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Faneye AO, Mustafa A, Motayo BO, Opayele AV, Akande KO. Molecular detection and genotyping of HBV from HBsAg positive patients in a tertiary hospital in Nigeria. J Immunoassay Immunochem 2024; 45:529-538. [PMID: 39222333 DOI: 10.1080/15321819.2024.2397377] [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] [Indexed: 09/04/2024]
Abstract
BACKGROUND Nigeria remains one of the countries with a high hepatitis B virus (HBV) burden in Africa. Reports have indicated the presence of mixed HBV genotypes in Nigeria; however, there is still paucity of data regarding mixed genotype infections particularly in the Southern part of the country. OBJECTIVE Our aim is to determine the HBV genotype distribution among HBsAg-positive gastroenterology patients at the University College Hospital Ibadan, Nigeria. METHOD Serum samples were screened for HBsAg by ELISA, and positive samples were genotyped by semi-nested multiplex PCR for HBV genotypes A, B, C, D, E and F. RESULTS Data generated were analyzed in R-studio. A total of 81/90 (90%) of HBsAg-positive samples were successfully genotyped, and genotype A was most prevalent with 15.7%, while genotypes B and E were the least with 1.2% each. Genotypes A/C infection was the highest among mixed infections with 40% prevalence, while genotypes A/D were the least prevalent mixed infection with 4.8%. CONCLUSION We advocate for a comprehensive genotype analysis in larger cohorts across Nigeria, to give a more comprehensive understanding of the distribution and prevalence of different HBV genotypes population wide.
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Affiliation(s)
| | - Aisha Mustafa
- Department of Virology, University of Ibadan, Ibadan, Nigeria
| | - Babatunde O Motayo
- Department of Medical Microbiology, Federal Medical Centre, Abeokuta, Nigeria
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Eleje GU, Loto OM, Usman HA, Onubogu CU, Fiebai PO, Akaba GO, Rabiu A, Mbachu II, Chibuzor MT, Chukwuanukwu RC, Joe-Ikechebelu NN, Igbodike EP, Egeonu RO, Oppah IC, Ogwaluonye UC, Nwankwo CH, Kalu SO, Chigbo CG, Ogbuagu CN, Chukwurah SN, Uzochukwu CE, Ahmed A, Jibuaku CH, Inuyomi SO, Adesoji BA, Anyang UI, Emeka EA, Igue OE, Okoro OD, Aja PO, Chidozie CP, Ibrahim HS, Aliyu FE, Ugwuoroko HC, Numan AI, Omoruyi SA, Umeononihu OS, Okoro CC, Nwaeju IK, Onwuegbuna AA, Eleje LI, Ikwuka DC, Umeh EO, Nweje SI, Ajuba IC, Ugwu AO, Ebubedike UR, Malachy DE, Okafor CG, Obiegbu NP, Ugwu EO, Yakasai IA, Ezechi OC, Ikechebelu JI. A Systematic Review and Meta-Analysis of the Prevalence of Triplex Infections (Combined Human Immunodeficiency Virus, Hepatitis B Virus, and Hepatitis C Virus) among Pregnant Women in Nigeria. Obstet Gynecol Int 2023; 2023:3551297. [PMID: 37492627 PMCID: PMC10365920 DOI: 10.1155/2023/3551297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 04/10/2023] [Accepted: 06/24/2023] [Indexed: 07/27/2023] Open
Abstract
Objective We systematically identified the prevalence of triplex infections (combined human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV)) in pregnancy. Methods To gather information on the frequency of triplex infections, we searched the databases of PubMed, CINAHL, and Google Scholar. Without regard to language, we utilized search terms that covered HIV, HBV, HCV, and pregnancy. Pregnant women with triplex infections of HIV, HBV, and HCV were included in studies that also examined the prevalence of triplex infections. Review Manager 5.4.1 was employed to conduct the meta-analysis. Critical appraisal and bias tool risk data were provided as percentages with 95% confidence intervals (95% CIs), and I2 was used as the statistical measure of heterogeneity. The checklist was created by Hoy and colleagues. The study protocol was registered on PROSPERO, under the registration number CRD42020202583. Results Eight studies involving 5314 women were included. We identified one ongoing study. Pooled prevalence of triplex infections was 0.03% (95% CI: 0.02-0.04%) according to meta-analysis. Subgroup analysis demonstrated a significantly high prevalence of 0.08% (95% CI: 0.06-0.10%; 3863 women) in HIV-positive population than 0.00% (95% CI:-0.00-0.00; 1451 women; P < 0.001) in general obstetric population. Moreover, there was a significant difference in the pooled prevalence between studies published between 2001 and 2010 and between 2011 and 2021 (0.14% (95% CI: 0.12 to 0.16 versus 0.03% (95% CI: 0.02 to 0.04%; P < 0.001))) and participants recruited in the period between 2001 and 2011 and between 2012 and 2021 (0.13% (95% CI: 0.05 to 0.21; p=0.002 versus 0.00% (95% CI: -0.00 to 0.00%; p=1.00))), respectively. Conclusion The combined prevalence of prenatal triplex infections was 0.03%, with rates notably higher among the group of pregnant women who were HIV-positive and during the recruitment period that took place before 2012. This prevalence still necessitates screening for these infections as necessary.
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Affiliation(s)
- George Uchenna Eleje
- Department of Obstetrics and Gynecology, Nnamdi Azikiwe University, Awka, Nigeria
- Department of Obstetrics and Gynecology, Nnamdi Azikiwe University Teaching Hospital, PMB 5025, Nnewi, Anambra State, Nigeria
| | - Olabisi Morebise Loto
- Department of Obstetrics and Gynecology, Obafemi Awolowo University, Ile-Ife, Nigeria
- Department of Obstetrics and Gynecology, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria
| | - Hadiza Abdullahi Usman
- Department of Obstetrics and Gynecology, University of Maiduguri, Maiduguri, Nigeria
- Department of Obstetrics and Gynecology, University of Maiduguri Teaching Hospital, Maiduguri, Nigeria
| | | | - Preye Owen Fiebai
- Department of Obstetrics and Gynecology, University of Port Harcourt, Port Harcourt, Nigeria
- Department of Obstetrics and Gynecology, University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria
| | - Godwin Otuodichinma Akaba
- Department of Obstetrics and Gynecology, University of Abuja, Abuja, Nigeria
- Department of Obstetrics and Gynecology, University of Abuja Teaching Hospital, Abuja, Nigeria
| | - Ayyuba Rabiu
- Department of Obstetrics and Gynecology, Bayero University, Kano, Nigeria
- Department of Obstetrics and Gynecology, Aminu Kano Teaching Hospital, Kano, Nigeria
| | - Ikechukwu Innocent Mbachu
- Department of Obstetrics and Gynecology, Nnamdi Azikiwe University, Awka, Nigeria
- Department of Obstetrics and Gynecology, Nnamdi Azikiwe University Teaching Hospital, PMB 5025, Nnewi, Anambra State, Nigeria
| | - Moriam Taiwo Chibuzor
- Cochrane Nigeria, Institute of Tropical Diseases Research and Prevention, University of Calabar Teaching Hospital, Calabar, Nigeria
| | | | - Ngozi Nneka Joe-Ikechebelu
- Department of Community Medicine and Primary Health Care, Faculty of Medicine, Chukwuemeka Odumegwu Ojukwu University, Amaku, Awka, Nigeria
- Department of Community Medicine and Primary Health Care, Faculty of Medicine, Chukwuemeka Odumegwu Ojukwu University Teaching Hospital, Amaku, Awka, Nigeria
| | - Emeka Philip Igbodike
- Department of Obstetrics and Gynecology, Havana Specialist Hospital, Surulere Lagos, Nigeria
| | - Richard Obinwanne Egeonu
- Department of Obstetrics and Gynecology, Nnamdi Azikiwe University Teaching Hospital, PMB 5025, Nnewi, Anambra State, Nigeria
| | - Ijeoma Chioma Oppah
- Department of Obstetrics and Gynecology, University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria
| | | | | | - Stephen Okoroafor Kalu
- HIV Care Laboratory, HIV Care Department, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria
| | | | | | - Shirley Nneka Chukwurah
- Gastroenterology Unit, Department of Medicine, Faculty of Medicine, Nnamdi Azikiwe University, Awka, Nigeria
| | | | - Aishat Ahmed
- Department of Obstetrics and Gynecology, University of Abuja Teaching Hospital, Abuja, Nigeria
| | | | | | - Bukola Abimbola Adesoji
- Department of Nursing, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria
| | - Ubong Inyang Anyang
