were proportionately more distributed in the high endemic (38.2%) and low endemic (36.5%) regions, respectively. Genotype D was significantly more prevalent in the high endemic region and among the elderly (p < 0.05). Genotype D was significantly associated with elevated viral load and direct bilirubin (p < 0.05). The recombinant genotype D/E was significantly associated with elevated viral load (p < 0.05). Similarly, genotype A was significantly associated with elevated AST and GGT, lowered viral load, and normal direct bilirubin levels (p < 0.05).

CONCLUSION

There is disproportionate distribution of genotypes A and D and the recombinant genotype D/E in the low and high endemic regions of Uganda. This probably could explain the differences in endemicity of HBV in our country signifying the need for regional specific HBV management and control strategies.

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Ingasia LAO, Wose Kinge C, Kramvis A. Genotype E: The neglected genotype of hepatitis B virus. World J Hepatol 2021;13:1875-1891. [PMID: 35069995 PMCID: PMC8727212 DOI: 10.4254/wjh.v13.i12.1875] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 06/15/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open

In Vivo Modelling of Hepatitis B Virus Subgenotype A1 Replication Using Adeno-Associated Viral Vectors. Viruses 2021;13:v13112247. [PMID: 34835053 PMCID: PMC8618177 DOI: 10.3390/v13112247] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 10/30/2021] [Accepted: 11/04/2021] [Indexed: 12/23/2022] Open

Interpretation of HBV Serologies. Clin Liver Dis 2021;25:689-709. [PMID: 34593148 DOI: 10.1016/j.cld.2021.06.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]

Hayashi S, Nagaoka K, Tanaka Y. Blood-Based Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma, Including the Viral Genome and Glycosylated Proteins. Int J Mol Sci 2021;22:11051. [PMID: 34681709 PMCID: PMC8540379 DOI: 10.3390/ijms222011051] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 10/08/2021] [Accepted: 10/11/2021] [Indexed: 12/12/2022] Open

Challenges for hepatitis B virus cure in resource-limited settings in sub-Saharan Africa. Curr Opin HIV AIDS 2021;15:185-192. [PMID: 32141888 DOI: 10.1097/coh.0000000000000619] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]

In vitro expression of precore proteins of hepatitis B virus subgenotype A1 is affected by HBcAg, and can affect HBsAg secretion. Sci Rep 2021;11:8167. [PMID: 33854155 PMCID: PMC8046783 DOI: 10.1038/s41598-021-87529-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 03/30/2021] [Indexed: 12/16/2022] Open

Abstract

HBeAg, a non-particulate protein of hepatitis B virus (HBV), is translated from the precore/core region as a precursor, which is post-translationally modified. Subgenotype A1 of HBV, which is a risk factor for hepatocellular carcinoma (HCC), has unique molecular characteristics in the basic core promoter/precore regions. Carriers of A1 exhibit early HBeAg loss. We sought to further characterize the precore proteins of A1 in vitro. HuH-7 cells were transfected with subgenomic constructs expressing individual precore proteins. Western blot analysis using DAKO anti-core antibody showed the expected sizes and a 1 kDa larger band for P22, P20 and P17. Using confocal microscopy, a cytoplasmic accumulation of HBeAg and precursors was observed with P25-expressing plasmid, whereas P22 localized both in the cytoplasm and nucleus. P20 and P17, which lack the carboxy end of P22 showed strong nuclear accumulation, implicating a nuclear localization signal in the N-terminal 10 amino acids. G1862T, unique to subgenotype A1, is frequently found in HBV from HCC patients. P25 with G1862T showed delayed and reduced HBeAg expression/secretion. Knock-out of core in the replication competent clones led to precore protein accumulation in the cytoplasm/perinuclear region, and decreased HBeAg secretion. Knock-out of precore proteins increased HBsAg secretion but intracellular HBsAg expression was unaffected. Over-expression of precore proteins in trans led to decreased HBsAg expression and secretion. Intracellular trafficking of HBV A1 precore proteins was followed. This was unaffected by the CMV promoter and different cell types. In the viral context, precore protein expression was affected by absence of core, and affected HBsAg expression, suggesting an interrelationship between precore proteins, HBcAg and HBsAg. This modulatory role of HBeAg and its precursors may be important in viral persistence and ultimate development of HCC.

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Araujo NM, Teles SA, Spitz N. Comprehensive Analysis of Clinically Significant Hepatitis B Virus Mutations in Relation to Genotype, Subgenotype and Geographic Region. Front Microbiol 2020;11:616023. [PMID: 33381105 PMCID: PMC7767914 DOI: 10.3389/fmicb.2020.616023] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 11/25/2020] [Indexed: 12/14/2022] Open

Abstract

Hepatitis B virus (HBV) is a highly variable DNA virus due to its unique life cycle, which involves an error-prone reverse transcriptase. The high substitution rate drives the evolution of HBV by generating genetic variants upon which selection operates. HBV mutants with clinical implications have been documented worldwide, indicating the potential for spreading and developing their own epidemiology. However, the prevalence of such mutants among the different HBV genotypes and subgenotypes has not been systematically analyzed. In the current study, we performed large-scale analysis of 6,479 full-length HBV genome sequences from genotypes A-H, with the aim of gaining comprehensive insights into the relationships of relevant mutations associated with immune escape, antiviral resistance and hepatocellular carcinoma (HCC) development with HBV (sub)genotypes and geographic regions. Immune escape mutations were detected in 10.7% of the sequences, the most common being I/T126S (1.8%), G145R (1.2%), M133T (1.2%), and Q129R (1.0%). HBV genotype B showed the highest rate of escape mutations (14.7%) while genotype H had no mutations (P < 0.001). HCC-associated mutations were detected in 33.7% of the sequences, with significantly higher frequency of C1653T, T1753V and A1762T/G1764A in genotype G than C (P < 0.001). The overall frequencies of lamivudine-, telbivudine-, adefovir-, and entecavir-resistant mutants were 7.3, 7.2, 0.5, and 0.2%, respectively, while only 0.05% showed reduced susceptibility to tenofovir. In particular, the highest frequency of lamivudine-resistant mutations was observed in genotype G and the lowest frequency in genotype E (32.5 and 0.3%; P < 0.001). The prevalence of HBV mutants was also biased by geographic location, with North America identified as one of the regions with the highest rates of immune escape, antiviral resistance, and HCC-associated mutants. The collective findings were discussed in light of natural selection and the known characteristics of HBV (sub)genotypes. Our data provide relevant information on the prevalence of clinically relevant HBV mutations, which may contribute to further improvement of diagnostic procedures, immunization programs, therapeutic protocols, and disease prognosis.

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Kabamba AT, Kalunga BT, Mwamba CM, Nyembo CM, Dufrasne F, Dessilly G, Kabamba BM, Longanga AO. Epidemiological aspects and molecular characterization of the hepatitis B virus among blood donors in Lubumbashi, Democratic Republic of Congo. Transfus Clin Biol 2020;28:30-37. [PMID: 33232802 DOI: 10.1016/j.tracli.2020.10.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 10/18/2020] [Accepted: 10/30/2020] [Indexed: 01/09/2023]

Cohen D, Ghosh S, Shimakawa Y, Ramou N, Garcia PS, Dubois A, Guillot C, Kakwata-Nkor Deluce N, Tilloy V, Durand G, Voegele C, Ndow G, d'Alessandro U, Brochier-Armanet C, Alain S, Le Calvez-Kelm F, Hall J, Zoulim F, Mendy M, Thursz M, Lemoine M, Chemin I. Hepatitis B virus preS2Δ38-55 variants: A newly identified risk factor for hepatocellular carcinoma. JHEP Rep 2020;2:100144. [PMID: 32904132 PMCID: PMC7452365 DOI: 10.1016/j.jhepr.2020.100144] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 06/25/2020] [Accepted: 07/02/2020] [Indexed: 02/07/2023] Open

Abstract

BACKGROUND & AIMS

Although HBV is a major cause of death in Africa, its genetic variability has been poorly documented. This study aimed to address whether HBV genotype and surface gene variants are associated with HBV-related liver disease in The Gambia.

METHODS

We conducted a case-control study nested in the Prevention of Liver Fibrosis and Cancer in Africa programme. Consecutive treatment-naive patients with chronic HBV infection and detectable viral load were recruited: 211 controls with no significant liver disease and 91 cases (56 cirrhosis and 35 HCC cases). HBV genotypes and surface gene variants were determined by Sanger sequencing or next-generation sequencing (NGS) in serum DNA. Aflatoxin B1 (AFB1)-specific codon 249 TP53 mutation was determined by NGS in circulating cell-free plasma DNA.

RESULTS

In phylogenetic analysis, 85% of individuals carried HBV genotype E, 14% genotype A, and 1% A/E recombinant viruses. Surface gene variants were more frequently observed in cases (43% and 57% in cirrhosis and HCC cases, respectively) than controls (25%; p <0.001), with preS2 deletions between nucleotides 38-55 (preS2Δ38-55) being the main genetic variant detected. In multivariable analysis, HBeAg seropositivity, low HBsAg levels, and HDV seropositivity were significantly associated with cirrhosis and HCC, whilst older age, higher viral load, genotype A, preS2Δ38-55, and AFB1 exposure were only associated with HCC. There was a multiplicative joint effect of preS2Δ38-55 variants with HBeAg seropositivity (odds ratio [OR] 43.1 [10.4-177.7]), high viral load >2,000 IU/ml (OR 22.7 [8.0-64.9]), HBsAg levels <10,000 IU/ml (OR 19.0 [5.5-65.3]), and AFB1 exposure (OR 29.3 [3.7-230.4]) on HCC risk.