- Department of Obstetrics and Gynecology, University of Abuja Teaching Hospital, Abuja, Nigeria
| | - Ekene Agatha Emeka
- Department of Family Medicine, Faculty of Medicine, Nnamdi Azikiwe University, Awka, Nigeria
| | - Odion Emmanuel Igue
- Department of Physiological Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Ogbonna Dennis Okoro
- Department of Parasitology & Entomology, Faculty of Veterinary Medicine, University of Maiduguri Borno State, Maiduguri, Nigeria
| | - Prince Ogbonnia Aja
- Immunology Unit, Department of Medical Laboratory Science, Nnamdi Azikiwe University, Awka, Nigeria
| | | | - Hadiza Sani Ibrahim
- Department of Obstetrics and Gynecology, Aminu Kano Teaching Hospital, Kano, Nigeria
| | - Fatima Ele Aliyu
- Department of Obstetrics and Gynecology, Aminu Kano Teaching Hospital, Kano, Nigeria
| | - Harrison Chiro Ugwuoroko
- Department of Obstetrics and Gynecology, Nnamdi Azikiwe University Teaching Hospital, PMB 5025, Nnewi, Anambra State, Nigeria
| | - Aisha Ismaila Numan
- Department of Obstetrics and Gynecology, University of Maiduguri Teaching Hospital, Maiduguri, Nigeria
| | - Solace Amechi Omoruyi
- Department of Obstetrics and Gynecology, University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria
| | - Osita Samuel Umeononihu
- Department of Obstetrics and Gynecology, Nnamdi Azikiwe University, Awka, Nigeria
- Department of Obstetrics and Gynecology, Nnamdi Azikiwe University Teaching Hospital, PMB 5025, Nnewi, Anambra State, Nigeria
| | - Chukwuemeka Chukwubuikem Okoro
- Department of Obstetrics and Gynecology, Nnamdi Azikiwe University Teaching Hospital, PMB 5025, Nnewi, Anambra State, Nigeria
| | - Ifeanyi Kingsley Nwaeju
- Department of Obstetrics and Gynecology, Nnamdi Azikiwe University Teaching Hospital, PMB 5025, Nnewi, Anambra State, Nigeria
| | | | - Lydia Ijeoma Eleje
- Measurement Evaluation and Research Unit, Department of Educational Foundations, Nnamdi Azikiwe University, Awka, Nigeria
| | | | - Eric Okechukwu Umeh
- Department of Radiology, Faculty of Medicine, Nnamdi Azikiwe University, Awka, Nigeria
| | | | - Ifeoma Clara Ajuba
- Department of Hematology, Faculty of Medicine, Nnamdi Azikiwe University, Awka, Nigeria
| | - Angela Ogechukwu Ugwu
- Department of Hematology & Immunology, College of Medicine, University of Nigeria, Ituku-Ozalla, Enugu State, Nigeria
| | | | | | - Chigozie Geoffrey Okafor
- Department of Obstetrics and Gynecology, Nnamdi Azikiwe University Teaching Hospital, PMB 5025, Nnewi, Anambra State, Nigeria
| | - Nnaedozie Paul Obiegbu
- Department of Obstetrics and Gynecology, Nnamdi Azikiwe University Teaching Hospital, PMB 5025, Nnewi, Anambra State, Nigeria
| | - Emmanuel Onyebuchi Ugwu
- Department of Obstetrics and Gynecology, College of Medicine, University of Nigeria Enugu Campus, Enugu, Nigeria
| | - Ibrahim Adamu Yakasai
- Department of Obstetrics and Gynecology, Bayero University, Kano, Nigeria
- Department of Obstetrics and Gynecology, Aminu Kano Teaching Hospital, Kano, Nigeria
| | | | - Joseph Ifeanyichukwu Ikechebelu
- Department of Obstetrics and Gynecology, Nnamdi Azikiwe University, Awka, Nigeria
- Department of Obstetrics and Gynecology, Nnamdi Azikiwe University Teaching Hospital, PMB 5025, Nnewi, Anambra State, Nigeria
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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
Abstract
Hepatitis B virus (HBV) (sub)genotypes A1, D3 and E circulate in sub-Saharan Africa, the region with one of the highest incidences of HBV-associated hepatocellular carcinoma globally. Although genotype E was identified more than 20 years ago, and is the most widespread genotype in Africa, it has not been extensively studied. The current knowledge status and gaps in its origin and evolution, natural history of infection, disease progression, response to antiviral therapy and vaccination are discussed. Genotype E is an African genotype, with unique molecular characteristics that is found mainly in Western and Central Africa and rarely outside Africa except in individuals of African descent. The low prevalence of this genotype in the African descendant populations in the New World, phylogeographic analyses, the low genetic diversity and evidence of remnants of genotype E in ancient HBV samples suggests the relatively recent re-introduction into the population. There is scarcity of information on the clinical and virological characteristics of genotype E-infected patients, disease progression and outcomes and efficacy of anti-HBV drugs. Individuals infected with genotype E have been characterised with high hepatitis B e antigen-positivity and high viral load with a lower end of treatment response to interferon-alpha. A minority of genotype E-infected participants have been included in studies in which treatment response was monitored. Of concern is that current guidelines do not consider patients infected with genotype E. Thus, there is an urgent need for further large-scale investigations into genotype E, the neglected genotype of HBV.
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Affiliation(s)
- Luicer Anne Olubayo Ingasia
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, Gauteng, South Africa
| | - Constance Wose Kinge
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, Gauteng, South Africa
- Department of Implementation Science, Right to Care, Johannesburg 0046, Gauteng, South Africa
| | - Anna Kramvis
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, Gauteng, South Africa
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Olusola BA, Faneye AO, Oluwasemowo OO, Motayo BO, Adebayo S, Oludiran-Ayoade AE, Aleru B, George UE, Oragwa AO. Profiles of mutations in hepatitis B virus surface and polymerase genes isolated from treatment-naïve Nigerians infected with genotype E. J Med Microbiol 2021; 70. [PMID: 33704041 DOI: 10.1099/jmm.0.001338] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Introduction. Hepatitis B virus (HBV) infection is the leading cause of hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). HBV genotype E (HBV/E) is the predominant genotype in West Africa and has been linked epidemiologically with chronic and occult HBV infections as well as development of HCC. Mutations in the surface and polymerase genes of HBV have been associated with occult infection, drug resistance, vaccine escape, as well as HCC.Hypothesis/Gap Statement. There is limited data on the occurrence and patterns of mutations associated with occult infection, drug resistance, vaccine escape and HCC for HBV/E.Aim. This study characterized amino acid (aa) substitutions in the major hydrophilic (MHR) and reverse transcriptase (RT) regions of the surface and polymerase genes respectively of HBV sequences from a group of Nigerians with genotype E infection. The CpG islands of the PreC/C and PreS/S regions of these sequences were also described.Methodology. HBV surface and polymerase genes were detected using PCR techniques. Occurrence of new and previously described mutations in these genes were analysed using phylogenetic techniques.Results. Overall 13 HBV isolates were each sequenced for polymerase and surface genes mutations. Thirteen and nine PreS/S and PreC/C HBV genes respectively were analysed for CpG islands. Mutations in the MHR and a-determinants region of the S protein were discovered in eleven and nine of the 13 tested isolates respectively. These mutations were concomitant with aa changes in the RT functional domains of the isolates. Mutations associated with vaccine escape, occult infection and poor HCC prognosis were identified in HBV/E isolated in this study. Furthermore, all the isolates had at least one putative nucleotide analogue resistance mutations. Drug resistance mutations had the highest association with CpG islands.Conclusion. The results of this study contribute to further understanding of HBV variability in Nigeria and the West African region. This will aid the planning of adequate HBV immunization and treatment programmes for the countries in the region.