CONCLUSIONS

This study identified a hotspot for HBV preS2 deletions as a strong independent factor for HCC in The Gambia, with HBV genotypes and AFB1 exposure contributing to the high liver cancer risk.

LAY SUMMARY

Although HBV-related liver disease is highly prevalent in sub-Saharan Africa, the associated virological characteristics are poorly studied. Using clinical data from African patients chronically infected with HBV, an assessment of the virological variability (genotypes and mutations) and exposure to AFB1, a toxin often contaminating food, was carried out. Our results show that HBV genotypes, the presence of a highly prevalent mutant form of HBV, and AFB1 exposure contribute to the high liver cancer risk in this population.

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Affiliation(s)

Damien Cohen INSERM U1052, CNRS 5286, Univ Lyon, Université Claude Bernard Lyon 1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France
Sumantra Ghosh INSERM U1052, CNRS 5286, Univ Lyon, Université Claude Bernard Lyon 1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France
Yusuke Shimakawa Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France
Njie Ramou International Agency for Research on Cancer, Lyon, France
Pierre Simon Garcia Univ Lyon, Université Lyon 1, CNRS, UMR5558, Laboratoire de Biométrie et Biologie Évolutive, Villeurbanne, France Molecular Microbiology and Structural Biochemistry, Institut de Biologie et de Chimie des Protéines 7 passage du Vercors, Lyon Cedex, France
Anaëlle Dubois INSERM U1052, CNRS 5286, Univ Lyon, Université Claude Bernard Lyon 1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France
Clément Guillot INSERM U1052, CNRS 5286, Univ Lyon, Université Claude Bernard Lyon 1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France
Nora Kakwata-Nkor Deluce INSERM U1052, CNRS 5286, Univ Lyon, Université Claude Bernard Lyon 1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France
Valentin Tilloy Microbiology Department, CHU Limoges, Genomic Platform GenoLim, UMR Inserm 1092/FR CNRS 145 GEIST, Faculté de Médecine-Université de Limoges, CHU Dupuytren, CBRS, Limoges, France
Geoffroy Durand International Agency for Research on Cancer, Lyon, France
Catherine Voegele International Agency for Research on Cancer, Lyon, France
Gibril Ndow Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia
Umberto d'Alessandro Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia
Céline Brochier-Armanet Univ Lyon, Université Lyon 1, CNRS, UMR5558, Laboratoire de Biométrie et Biologie Évolutive, Villeurbanne, France
Sophie Alain Microbiology Department, CHU Limoges, Genomic Platform GenoLim, UMR Inserm 1092/FR CNRS 145 GEIST, Faculté de Médecine-Université de Limoges, CHU Dupuytren, CBRS, Limoges, France
Florence Le Calvez-Kelm International Agency for Research on Cancer, Lyon, France
Janet Hall INSERM U1052, CNRS 5286, Univ Lyon, Université Claude Bernard Lyon 1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France
Fabien Zoulim INSERM U1052, CNRS 5286, Univ Lyon, Université Claude Bernard Lyon 1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France Department of Hepatology, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France
Maimuna Mendy International Agency for Research on Cancer, Lyon, France
Mark Thursz Department of Metabolism, Digestion and Reproduction, Liver Unit, Imperial College London, London, UK
Maud Lemoine Department of Metabolism, Digestion and Reproduction, Liver Unit, Imperial College London, London, UK
Isabelle Chemin INSERM U1052, CNRS 5286, Univ Lyon, Université Claude Bernard Lyon 1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France

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Maponga TG, Glashoff RH, Vermeulen H, Robertson B, Burmeister S, Bernon M, Omoshoro-Jones J, Ruff P, Neugut AI, Jacobson JS, Preiser W, Andersson MI. Hepatitis B virus-associated hepatocellular carcinoma in South Africa in the era of HIV. BMC Gastroenterol 2020;20:226. [PMID: 32660431 PMCID: PMC7359588 DOI: 10.1186/s12876-020-01372-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 07/07/2020] [Indexed: 02/08/2023] Open

Abstract

BACKGROUND

Patients co-infected with hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are at risk of developing hepatocellular carcinoma (HCC). In sub-Saharan Africa, the overlap between high HIV and HBV prevalence may increase the incidence of HCC. This study investigated the impact of HBV/HIV co-infection on age at presentation and survival of HCC.