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Affiliation(s)
- Babatunde A Olusola
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Adedayo O Faneye
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | | | - Babatunde O Motayo
- Federal Medical Center, Abeokuta, Nigeria.,Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Sopeju Adebayo
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Ayomide E Oludiran-Ayoade
- Present address: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.,Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Bisola Aleru
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Uwem E George
- Department of Biological Sciences, Redeemer's University, Ede, Osun State, Nigeria
| | - Arthur O Oragwa
- Department of Veterinary Microbiology, Faculty of Veterinary Medicine, University of Jos, Jos-Plateau State, Nigeria
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Mabunda N, Zicai AF, Ismael N, Vubil A, Mello F, Blackard JT, Lago B, Duarte V, Moraes M, Lewis L, Jani I. Molecular and serological characterization of occult hepatitis B among blood donors in Maputo, Mozambique. Mem Inst Oswaldo Cruz 2020; 115:e200006. [PMID: 32997000 PMCID: PMC7523502 DOI: 10.1590/0074-02760200006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Accepted: 08/25/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Occult hepatitis B virus (HBV) - characterized by the absence of detectable HBsAg in the presence of HBV DNA - represents a potential threat for blood safety. OBJECTIVES This study was conducted with the aim to investigate the serological and molecular characterization of occult HBV infection (OBI) among blood donors in Mozambique. METHODS 1,502 blood donors were tested for HBsAg. All HBsAg-negative individuals were tested for HBV DNA. Antibodies against HBV core, surface and HBe antigen (anti-HBc, anti-HBs, HBeAg) were measured in HBV DNA positive individuals. FINDINGS 1435 serum samples were HBsAg negative and 16 positive for HBV DNA, 14 confirmed to have OBI, corresponding to a frequency of 0.98%. Of the 14 OBI infections identified, 13/14 (92.8%) were positive for anti-HBc, 4/14 (28.5%) for anti-HBs, and no samples were reactive for HBeAg. Of the 14 OBI cases, nine samples (64.2%) were sequenced for the S/P region. Eight samples (88.9%) belonged to genotype A1 and one (11.1%) to genotype E. One escape mutation (T123A) associated with OBI and various amino acid substitutions for genotype A1 and E were observed. MAIN CONCLUSIONS Our results show the importance of using nucleic acid amplification test to detect occult hepatitis B infection in blood donors in Mozambique.
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Affiliation(s)
- Nédio Mabunda
- Instituto Nacional de Saúde, Maputo, Mozambique.,Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Hanseníase, Rio de Janeiro, RJ, Brasil
| | | | | | | | - Francisco Mello
- Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Hepatites Virais, Rio de Janeiro, RJ, Brasil
| | - Jason T Blackard
- University of Cincinnati College of Medicine, Division of Digestive Diseases, United States of America
| | - Barbara Lago
- Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Hepatites Virais, Rio de Janeiro, RJ, Brasil
| | - Vanessa Duarte
- Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Hepatites Virais, Rio de Janeiro, RJ, Brasil
| | - Milton Moraes
- Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Hanseníase, Rio de Janeiro, RJ, Brasil
| | - Lia Lewis
- Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Hepatites Virais, Rio de Janeiro, RJ, Brasil
| | - Ilesh Jani
- Instituto Nacional de Saúde, Maputo, Mozambique
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Pennap GR, Mohammed HI, Oti VB, Adoga MP. Genotype distribution of hepatitis B virus in a subset of infected young people in Central Nigeria. SCIENTIFIC AFRICAN 2019. [DOI: 10.1016/j.sciaf.2019.e00122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
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Matlou MK, Gaelejwe LR, Musyoki AM, Rakgole JN, Selabe SG, Amponsah-Dacosta E. A novel hepatitis B virus recombinant genotype D4/E identified in a South African population. Heliyon 2019; 5:e01477. [PMID: 31008405 PMCID: PMC6453802 DOI: 10.1016/j.heliyon.2019.e01477] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 03/08/2019] [Accepted: 04/01/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Genetic diversity is a characteristic trait of the hepatitis B virus (HBV) and has been associated with different clinical outcomes. In South Africa, HBV infection is a major public health concern. Most HBV infections are caused by genotype A strains. However rare cases of infection with HBV genotype D have been reported. The purpose of this study was to investigate the molecular characteristics of a rare HBV subgenotype D4 isolate. METHODS The full-length genome of isolate ZADGM6964 was amplified in a one-step polymerase chain reaction. The amplified product was purified and cloned into a pGEM®-T Easy Vector System to investigate the genetic diversity of the viral quasi-populations. The primary isolate and clones were then directly sequenced and analysed using an array of bioinformatics software. RESULTS Phylogenetic analysis showed that the primary isolate and cloned sequences formed a monophyletic cluster away from subgenotype D4 reference strains. Further recombination analysis revealed that isolate ZADGM6964 was in fact a D4/E recombinant strain with breakpoints identified within the X and overlapping pre-Core/Core open reading frames with a >70% bootstrap confidence level. The recombinant genotype D4/E was found to be unique from other D/E strains archived in the genetic database, GenBank. CONCLUSION This study represents the first ever report on the isolation and molecular characterization of an HBV D4/E recombinant strain in South Africa. The findings provide evidence of further HBV genetic diversity in South Africa than has been previously reported.
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Affiliation(s)
- Mmatsatsi K. Matlou
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
| | - Lucinda R. Gaelejwe
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
| | - Andrew M. Musyoki
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
- Department of Microbiological Pathology, Sefako Makgatho Health Sciences University, Pretoria, South Africa
| | - J. Nare Rakgole
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
| | - Selokela G. Selabe
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
| | - Edina Amponsah-Dacosta
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
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Torres MC, Civetta E, D'amico C, Barbini L. Hepatitis B virus in Mar del Plata, Argentina: Genomic characterization and evolutionary analysis of subgenotype F1b. J Med Virol 2019; 91:791-802. [PMID: 30570771 DOI: 10.1002/jmv.25383] [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: 07/13/2018] [Accepted: 12/14/2018] [Indexed: 11/07/2022]
Abstract
The aim is to describe the molecular epidemiology and perform a genomic characterization of hepatitis B virus (HBV) circulating in Mar del Plata and to identify the origin and diversification patterns of the most prevalent genotype. The S gene and the region encompassing the X gene, basal core promoter (BCP), and precore (preC) was analyzed in 56 samples. They were genotyped as: 80% F1b, 9% A2, 7% D3, and 2% D1. A recombinant F4/D2 genome was detected. The double substitution G1764A/A1762T at the BCP (reduced HBeAg expression) was found in 20% F1b, 2% A2, 2% D1, and 2% D3 samples. A unique D3 presented the G1896A substitution at the preC (HBeAg negative phenotype). A 13% of the samples showed mutations at the HBsAg "a" immunodeterminant (escape from neutralizing antibodies). Mutations at the polymerase (antiviral resistance) were found in 52% of the samples. Coalescent analysis of subgenotype F1b, the most prevalent in the city, showed that viral diversification in Mar del Plata started by year 2000. F1b was the most prevalent genotype detected, being a characteristic of actual HBV infections in Mar del Plata. Local HBV exhibit clinically relevant mutations, but a minority of them was shown to be associated to potential vaccination escape or antiviral resistance. Nevertheless, further studies are needed to determine whether any of these mutants could pose a threat to prevention, diagnosis, or treatment.
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Affiliation(s)
| | - Elida Civetta
- Unidad de Hepatología y Alcoholismo, HIGA Dr. O. Alende, Mar del Plata, Argentina
| | - Claudia D'amico
- Centro de Especialidades Médicas Ambulatorias, Unidad de Hepatología, Mar del Plata, Argentina
| | - Luciana Barbini
- Departamento de Química, FCEyN, UNMdP, Buenos Aires, Argentina
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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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Affiliation(s)
- Jennifer Grant
- Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Oche Agbaji
- Department of Medicine, University of Jos and Jos University Teaching Hospital, Jos, Nigeria
| | - Anna Kramvis
- School of Clinical Medicine, Faculty of Health Sciences, Hepatitis Virus Diversity Research Unit, University of the Witwatersrand, Johannesburg, South Africa
| | - Mukhlid Yousif
- School of Clinical Medicine, Faculty of Health Sciences, Hepatitis Virus Diversity Research Unit, University of the Witwatersrand, Johannesburg, South Africa
| | - Mu'azu Auwal
- HIV Care and Treatment Center, Jos University Teaching Hospital, Jos, Nigeria
| | - Sudhir Penugonda
- Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Placid Ugoagwu
- HIV Care and Treatment Center, Jos University Teaching Hospital, Jos, Nigeria
| | - Robert Murphy
- Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Claudia Hawkins
- Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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10
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Olusola BA, Gometi EA, Ogunsemowo O, Olaleye DO, Odaibo GN. High rate of Hepatitis B virus infection among hairdressers in Ibadan, Nigeria. J Immunoassay Immunochem 2017; 38:322-332. [PMID: 28318369 DOI: 10.1080/15321819.2016.1260585] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Hepatitis B virus (HBV) infection is a major public health problem for over two billion people infected globally. Occupationally exposed persons are at high risk of HBV infection and, apart from medical personnel, there is dearth of information concerning the prevalence and awareness of HBV among this population in Nigeria. This study was designed to determine the levels of HBV awareness and prevalence of HBV infection among hairdressers in Ibadan, Nigeria. Hairdressers and teachers (unmatched controls) in four local government areas in Ibadan were tested for HBV infection using ELISA technique. Dried blood spot (DBS) samples were collected from 171 participants. DBS elutes from the samples were tested for HBV surface antigen (HBsAg). The rate of HBV infection was higher (p = 0.005) among the hairdressers (13.0%) than teachers (4.8%). However, teachers were better informed about HBV (38%) compared to hairdressers (13%; p = 0.0001). Differences in HBV awareness and occupation type were found to be significant (P = 0.001). Hairdressers are at high risk of HBV infection and may constitute a major source of HBV spread among urban dwellers, especially in areas where awareness is low. Routine HBV screening and appropriate interventions for hairdressers are recommended to interrupt HBV transmission.
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Affiliation(s)
- B A Olusola
- a Department of Virology, College of Medicine , University of Ibadan , Ibadan , Nigeria
| | - E A Gometi
- a Department of Virology, College of Medicine , University of Ibadan , Ibadan , Nigeria
| | - O Ogunsemowo
- a Department of Virology, College of Medicine , University of Ibadan , Ibadan , Nigeria
| | - D O Olaleye
- a Department of Virology, College of Medicine , University of Ibadan , Ibadan , Nigeria
| | - G N Odaibo
- a Department of Virology, College of Medicine , University of Ibadan , Ibadan , Nigeria
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11
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Velay A, Jeulin H, Eschlimann M, Malvé B, Goehringer F, Bensenane M, Frippiat JP, Abraham P, Ismail AM, Murray JM, Combet C, Zoulim F, Bronowicki JP, Schvoerer E. Characterization of hepatitis B virus surface antigen variability and impact on HBs antigen clearance under nucleos(t)ide analogue therapy. J Viral Hepat 2016; 23:387-98. [PMID: 26742490 DOI: 10.1111/jvh.12498] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Accepted: 11/01/2015] [Indexed: 12/15/2022]
Abstract
For hepatitis B virus (HBV)-related chronic infection under treatment by nucleos(t)ide analogues (NUCs), HBsAg clearance is the ultimate therapeutic goal but very infrequent. We investigated how HBV envelope protein variability could lead to differential HBsAg clearance on NUCs. For 12 HBV genotype D patients receiving NUCs, six resolvers (HBsAg clearance) were compared to six matched nonresolvers (HBsAg persistence). PreS/S amino acid (aa) sequences were analysed with bioinformatics to predict HBV envelope antigenicity and aa covariance. To enrich our analyses on very rare resolvers, these were compared with other HBV genotype D strains in three characterized clinical cohorts including common chronically infected patients. The sT125M+sP127T combination was observed in four nonresolvers of six, corroborated by aa covariance analysis, associated with a lower predicted antigenicity than sT125T+sP127P. Concordant features within this HBV key functional domain, at positions 125 and 127, were reported from two of the three comparative cohorts. In our hands, a lower ELISA reactivity of HBV-vaccinated mice sera was observed against the sT125M mutant. In the S gene, 56 aa changes in minor variants were detected in non-resolvers, mainly in the major hydrophilic region, vs 28 aa changes in resolvers. Molecular features in patients showing HBsAg persistence on NUCs argue in favour of a different aa pattern in the HBV S gene compared to those showing HBsAg clearance. In nonresolvers, a decrease in HBs 'a' determinant antigenicity and more frequent mutations in the S gene suggest a role for the HBV envelope characteristics in HBsAg persistence.
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Affiliation(s)
- A Velay
- EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France
| | - H Jeulin
- EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.,Laboratoire de Virologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France
| | - M Eschlimann
- EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France
| | - B Malvé
- Laboratoire de Virologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France
| | - F Goehringer
- Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France
| | - M Bensenane
- Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France
| | - J-P Frippiat
- EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France
| | - P Abraham
- Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India
| | - A M Ismail
- Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India
| | - J M Murray
- School of Mathematics and Statistics, UNSW Australia, Sydney, NSW, Australia
| | - C Combet
- Unité Inserm UI1052, Université de Lyon, Lyon, France
| | - F Zoulim
- Unité Inserm UI1052, Université de Lyon, Lyon, France
| | - J-P Bronowicki
- Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France
| | - E Schvoerer
- EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.,Laboratoire de Virologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France
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12
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Tufon KA, Meriki HD, Anong DN, Mbunkah HA, Nkuo-Akenji T. Genetic diversity, viraemic and aminotransferases levels in chronic infected hepatitis B patients from Cameroon. BMC Res Notes 2016; 9:117. [PMID: 26899506 PMCID: PMC4762165 DOI: 10.1186/s13104-016-1916-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2015] [Accepted: 02/04/2016] [Indexed: 01/05/2023] Open
Abstract
Background HBV infection annually accounts for 1 million deaths worldwide as a result of cirrhosis, liver failure, and hepatocellular carcinoma. In addition to varying responses to antiviral therapy, HBV genotypes have also been shown to be associated with different pattern of disease progression. Despite a high HBV prevalence of >8 %, very few studies have been carried out in Cameroon to determine the genotype distribution across the country. The aim of this study was to determine the prevalent genotypes, level of viraemia and correlate these parameters with liver enzymes known to be the most affordable and widely used biomarkers for monitoring disease progression in Cameroon. Methods This was a hospital-community based study in which 81 participants who had been previously diagnosed of HBV were recruited and screened for HIV, HCV (for exclusion) and HBsAg for confirmation. Fifty known negative cases for HIV, HBV and HCV were tested and recruited to be used as healthy controls. Viral load and genotyping was performed only for HBV-mono infected cases using the Abbott RealTime HBV automated m2000 system and INNO-LiPA HBV Genotyping assay respectively. Liver enzymes were measured by spectrophotometry on both hepatitis B positive and healthy control cases. Results
The mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly higher (p < 0.001) in HBV infected patients than “healthy controls”. Of the 81 HBV infected cases viral load was detected in 76 (93.8 %) with mean viral load of 120,807 IU/ml ± 440,159 SD. Mean viral load was significantly different in patients with abnormal AST and ALT when compared with patients who had normal ALT and AST. The identified genotypes in order of prevalence were A (47.4 %), E (39.5 %), C/E (3.9 %) A/C (2.6 %), A/E (2.6 %), B (1.3 %), A/B (1.3 %) and B/C (1.3 %). Conclusion Genotype E was significantly associated with higher mean viral load and mean AST levels. However, aminotransferase levels may not be a good marker for HBV disease progression as some patients could have normal levels but still present with very high viral loads and therefore, remain active HBV infection with possible high transmission.
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Affiliation(s)
- Kukwah Anthony Tufon
- Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon. .,Microbiology Unit, Buea Regional Hospital, Buea, Southwest Region, Cameroon.
| | - Henry Dilonga Meriki
- Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon. .,Microbiology Unit, Buea Regional Hospital, Buea, Southwest Region, Cameroon. .,BioCollections Worldwide Inc., Miami, FL, USA.
| | - Damian Nota Anong
- Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon.
| | - Herbert Afegenwi Mbunkah
- Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon.
| | - Theresa Nkuo-Akenji
- Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon. .,Clinical Diagnostic Laboratory, Faculty of Science, University of Buea, P.O. Box 63, Buea, Cameroon. .,Internal Control and Evaluation, University of Buea, Buea, Cameroon.