METHODS

Ethical approval was obtained to recruit, following informed written consent, patients diagnosed with HCC at oncology units at four South African hospitals. Between December 2012 and August 2015, patients newly diagnosed with HCC were recruited and provided demographic and clinical data and blood specimens. Patients were tested for HBV, hepatitis C virus (HCV) and HIV. Survival data was available for a subset of patients.

RESULTS

Of 107 HCC cases, 83 (78%) were male. Median age was 46 years (range 18 to 90 years), 68/106 (64%) were HBsAg-positive, and 22/100 (22%) were HIV infected. Among HBV surface antigen (HBsAg)-positive HCC cases, 18/66 (27%) were HIV-infected compared to 3/34 (9%) among those that were HBsAg-negative (p = 0.04). A greater proportion of HBV/HIV co-infected cases were female than HBV mono-infected (6/18, 33% vs 6/47, 13%; p = 0.005). In addition, HBV/HIV co-infected females presented at a younger mean age (36.8 years) than HBV mono-infected women (50.5 years) (p = 0.09). Median survival was 82 days among the HIV-infected HCC patients compared to 181 days among those without HIV (p = 0.15).

CONCLUSIONS

HCC is an important complication in the HIV/HBV infected patient. HIV-positive patients presented with HCC at a younger age than HIV-negative patients, this effect appears to be greater in women. These data provide more evidence supporting the call to address. HCC as a cause of morbidity and mortality in the HBV/HIV co-infected patient population. (281 words).

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Affiliation(s)

Tongai Gibson Maponga Division of Medical Virology, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town, South Africa.
Richard H Glashoff Division of Medical Microbiology & Immunology, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town, South Africa.,Tygerberg Business Unit, National Health Laboratory Service, Cape Town, South Africa
Hannali Vermeulen Division of Radiation Oncology, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town, South Africa
Barbara Robertson Division of Radiation Oncology, University of Cape Town, Cape Town, South Africa
Sean Burmeister Department of Surgery, University of Cape Town, Cape Town, South Africa
Marc Bernon Department of Surgery, University of Cape Town, Cape Town, South Africa
Jones Omoshoro-Jones Department of Surgery, University of Witwatersrand, Johannesburg, South Africa
Paul Ruff Division of Medical Oncology, University of Witwatersrand, Johannesburg, South Africa
Alfred I Neugut Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, USA.,Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, USA.,Mailman School of Public Health, Columbia University, New York, USA
Judith S Jacobson Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, USA.,Mailman School of Public Health, Columbia University, New York, USA
Wolfgang Preiser Division of Medical Virology, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town, South Africa.,Tygerberg Business Unit, National Health Laboratory Service, Cape Town, South Africa
Monique I Andersson Division of Medical Virology, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town, South Africa.,Department of Microbiology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

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Mak D, Kramvis A. Molecular characterization of hepatitis B virus isolated from Black South African cancer patients, with and without hepatocellular carcinoma. Arch Virol 2020;165:1815-1825. [PMID: 32504396 DOI: 10.1007/s00705-020-04686-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 04/29/2020] [Indexed: 12/16/2022]

Sonderup MW, Dusheiko G, Desalegn H, Lemoine M, Tzeuton C, Taylor-Robinson SD, Spearman CW. Hepatitis B in sub-Saharan Africa-How many patients need therapy? J Viral Hepat 2020;27:560-567. [PMID: 31800145 DOI: 10.1111/jvh.13247] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Accepted: 11/07/2019] [Indexed: 12/13/2022]

Vinikoor MJ, Sinkala E, Kanunga A, Muchimba M, Zanolini A, Saag M, Pry J, Nsokolo B, Chisenga T, Kelly P. Eligibility for hepatitis B antiviral therapy among adults in the general population in Zambia. PLoS One 2020;15:e0227041. [PMID: 31929556 PMCID: PMC6957183 DOI: 10.1371/journal.pone.0227041] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 12/10/2019] [Indexed: 01/26/2023] Open

Abstract

INTRODUCTION

We evaluated antiviral therapy (AVT) eligibility in a population-based sample of adults with chronic hepatitis B virus (HBV) infection in Zambia.

MATERIALS AND METHODS

Using a household survey, adults (18+ years) were tested for hepatitis B surface antigen (HBsAg). Sociodemographic correlates of HBsAg-positivity were identified with multivariable regression. HBsAg-positive individuals were referred to a central hospital for physical examination, elastography, and phlebotomy for HBV DNA, hepatitis B e antigen, serum transaminases, platelet count, and HIV-1/2 antibody. We determined the proportion of HBV monoinfected adults eligible for antiviral therapy (AVT) based on European Association for the Study of the Liver (EASL) 2017 guidelines. We also evaluated the performance of two alternative criteria developed for use in sub-Saharan Africa, the World Health Organization (WHO) and Treat-B guidelines.

RESULTS

Across 12 urban and 4 rural communities, 4,961 adults (62.9% female) were tested and 182 (3.7%) were HBsAg-positive, 80% of whom attended hospital follow-up. HBsAg-positivity was higher among men (adjusted odds ratio [AOR], 1.37; 95% confidence interval [CI], 0.99-1.87) and with decreasing income (AOR, 0.89 per household asset; 95% CI, 0.81-0.98). Trends toward higher HBsAg-positivity were also seen at ages 30-39 years (AOR, 2.11; 95% CI, 0.96-4.63) and among pregnant women (AOR, 1.74; 95% CI, 0.93-3.25). Among HBV monoinfected individuals (i.e., HIV-negative) evaluated for AVT, median age was 31 years, 24.6% were HBeAg-positive, and 27.9% had HBV DNA >2,000 IU/ml. AVT-eligibility was 17.0% by EASL, 10.2% by WHO, and 31.1% by Treat-B. Men had increased odds of eligibility. WHO (area under the receiver operating curve [AUROC], 0.68) and Treat-B criteria (AUROC, 0.76) had modest accuracy. Fourteen percent of HBsAg-positive individuals were HIV coinfection, and most coinfected individuals were taking tenofovir-containing antiretroviral therapy (ART).

CONCLUSION

Approximately 1 in 6 HBV monoinfected adults in the general population in Zambia may be AVT-eligible. Men should be a major focus of hepatitis B diagnosis and treatment. Further development and evaluation of HBV treatment criteria for resource-limited settings is needed. In settings with overlapping HIV and HBV epidemics, scale-up of ART has contributed towards hepatitis B elimination.

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Bannister E, Sozzi V, Mason H, Locarnini S, Hardikar W, Revill PA. Analysis of the in vitro replication phenotype of African hepatitis B virus (HBV) genotypes and subgenotypes present in Australia identifies marked differences in DNA and protein expression. Virology 2019;540:97-103. [PMID: 31765921 DOI: 10.1016/j.virol.2019.11.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 11/01/2019] [Accepted: 11/01/2019] [Indexed: 02/06/2023]

Revill PA, Penicaud C, Brechot C, Zoulim F. Meeting the Challenge of Eliminating Chronic Hepatitis B Infection. Genes (Basel) 2019;10:genes10040260. [PMID: 30939846 PMCID: PMC6523454 DOI: 10.3390/genes10040260] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 01/29/2019] [Accepted: 02/01/2019] [Indexed: 12/14/2022] Open

Coffin CS, Fung SK, Alvarez F, Cooper CL, Doucette KE, Fournier C, Kelly E, Ko HH, Ma MM, Martin SR, Osiowy C, Ramji A, Tam E, Villeneuve JP. Management of Hepatitis B Virus Infection: 2018 Guidelines from the Canadian Association for the Study of Liver Disease and Association of Medical Microbiology and Infectious Disease Canada. CANADIAN LIVER JOURNAL 2018;1:156-217. [PMID: 35992619 PMCID: PMC9202759 DOI: 10.3138/canlivj.2018-0008] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 04/17/2018] [Indexed: 08/01/2023]

Cuenca-Gómez JÁ, Lozano-Serrano AB, Cabezas-Fernández MT, Soriano-Pérez MJ, Vázquez-Villegas J, Estévez-Escobar M, Cabeza-Barrera I, Salas-Coronas J. Chronic hepatitis B genotype E in African migrants: response to nucleos(t)ide treatment in real clinical practice. BMC Infect Dis 2018;18:568. [PMID: 30428845 PMCID: PMC6236963 DOI: 10.1186/s12879-018-3469-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2018] [Accepted: 10/31/2018] [Indexed: 12/18/2022] Open

Abstract

Background

Hepatitis B virus (HBV) genotype E is a poorly studied genotype that almost exclusively occurs in African people. It seems to harbour intrinsic potential oncogenic activity and virological characteristics of immune scape but a paucity of information is available on clinical and virological characteristic of HBV genotype E-infected patients as well as on the efficacy of anti-HBV drugs for such patients. The increasing flow of migrants from high endemic HBV sub-Saharan Africa, where genotype E is the predominant one, to Western countries makes improving such knowledge critical in order to deliver proper medical care.

Methods

Prospective observational study of naïve patients of sub-Saharan origin treated for chronic HBV genotype E infection at a Tropical Medicine clinic sited in Spain from February 2004 to January 2018. The aim of the study was to describe the response of chronic HBV genotype E infection to nucleos(t)ide analogues (NA), entecavir or tenofovir, in real clinical practice.