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13
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Faleye TOC, Adewumi OM, Ifeorah IM, Akere A, Bakarey AS, Omoruyi EC, Oketunde K, Awonusi OB, Ajayi MR, Adeniji JA. Detection and circulation of hepatitis B virus immune escape mutants among asymptomatic community dwellers in Ibadan, southwestern Nigeria. Int J Infect Dis 2015; 39:102-9. [PMID: 26283552 DOI: 10.1016/j.ijid.2015.08.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2015] [Revised: 07/25/2015] [Accepted: 08/09/2015] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND In 2012, the first Nigerian Hepatitis B Virus (HBV) immune escape mutant (IEM) case was detected in a pregnant woman in southwestern Nigeria. Consequently, this study was designed to investigate the presence and possible circulation of IEMs amongst asymptomatic community dwellers in southwestern Nigeria. METHODS Blood specimens collected from 438 asymptomatic community dwellers were screened for HBsAg using ELISA technique. Subsequently, the S-gene was amplified in HBsAg positive samples by a nested PCR protocol, and amplicons sequenced. Isolates were then subtyped by amino acid residues at positions 122, 127, 134 and 160, and genotyped by phylogenetic analysis. RESULTS Of the 31 (7.08%) samples positive for HBsAg, the ∼ 408 bp Sgene fragment was successfully amplified and sequenced in 27. Samples obtained from 4 patients could not be amplified due to low titres. Sequence data from only 15 of the isolates could be analysed further as eight of the remaining 12 had multiple peaks while the rest three showed no similarity to any HBV gene when subjected to BLAST analysis. Thirteen of the 15 isolates were identified as genotype E. Eleven of which were subtyped as ayw4 while the remaining two could not be subtyped due to sR122Q/P substitutions. The last two isolates that could not be genotyped and subtyped had other mutations in the "a" determinant associated with IEMs. CONCLUSIONS This study confirmed presence and circulation of HBV IEM in Nigeria, the country's inclusion in the genotype E crescent, and the value of phylogenetic analysis in HBV identification.
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Affiliation(s)
- Temitope Oluwasegun Cephas Faleye
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria; Department of Microbiology, Faculty of Science, Ekiti State University, Ado Ekiti, Ekiti State, Nigeria.
| | - Olubusuyi Moses Adewumi
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria.
| | - Ijeoma Maryjoy Ifeorah
- Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria.
| | - Adegboyega Akere
- Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria.
| | - Adeleye Solomon Bakarey
- Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria.
| | - Ewean Chukwuma Omoruyi
- Institute of Child Health, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria.
| | - Kemi Oketunde
- Department of Science Laboratory Technology, Faculty of Science, Ekiti State University, Ado Ekiti, Ekiti, State, Nigeria.
| | - Oluwajumoke Bosede Awonusi
- Department of Science Laboratory Technology, Faculty of Science, Ekiti State University, Ado Ekiti, Ekiti, State, Nigeria.
| | - Modupe Racheal Ajayi
- Department of Microbiology, Faculty of Science, Ekiti State University, Ado Ekiti, Ekiti State, Nigeria.
| | - Johnson Adekunle Adeniji
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria; WHO National Polio Laboratories, University of Ibadan, Ibadan, Oyo State, Nigeria.
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Molecular characterisation of hepatitis B virus in HIV-1 subtype C infected patients in Botswana. BMC Infect Dis 2015; 15:335. [PMID: 26268355 PMCID: PMC4535680 DOI: 10.1186/s12879-015-1096-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2015] [Accepted: 08/06/2015] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) is a major global health problem especially in sub-Saharan Africa and in East Asia. Ten hepatitis B virus genotypes have been described that differ by geographic distribution, disease progression, and response to treatment. Escape mutations within the surface open reading frame (ORF) affect HBV antigenicity leading to failures in diagnosis, vaccine and hepatitis B immunoglobulin therapy. However, the molecular characteristics of HBV in Botswana, a highly endemic country, are unknown. We describe the molecular characteristics of HBV and prevalence of escape mutants among HIV/HBV coinfected individuals Botswana. METHODS DNA was extracted from archived plasma samples from 81 HIV/HBV co-infected participants from various clinical studies at the Botswana Harvard AIDS Institute Partnership. A 415 base pair (bp) fragment of the polymerase gene was amplified by semi-nested PCR. In a subset of samples, a 2100 bp fragment was amplified. The PCR product was genotyped using Big Dye sequencing chemistry and the sequences were analysed for genotypes and mutations. RESULTS Of the 81 samples included, 70 (86 %) samples were successfully genotyped. Genotype A was found in 56 (80 %) participants, D in 13 (18.6 %), and 1 (1.4 %) was genotype E. Escape mutations previously linked with failure of diagnosis or escaping active vaccination and passive immunoglobulin therapy were detected in 12 (17.1 %) participants at positions 100, 119, 122, 123, 124, 126, 129, 130, 133, 134 and 140 of the S ORF. Genotypes and escape mutations were not significantly associated with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and AST platelet ratio index (APRI). CONCLUSION Genotypes A, D and E were found in this cohort of HIV coinfected patients in Botswana, consistent with the findings from the sub-Saharan Africa region. Some escape mutations which have previously been associated with diagnosis failure, escaping vaccine and immunoglobulin therapy were also observed and are important in guiding future policies related to vaccine implementation, therapeutic guidelines, and diagnostic guidelines. They are also important for identifying patients who are at an increased risk of disease progression and to choose optimal therapy. Future research should focus on determining the clinical significance of the different HBV genotypes and mutations found in this population.
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Mello FMMAD, Kuniyoshi ASO, Lopes AF, Gomes-Gouvêa MS, Bertolini DA. Hepatitis B virus genotypes and mutations in the basal core promoter and pre-core/core in chronically infected patients in southern Brazil: a cross-sectional study of HBV genotypes and mutations in chronic carriers. Rev Soc Bras Med Trop 2015; 47:701-8. [PMID: 25626648 DOI: 10.1590/0037-8682-0158-2014] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2014] [Accepted: 11/11/2014] [Indexed: 01/04/2023] Open
Abstract
INTRODUCTION In Brazil, little data exist regarding the distribution of genotypes in relation to basal core promoter (BCP) and precore/core mutations among chronic hepatitis B virus (HBV) carriers from different regions of the country. The aim of this study was to identify HBV genotypes and the frequency of mutations at the BCP and precore/core region among the prevalent genotypes in chronic carriers from southern Brazil. METHODS Nested-polymerase chain reaction (nested-PCR) products amplified from the S-polymerase gene, BCP and precore/core region from 54 samples were sequenced and analyzed. RESULTS Phylogenetic analysis of the S-polymerase gene sequences showed that 66.7% (36/54) of the patients were infected with genotype D (D1, D2, D3), 25.9% (14/54) with genotype A (A1, A2), 5.6% (3/54) with subgenotype C2, and 2% (1/54) with genotype E. A comparison of virological characteristics showed significant differences between genotypes A, C and D. The comparison between HBeAg status and the G1896A stop codon mutation in patients with genotype D revealed a relationship between HBV G1896A precore mutants and genotype D and hepatitis B e antigen (HBeAg) seroconversion. Genotype D had a higher prevalence of the G1896A mutation and the presence of a thymine at position 1858. Genotype A was associated with a higher prevalence of the G1862T mutation and the presence of a cytosine at position 1858. CONCLUSIONS HBV genotype D (D3) is predominant in HBV chronic carriers from southern Brazil. The presence of mutations in the BCP and precore/core region was correlated with the HBV genotype and HBeAg negative status.