Results

During the study period, 2209 sub-Saharan patients were assisted at our Tropical Medicine Unit and 609 (27.6%) had chronic HBV (CHB) infection. Genotype information was available for 55 naïve patients initiating treatment with NA (entecavir or tenofovir), 43 (84.3%) of them being genotype E, although 15 were excluded because they did not meet study inclusion criteria. Thus, a total of 28 CHB genotype E patients were included and followed for 24 months at least. Twenty-one patients were in HBeAg-negative chronic hepatitis phase and 7 patients in HBeAg-positive chronic hepatitis phase. After one year of treatment, among those with good adherence, 89.4% (17/19) of the HBeAg-negative patients and 80% of the HBeAg-positive ones had undetectable viral loads. Response rates reached 100% in both groups after 15–18 months of follow-up. Out of the 7 HBeAg-positive patients, 6 (85.7%) presented HBeAg loss in a median time of 31.8 months. Neither serious adverse effects nor hepatocarcinoma cases happened during the study period.

Conclusions

HBV genotype may influence disease progression and antiviral response. Our study provides precious information on the efficacy and safety of NA treatment for CHB genotype E infection, a fairly unknown genotype with and increasing epidemiological impact.

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Kostaki EG, Karamitros T, Stefanou G, Mamais I, Angelis K, Hatzakis A, Kramvis A, Paraskevis D. Unravelling the history of hepatitis B virus genotypes A and D infection using a full-genome phylogenetic and phylogeographic approach. eLife 2018;7:36709. [PMID: 30082021 PMCID: PMC6118819 DOI: 10.7554/elife.36709] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Accepted: 07/28/2018] [Indexed: 12/17/2022] Open

Global HBV burden: guesstimates and facts. Hepatol Int 2018;12:315-329. [DOI: 10.1007/s12072-018-9884-8] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Accepted: 07/05/2018] [Indexed: 12/14/2022]

Bannister EG, Yuen L, Littlejohn M, Edwards R, Sozzi V, Colledge D, Li X, Locarnini S, Hardikar W, Revill PA. Molecular characterization of hepatitis B virus (HBV) in African children living in Australia identifies genotypes and variants associated with poor clinical outcome. J Gen Virol 2018;99:1103-1114. [PMID: 29932395 DOI: 10.1099/jgv.0.001086] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open

Affiliation(s)

Elizabeth G Bannister 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia.,2Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Parkville, Victoria, Australia.,3Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia
Lilly Yuen 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia
Margaret Littlejohn 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia
Rosalind Edwards 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia
Vitina Sozzi 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia
Danni Colledge 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia
Xin Li 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia
Stephen Locarnini 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia
Winita Hardikar 2Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Parkville, Victoria, Australia.,3Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia
Peter A Revill 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia.,4Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia

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Khatun M, Mondal RK, Pal S, Baidya A, Bishnu D, Banerjee P, Santra AK, Dhali GK, Banerjee S, Chowdhury A, Datta S. Distinctiveness in virological features and pathogenic potentials of subgenotypes D1, D2, D3 and D5 of Hepatitis B virus. Sci Rep 2018;8:8055. [PMID: 29795338 PMCID: PMC5966457 DOI: 10.1038/s41598-018-26414-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Accepted: 05/11/2018] [Indexed: 12/13/2022] Open

Affiliation(s)

Mousumi Khatun Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research (I.P.G.M.E. & R.), Kolkata, India
Rajiv Kumar Mondal Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research (I.P.G.M.E. & R.), Kolkata, India
Sourina Pal Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research (I.P.G.M.E. & R.), Kolkata, India
Ayana Baidya Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research (I.P.G.M.E. & R.), Kolkata, India
Debasree Bishnu Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research (I.P.G.M.E. & R.), Kolkata, India
Priyanka Banerjee Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research (I.P.G.M.E. & R.), Kolkata, India
Amal Kumar Santra Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research (I.P.G.M.E. & R.), Kolkata, India
Gopal Krishna Dhali Department of Gastroenterology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research (I.P.G.M.E. & R.), Kolkata, India
Soma Banerjee Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research (I.P.G.M.E. & R.), Kolkata, India
Abhijit Chowdhury Department of Hepatology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research (I.P.G.M.E. & R.), Kolkata, India
Simanti Datta Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research (I.P.G.M.E. & R.), Kolkata, India.

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Kilonzo SB, Gunda DW, Mpondo BCT, Bakshi FA, Jaka H. Hepatitis B Virus Infection in Tanzania: Current Status and Challenges. J Trop Med 2018;2018:4239646. [PMID: 29666656 PMCID: PMC5831599 DOI: 10.1155/2018/4239646] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Revised: 12/18/2017] [Accepted: 01/03/2018] [Indexed: 12/13/2022] Open

Virological and Clinical Characteristics of Hepatitis B Virus Genotype A. J Gastroenterol 2018;53:18-26. [PMID: 28687901 DOI: 10.1007/s00535-017-1367-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Accepted: 06/30/2017] [Indexed: 02/04/2023]

Deressa T, Damtie D, Fonseca K, Gao S, Abate E, Alemu S, Aleka Y, Swain MG, van Marle G, Coffin CS. The burden of hepatitis B virus (HBV) infection, genotypes and drug resistance mutations in human immunodeficiency virus-positive patients in Northwest Ethiopia. PLoS One 2017;12:e0190149. [PMID: 29281718 PMCID: PMC5744989 DOI: 10.1371/journal.pone.0190149] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Accepted: 12/09/2017] [Indexed: 12/24/2022] Open

Abstract

Background

In sub-Saharan Africa, the hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections are endemic. Although there has been great progress in HIV care, universal HBV vaccination and care is lacking. In this study, we aimed to determine the prevalence of HBV, HBV genotypes, and drug resistance mutations in dual infected cases in a cohort of HIV patients in Northwest Ethiopia.

Methods

A total of 308 HIV-1 positive patients were enrolled into the study and tested for HBsAg in plasma. In HBsAg positive samples, HBV DNA was analyzed for HBV genotype using in-house nested PCR with HBV-specific pre-core / core or surface primers, and for HBV drug resistance mutations (DRMs) in polymerase region. Odds ratio at 95% confidence interval was calculated.

Results

Of the 308 HIV-positive subjects, 62.7% were female, median age 38 years (range 18–68, IQR: 27–49), and the median CD4 count 405 cells/μl (IQR: 75–734). Overall, 94.2% were on antiretroviral therapy (ART) frequently with combinations of Zidovudine (AZT)- Lamivudine (3TC)—Nevirapine (NVP). HBsAg was detected in 5.5% (95%CI 2.95–8.08%) of the study participants, of which the majority were infected with HBV genotype A (7A, 2E, 2D, 1C, 1 G). All HIV/HBV positive cases were on ART with anti-HBV activity (i.e., 3TC) and 3TC associated HBV DRMs (i.e., rtV173L, rtL180M, and rtM204V) were detected in 7/13 (53.8%) subjects.

Conclusion

In this cross-sectional study of HIV-infected individuals, we found 5.5% HBV/HIV co-infected cases. Most were receiving the first generation anti-HBV therapy with a low genetic barrier to resistance, and several carried mutations associated with anti-HBV (3TC) drug resistance. These data underscore the importance of integrating HBV screening to the HIV treatment guidelines for better management and prevention of HBV-related liver disease.

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Affiliation(s)

Tekalign Deressa Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia * E-mail:
Debasu Damtie Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
Kevin Fonseca Provincial Laboratory for Public Health, Calgary, Alberta, Canada
Shan Gao Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
Ebba Abate Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia Ethiopian Public health institute, Addis Ababa, Ethiopia
Shitaye Alemu School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
Yetemwork Aleka Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
Mark G. Swain Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
Guido van Marle Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
Carla S. Coffin Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada

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Jaquet A, Nouaman M, Tine J, Tanon A, Anoma C, Inwoley A, Attia A, Ekouevi DK, Seydi M, Dabis F, Wandeler G. Hepatitis B treatment eligibility in West Africa: Uncertainties and need for prospective cohort studies. Liver Int 2017;37:1116-1121. [PMID: 28561454 PMCID: PMC5524454 DOI: 10.1111/liv.13484] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Accepted: 05/26/2017] [Indexed: 12/15/2022]

Hassan MA, Kim WR, Li R, Smith CI, Fried MW, Sterling RK, Ghany MG, Wahed AS, Ganova-Raeva LM, Roberts LR, Lok ASF. Characteristics of US-Born Versus Foreign-Born Americans of African Descent With Chronic Hepatitis B. Am J Epidemiol 2017;186:356-366. [PMID: 28525625 DOI: 10.1093/aje/kwx064] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Accepted: 09/14/2016] [Indexed: 12/14/2022] Open

Grant J, Agbaji O, Kramvis A, Yousif M, Auwal M, Penugonda S, Ugoagwu P, Murphy R, Hawkins C. Hepatitis B virus sequencing and liver fibrosis evaluation in HIV/HBV co-infected Nigerians. Trop Med Int Health 2017;22:744-754. [PMID: 28376292 DOI: 10.1111/tmi.12873] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]

Abstract

OBJECTIVES

Molecular characteristics of hepatitis B virus (HBV), such as genotype and genomic mutations, may contribute to liver-related morbidity and mortality. The association of these characteristics with liver fibrosis severity in sub-Saharan Africa is uncertain. We aimed to characterise molecular HBV features in human immunodeficiency virus (HIV)/HBV co-infected Nigerians and evaluate associations between these characteristics and liver fibrosis severity before and after antiretroviral therapy (ART) initiation.