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Affiliation(s)
| | | | - André Fanhani Lopes
- Laboratório de Virologia Clínica, Departamento de Análises Clínicas e Biomedicina, Universidade Estadual de Maringá, Maringá, PR
| | - Michele Soares Gomes-Gouvêa
- Laboratório de Gastroenterologia Tropical do Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Dennis Armando Bertolini
- Laboratório de Virologia Clínica, Departamento de Análises Clínicas e Biomedicina, Universidade Estadual de Maringá, Maringá, PR
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Occult Hepatitis B Virus Infection in Nigerian Blood Donors and Hepatitis B Virus Transmission Risks. PLoS One 2015; 10:e0131912. [PMID: 26148052 PMCID: PMC4492924 DOI: 10.1371/journal.pone.0131912] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Accepted: 06/08/2015] [Indexed: 02/06/2023] Open
Abstract
Background Occult hepatitis B virus infection (OBI) characterized by the absence of detectable HBsAg remains a potential threat in blood safety. We investigated the actual prevalence, viral factors and genotype of OBI infections in Nigerian blood donors. Methods Serum collected from two blood banks were reconfirmed as HBsAg seronegative by ELISA. Forty HBsAg positive samples were employed as controls. HBV-DNA was amplified from all donors and viral loads were determined using quantitative real-time PCR. Antibodies to the HBV core, surface and HBe antigen (anti-HBc,anti-HBs,HBeAg) were measured. The PreS/S and PreC/C regions of the HBV genome were sequenced. Results Of the 429 blood donors, 72(17%) were confirmed as OBI by DNA detection in different reference labs and excluded the concern of possible contamination. Of the 72 OBI samples, 48(67%) were positive for anti-HBc, 25(35%) positive for anti-HBs, and 2(3%) positive for HBeAg. Of the 72 OBI samples, 31(43%) were seropositive for either anti-HBc, anti-HBs or HBeAg, 21 (30%) positive for both anti-HBc and anti-HBs,one positive for both anti-HBc and HBeAg. None of the OBI samples were positive for all three serological markers. The viral load was <50copies/ml in the OBI samples and genotype E was predominant. The L217R polymorphism in the reverse transcriptase domain of the HBV polymerase gene was observed significantly higher in OBI compared with HBsAg positive individuals (P<0.0001). Conclusion High incidence of OBI is relevant in high endemic areas worldwide and is a general burden in blood safety. This study signifies the high prevalence of OBI and proposes blood donor samples in Nigeria should be pre-tested for OBI by nucleic acid testing (NAT) and/or anti-HBc prior to transfusion to minimize the HBV infection risk.
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Faleye TOC, Adewumi MO, Ifeorah IM, Omoruyi EC, Bakarey SA, Akere A, Awokunle F, Ajibola HO, Makanjuola DO, Adeniji JA. Detection of hepatitis B virus isolates with mutations associated with immune escape mutants among pregnant women in Ibadan, southwestern Nigeria. SPRINGERPLUS 2015; 4:43. [PMID: 25674500 PMCID: PMC4320141 DOI: 10.1186/s40064-015-0813-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/30/2014] [Accepted: 01/12/2015] [Indexed: 12/14/2022]
Abstract
Perinatal transmission of hepatitis B virus (HBV) and its associated immune escape mutants (IEMs), is the major vehicle through which a population of chronically infected people who serve as infectious HBV reservoirs is maintained in communities. Therefore, to assess the risk of perinatal transmission, 272 pregnant women attending ante-natal clinics in Ibadan metropolis, southwestern, Nigeria, were screened for HBsAg using ELISA technique. Samples positive for HBsAg were subjected to HBV DNA detection by PCR amplification of the S-gene and amplicon sequencing. Isolates were genotyped and subtyped using a combination of molecular techniques. Fifteen (5.5%) of the pregnant women were positive for HBsAg of which HBV DNA was detected in seven. Five of the isolates were typed as genotype E subtype ayw4 using amino acid residues at positions 122, 127, 134 and 160. Another could only be typed as genotype E subtype ayw4 by further phylogenetic analysis. The remaining one isolate did not belong to any of genotypes A – H. Three of the HBV isolates including the untypable, had mutations in the ‘a’ determinant associated with IEMs. This study confirms the endemicity of HBV, the risk of perinatal transmission and the circulation of genotype E subtype ayw4 in Nigeria. It further demonstrates the presence of IEMs in Nigeria.
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Affiliation(s)
- Temitope Oluwasegun Cephas Faleye
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Oyo State Nigeria ; Department of Microbiology, Faculty of Science, Ekiti State University, Ado Ekiti, Ekiti State Nigeria
| | - Moses Olubusuyi Adewumi
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Oyo State Nigeria
| | - Ijeoma Maryjoy Ifeorah
- Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Oyo State Nigeria
| | - Ewean Chukwuma Omoruyi
- Institute of Child Health, College of Medicine, University of Ibadan, Ibadan, Oyo State Nigeria
| | - Solomon Adeleye Bakarey
- Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Oyo State Nigeria
| | - Adegboyega Akere
- Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Oyo State Nigeria
| | - Funmilola Awokunle
- Department of Science Laboratory Technology, Faculty of Science, Ekiti State University, Ado Ekiti, Ekiti State Nigeria
| | - Hannah Opeyemi Ajibola
- Department of Microbiology, Faculty of Science, Ekiti State University, Ado Ekiti, Ekiti State Nigeria
| | - Deborah Oluwaseyi Makanjuola
- Department of Science Laboratory Technology, Faculty of Science, Ekiti State University, Ado Ekiti, Ekiti State Nigeria
| | - Johnson Adekunle Adeniji
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Oyo State Nigeria ; WHO National Polio Laboratory, University of Ibadan, Ibadan, Oyo State Nigeria
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Pourkarim MR, Amini-Bavil-Olyaee S, Kurbanov F, Van Ranst M, Tacke F. Molecular identification of hepatitis B virus genotypes/subgenotypes: revised classification hurdles and updated resolutions. World J Gastroenterol 2014; 20:7152-68. [PMID: 24966586 PMCID: PMC4064061 DOI: 10.3748/wjg.v20.i23.7152] [Citation(s) in RCA: 146] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2013] [Revised: 11/28/2013] [Accepted: 01/02/2014] [Indexed: 02/06/2023] Open
Abstract
The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term "recombino-subgenotype". Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term "immigro-subgenotype" to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.
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Analysis of complete nucleotide sequences of Angolan hepatitis B virus isolates reveals the existence of a separate lineage within genotype E. PLoS One 2014; 9:e92223. [PMID: 24632784 PMCID: PMC3954871 DOI: 10.1371/journal.pone.0092223] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2013] [Accepted: 02/19/2014] [Indexed: 02/07/2023] Open
Abstract
Hepatitis B virus genotype E (HBV/E) is highly prevalent in Western Africa. In this work, 30 HBV/E isolates from HBsAg positive Angolans (staff and visitors of a private hospital in Luanda) were genetically characterized: 16 of them were completely sequenced and the pre-S/S sequences of the remaining 14 were determined. A high proportion (12/30, 40%) of subjects tested positive for both HBsAg and anti-HBs markers. Deduced amino acid sequences revealed the existence of specific substitutions and deletions in the B- and T-cell epitopes of the surface antigen (pre-S1- and pre-S2 regions) of the virus isolates derived from 8/12 individuals with concurrent HBsAg/anti-HBs. Phylogenetic analysis performed with 231 HBV/E full-length sequences, including 16 from this study, showed that all isolates from Angola, Namibia and the Democratic Republic of Congo (n = 28) clustered in a separate lineage, divergent from the HBV/E isolates from nine other African countries, namely Cameroon, Central African Republic, Côte d'Ivoire, Ghana, Guinea, Madagascar, Niger, Nigeria and Sudan, with a Bayesian posterior probability of 1. Five specific mutations, namely small S protein T57I, polymerase Q177H, G245W and M612L, and X protein V30L, were observed in 79-96% of the isolates of the separate lineage, compared to a frequency of 0–12% among the other HBV/E African isolates.
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Forbi JC, Ben-Ayed Y, Xia GL, Vaughan G, Drobeniuc J, Switzer WM, Khudyakov YE. Disparate distribution of hepatitis B virus genotypes in four sub-Saharan African countries. J Clin Virol 2013; 58:59-66. [PMID: 23871163 PMCID: PMC4591023 DOI: 10.1016/j.jcv.2013.06.028] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2013] [Revised: 05/23/2013] [Accepted: 06/21/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV) places a substantial health burden on Africa. Here, we investigated genetic diversity of HBV variants circulating in 4 countries of sub-Saharan Africa using archived samples. In total, 1492 plasma samples were tested from HIV-infected individuals and pregnant women, among which 143 (9.6%) were PCR-positive for HBV DNA (Côte d'Ivoire, 70/608 [11.5%]; Ghana, 13/444 [2.9%]; Cameroon, 33/303 [10.9%]; and Uganda, 27/137 [19.7%]). STUDY DESIGN/RESULTS Phylogenetic analysis of the S-gene sequences identified HBV genotypes E (HBV/E, n=96) and A (HBV/A, n=47) distributed as follows: 87% of HBV/E and 13% of HBV/A in Côte d'Ivoire; 100% of HBV/E in Ghana; 67% of HBV/E and 33% of HBV/A in Cameroon; and 100% of HBV/A in Uganda. The average and maximal nucleotide distances among HBV/E sequences were 1.9% and 6.4%, respectively, suggesting a greater genetic diversity for this genotype than previously reported (p<0.001). HBV/A strains were classified into subgenotypes HBV/A1, HBV/A2 and HBV/A3. In Uganda, 93% of HBV/A strains belonged to HBV/A1 whereas HBV/A3 was the only subgenotype of HBV/A found in Cameroon. In Côte d'Ivoire, HBV/A strains were classified as HBV/A1 (11.1%), HBV/A2 (33.3%) and HBV/A3 (55.6%). Phylogeographic analysis of the sequences available from Africa supported earlier suggestions on the origin of HBV/A1, HBV/A2 and HBV/A3 in East, South and West/Central Africa, respectively. Using predicted amino acid sequences, hepatitis B surface antigen (HBsAg) was classified into serotype ayw4 in 93% of HBV/E strains and adw2 in 68% of HBV/A strains. Also, 7.7% of the sequences carried substitutions in HBsAg associated with immune escape. CONCLUSIONS The observations of pan-African and global dissemination of HBV/A1 and HBV/A2, and the circulation of HBV/E and HBV/A3 almost exclusively in West and Central Africa suggest a more recent increase in prevalence in Africa of HBV/E and HBV/A3 compared to HBV/A1 and HBV/A2. The broad genetic heterogeneity of HBsAg detected here may impact the efficacy of prevention and control efforts in sub-Saharan Africa.
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Affiliation(s)
- Joseph C Forbi
- Molecular Epidemiology and Bioinformatics Laboratory, Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Atlanta, GA 30333, USA.
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21
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Martinez AA, Zaldivar Y, Hong CC, Alvarado-Mora MV, Smith R, Ortiz AY, Pinho JRR, Cristina J, Pascale JM. Molecular characterisation of hepatitis B virus in the resident Chinese population in Panama City. Mem Inst Oswaldo Cruz 2013; 108:541-7. [PMID: 23903967 PMCID: PMC3970604 DOI: 10.1590/s0074-02762013000500002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2013] [Accepted: 04/26/2013] [Indexed: 02/06/2023] Open
Abstract
Despite the effectiveness of current hepatitis B virus (HBV) vaccines, it is estimated that 350 million individuals suffer from chronic HBV infection and more than 50% of these affected individuals live on the Asian continent. Panama is a country with a great diversity of foreign groups; the Chinese community is a large example of this phenomenon. There is an urgent need to perform studies that evaluate the prevalence and the genetic diversity of HBV in this community. This study aimed to evaluate the prevalence of HBV and its genotypes and mutant variants in the Chinese population residing in Panama. In total, 320 subjects were enrolled in the study. Forty-two subjects (13.1%) were positive for HBsAg and HBV-DNA from 18 subjects revealed the presence of genotypes B2 and C1. Secondary mutations associated with drug resistance at positions rtV207L and rtN239T of the reverse transcriptase gene were identified. Additionally, the mutation pair A1762T/G1764A was found in three samples and the mutation G1896A was detected in an HBeAg-negative subject. In conclusion, to our knowledge, this is the first study to report high HBV prevalence rates in resident ethnic Chinese in Central America and the presence of genotypes B2 and C1 in this region.
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Affiliation(s)
- Alexander Augusto Martinez
- Gorgas Memorial Institute for Health Studies, Panama, Panama
- Department of Biotechnology, Acharya Nagarjuna University, Guntur,
India
- Instituto de Investigaciones Científicas y Servicios de Alta
Tecnología-AIP, Ciudad del Saber, Clayton, Panama
| | | | - Chen Ch Hong
- Internal Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Monica Viviana Alvarado-Mora
- Laboratório de Gastroenterologia e Hepatologia Tropical,
Departamento de Gastroenterologia, Instituto de Medicina Tropical, Faculdade de
Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
| | - Rebecca Smith
- Gorgas Memorial Institute for Health Studies, Panama, Panama
| | - Alma Y Ortiz
- Gorgas Memorial Institute for Health Studies, Panama, Panama
| | - João Renato Rebello Pinho
- Laboratório de Gastroenterologia e Hepatologia Tropical,
Departamento de Gastroenterologia, Instituto de Medicina Tropical, Faculdade de
Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
| | - Juan Cristina
- Laboratorio de Virología Molecular, Centro de Investigaciones
Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
| | - Juan Miguel Pascale
- Gorgas Memorial Institute for Health Studies, Panama, Panama
- School of Medicine, University of Panama, Panama, Panama
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Odaibo GN, Ola SO, Olaleye OD. Hepatitis B virus DNA in patients with HBsAg in south western Nigeria. J Med Virol 2012; 85:214-8. [PMID: 23161583 DOI: 10.1002/jmv.23418] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/20/2012] [Indexed: 11/06/2022]
Abstract
There are about 400 million people with chronic hepatitis B virus (HBV) infection worldwide with a potential of adverse sequelae including hepatocellular carcinoma. Recent data have shown that the level of HBV DNA in serum or plasma of an infected person probably reflects more accurately the replicative activity of the virus and therefore may serve as a better maker for management of the infection. This study was designed to determine the rate of detection of HBV DNA in blood samples of patients with HBsAg positive in Nigeria in comparison with the HBe and anti-HBe used widely as serological markers of infectivity. Plasma samples from 105 patients with HBsAg positive were tested for the presence of HBeAg and anti-HBe using a commercial enzyme-linked immunosorbent assay while plasma HBV DNA was quantified using the COBAS Amplicor HBV Monitor assay. Of the 105 HBsAg samples, 17 (16.2%) and 85 (81%) were positive for HBeAg and anti-HBe, respectively, while 8 (7.6%) were negative for both HBeAg and anti-HBe. HBV DNA was detected in 86 (81.9%) of the samples, out of which 15 (18.1%) and 67 (80.7%) were positive for HBeAg and anti-HBe, respectively. HBV DNA was detected in 78.4% of the HBeAg negative samples and in all the eight samples that were negative for both HBeAg and anti-HBe. The implication of these findings in the management of patients with HBV infection is compelling.
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Affiliation(s)
- Georgina N Odaibo
- Department of Virology, University College Hospital, University of Ibadan, Ibadan, Nigeria.
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Hübschen JM, Mbah PO, Forbi JC, Otegbayo JA, Olinger CM, Charpentier E, Muller CP. Detection of a new subgenotype of hepatitis B virus genotype A in Cameroon but not in neighbouring Nigeria. Clin Microbiol Infect 2011; 17:88-94. [PMID: 20219082 DOI: 10.1111/j.1469-0691.2010.03205.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
To further investigate the genetic diversity of hepatitis B virus (HBV) genotype A in Africa, we analysed 263 HBV strains from Nigeria (n=163) and Cameroon (n=100). Phylogenetic analysis of S fragment sequences attributed 175 strains (66.5%) to genotype E and 88 (33.5%) to genotype A. In Cameroon, genotype A strains were the most prevalent (79/100, 79.0%), whereas, in Nigeria, genotype E was highly dominant (154/163, 94.5%). The genotype A strains grouped with reference strains of subgenotype A3 (n=8), the provisional subgenotype A5 (n=43), a recently reported new variant from Rwanda (n=35), or as outliers (n=2). Ten complete genome sequences obtained from strains that clustered with the new variant from Rwanda formed a separate group supported by a bootstrap value of 96. The between-group distance to other potential or recognized subgenotypes of genotype A was at least 3.81%. Thus, the new group of strains could be considered as a new subgenotype of HBV genotype A, tentatively named 'A7'. Interestingly, the 'A7' strains from Rwanda and Cameroon showed an interspersed clustering, but essentially no other (sub)genotypes were shared between the two countries, suggesting that 'A7' may have evolved in a yet unknown place and may have only relatively recently spread to Rwanda and Western Cameroon. Strains attributed to provisional subgenotype A5 were found for the first time in Cameroon (n=36) and Central Nigeria (n=2), indicating that A5 is more widespread than previously thought.