METHODS

HIV/HBV co-infected Nigerians underwent liver fibrosis estimation by transient elastography (TE) prior to and 36 months after ART initiation. Basal core promoter/precore (BCP/PC) and preS1/preS2/S regions of HBV were sequenced from baseline plasma samples. We evaluated associations between HBV mutations and liver fibrosis severity by univariate and multivariable regression.

RESULTS

At baseline, 94 patients underwent TE with median liver stiffness of 6.4 (IQR 4.7-8.7) kPa. Patients were predominantly infected with HBV genotype E (45/46) and HBe-antigen negative (75/94, 79.8%). We identified BCP A1762T/G1764A in 15/35 (43%), PC G1896A in 20/35 (57%), 'a' determinant mutations in 12/45 (26.7%) and preS2 deletions in 6/16 (37.5%). PreS2 mutations were associated with advanced fibrosis in multivariable analysis. At follow-up, median liver stiffness was 5.2 (IQR 4.1-6.6) kPa. No HBV molecular characteristics were associated with lack of fibrosis regression, although HIV virologic control, body mass index (BMI) and baseline CD4+ T-cell count were associated with a decline in fibrosis stage.

CONCLUSION

Frequent BCP/PC and preS1/preS2/S mutations were found in ART-naïve HIV/HBV co-infected Nigerians. Median liver stiffness declined after initiation of ART, regardless of pre-ART HBV mutational pattern or virologic characteristics.

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Lawson-Ananissoh LM, Attia KA, Diallo D, Doffou S, Kissi YH, Bangoura D, Kouamé D, Mahassadi KA, Yao-Bathaix F, Yoman TN. Distribution et implications cliniques des génotypes du virus de l’hépatite B chez 33 porteurs chroniques du virus de l’hépatite B en Côte-d’Ivoire. ACTA ACUST UNITED AC 2017. [DOI: 10.1007/s12157-017-0726-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]

Lemoine M, Thursz MR. Battlefield against hepatitis B infection and HCC in Africa. J Hepatol 2017;66:645-654. [PMID: 27771453 DOI: 10.1016/j.jhep.2016.10.013] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Revised: 09/12/2016] [Accepted: 10/13/2016] [Indexed: 12/14/2022]

Baudi I, Iijima S, Chin'ombe N, Mtapuri-Zinyowera S, Murakami S, Isogawa M, Hachiya A, Iwatani Y, Tanaka Y. Molecular epidemiology of co-infection with hepatitis B virus and human immunodeficiency virus (HIV) among adult patients in Harare, Zimbabwe. J Med Virol 2017;89:257-266. [PMID: 27458715 DOI: 10.1002/jmv.24641] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/23/2016] [Indexed: 12/20/2022]

Thurnheer MC, Edwards R, Schulz TR, Yuen L, Littlejohn M, Revill P, Bannister E, Chu M, Tanyeri F, Wade A, Biggs BA, Sasadeusz J. Genotypic profiles of hepatitis B in African immigrants and their clinical relevance. J Med Virol 2016;89:1000-1007. [PMID: 27862013 DOI: 10.1002/jmv.24732] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Revised: 10/24/2016] [Accepted: 11/09/2016] [Indexed: 01/05/2023]

Allain JP, Opare-Sem O. Screening and diagnosis of HBV in low-income and middle-income countries. Nat Rev Gastroenterol Hepatol 2016;13:643-653. [PMID: 27625189 DOI: 10.1038/nrgastro.2016.138] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]

Godoy BA, Gomes-Gouvêa MS, Zagonel-Oliveira M, Alvarado-Mora MV, Salzano FM, Pinho JRR, Fagundes NJR. High prevalence of HBV/A1 subgenotype in native south Americans may be explained by recent economic developments in the Amazon. INFECTION GENETICS AND EVOLUTION 2016;43:354-63. [PMID: 27267305 DOI: 10.1016/j.meegid.2016.06.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Revised: 05/31/2016] [Accepted: 06/01/2016] [Indexed: 12/15/2022]

Zhou CH, Ren N. Relationship between hepatitis B virus genotypes and hepatocellular carcinoma. Shijie Huaren Xiaohua Zazhi 2016;24:1688-1694. [DOI: 10.11569/wcjd.v24.i11.1688] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open