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Affiliation(s)
- J M Hübschen
- Institute of Immunology, Laboratoire National de Santé/Centre de Recherche Public-Santé, Luxembourg, Luxembourg
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Gulube Z, Chirara M, Kew M, Tanaka Y, Mizokami M, Kramvis A. Molecular characterization of hepatitis B virus isolates from Zimbabwean blood donors. J Med Virol 2011; 83:235-44. [PMID: 21181917 DOI: 10.1002/jmv.21954] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Hepatitis B virus (HBV) is endemic in Africa, being hyperendemic in sub-Saharan Africa. Genotypes A, D, and E circulate in Africa, showing a distinct geographical distribution. The aim of the present study was to determine the HBV genotype distribution in blood donors from different geographical locations in Zimbabwe. Using a restriction fragment polymorphism assay, sequencing of the basic core promoter/precore region and of the complete S open reading frame showed that 29 HBV isolates from geographically distinct regions belong to subgenotype A1. The complete genome of two of these Zimbabwean HBV isolates was sequenced. Forty-four percent of the Zimbabwean HBV isolates (11/23) were characterized by a G1862C missense mutation, which causes a Val to Leu amino acid substitution at position 17 of the precore region. The majority of Zimbabwean HBV isolates clustered with a number of South African HBV isolates, with which they shared characteristic amino acids in the preS1, preS2, and polymerase spacer regions. The wide distribution of subgenotype in Africa, as well as the high intragroup divergence and the geographical clustering of the African and Asian subgenotype A1 HBV isolates indicate that this subgenotype has a long period of endemicity in these regions.
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Affiliation(s)
- Zandiswa Gulube
- Hepatitis Virus Diversity Research Programme (formerly MRC/CANSA/University Molecular Hepatology Research Unit), Faculty of Health Sciences, Department of Internal Medicine, University of the Witwatersrand, Parktown, Johannesburg, South Africa
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Hassan ZK, Hafez MM, Mansor TM, Zekri ARN. Occult HBV infection among Egyptian hepatocellular carcinoma patients. Virol J 2011; 8:90. [PMID: 21371325 PMCID: PMC3058093 DOI: 10.1186/1743-422x-8-90] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2010] [Accepted: 03/03/2011] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Occult HBV infection accelerates the progression of liver fibrosis, cirrhosis, and finally leading to hepatocellular carcinoma (HCC). This study analyzed the occult HBV-genotypes in HCC patients. METHODS To achieve our objective, matched serum and tissue samples were collected from 40 HCC patients. Three sets of primers were used for the HBV-DNA detection by nested-PCR, which cover the HBV-genome; Core, Surface and X genes. Genotyping system based on PCR using type-specific primers was applied on HBV-DNA positive samples. RESULTS Intrahepatic occult HBV-DNA was detected in 62.5%, whereas; Serum occult HBV-DNA were detected in only 22.5% of HCC patients. In patients' positive for both anti-HBs and anti-HBc, 10% had occult HBV in serum. In serologically negative HCV patients, 63% had intrahepatic HBV-DNA, and 21% had HBV-DNA in serum samples. HBV-genotype D (32%) and B (24%) attributed predominantly to intrahepatic HBV infections in HCC patients, whereas HBV-genotype A (4%) and C (8%) infections were the least observed. CONCLUSION This is the first study to show the genotypes of occult HBV infection in HCC Patients. We suggest that B or D may influence the outcome of HBV infection which may lead to the development of HCC.
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Affiliation(s)
- Zeinab K Hassan
- Virology and immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, 1st Kasr El-Aini St, 11197 Cairo, Egypt
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Khaled IAEA, Mahmoud OM, Saleh AF, Bioumie EE. Prevalence of HBV genotypes among Egyptian hepatitis patients. Mol Biol Rep 2010; 38:4353-7. [PMID: 21181276 DOI: 10.1007/s11033-010-0562-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2010] [Accepted: 11/17/2010] [Indexed: 12/15/2022]
Abstract
Phylogenetic analysis has led to the classification of hepatitis B virus into eight genotypes, designated A to H. The genotypes have differences in biological properties and show heterogeneity in their global distribution. These attributes of the genotypes may account not only for differences in the prevalence of hepatitis B virus mutants in various geographic regions, but also makes them responsible for differences in the clinical outcome and response to antiviral treatment in different population groups. Africa is one of the highly endemic regions of HBV with five genotypes (A-E) identified. Almost all patients in the Mediterranean area are infected with genotype D. However, there is little information of genotype distribution in Egypt. A total of 140 Egyptian patients with hepatitis B surface antigen (HBsAg) positive were enrolled in this study. Of the 140 patients, only 100 patients were HBV DNA positive and only these were included in the study. They were classified into 20 patients with acute hepatitis (AH), 75 patients with chronic active hepatitis (CAH) and 5 patients with hepatocellular carcinoma (HCC). HBV genotypes were determined using INNO-LiPA methodology which is based on the reversed hybridization principle. This study showed that genotype D constituted 87% of the total infections (75 CAH cases, 7 AH cases and 5 HCC cases). The other 13% showed mixed infections of D/F. These findings show that the most prevalent genotype in Egypt is genotype D especially in CAH and HCC patients while the mixed type D/F is only encountered in AH.
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Affiliation(s)
- Iman A El Aziz Khaled
- Haematology & Blood Bank, Haematology & Blood Bank Theodor Bilharz Research Institute (TBRI), Cairo, Egypt.
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Dupinay T, Restorp K, Leutscher P, Rousset D, Chemin I, Migliani R, Magnius L, Norder H. High prevalence of hepatitis B virus genotype E in Northern Madagascar indicates a West-African lineage. J Med Virol 2010; 82:1515-26. [PMID: 20648605 DOI: 10.1002/jmv.21865] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The prevalence of hepatitis B virus (HBV) markers was investigated in 563 inhabitants aged 15-55 years from a sugar cane region, Sirama, and from a village, Mataipako, in Northern Madagascar. Serological markers of past or present infection were significantly higher in Sirama, 74% versus 45%. There was no difference in the prevalence of chronic HBsAg carriers, 8.7% versus 8.5% between the two regions. Sequencing the S gene in 45 strains revealed a predominance of genotype E, in 53%, followed by subgenotype A1 in 22%, and genotype D in 18%. Phylogenetic analyses of the genotype E strains showed homology with West African strains. All A1 isolates were similar to Malawi strains. Most genotype D strains were subgenotype D7 and related to strains from Somalia and Tunisia. One genotype D strain formed a branch between Pacific D4 and African D7 strains at neighbor-joining analysis. The pre-core stop mutant was found in 33% of the genotype D strains, 17% of E but not in any A1 strain. The high prevalence and low variability of genotype E strains in only two villages, indicates a rather recent introduction of this genotype into Madagascar from West Africa, possibly through migration or slave trade. The wider spread and genetic relationship of genotype D with East African and Austronesian strains indicate an earlier introduction of this genotype. Molecular epidemiology of HBV may thus be used to complement linguistic and genetic studies on past human migrations in Africa.
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Asim M, Malik A, Sarma MP, Polipalli SK, Begum N, Ahmad I, Khan LA, Husain SA, Akhtar N, Husain S, Thayumanavan L, Singla R, Kar P. Hepatitis B virus BCP, Precore/core, X gene mutations/genotypes and the risk of hepatocellular carcinoma in India. J Med Virol 2010; 82:1115-25. [PMID: 20513073 DOI: 10.1002/jmv.21774] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The study aims to characterize mutations of the HBV genome involving BCP, Precore/core and X regions and also defines HBV genotypes in patients of hepatocellular carcinoma (HCC). The study involved 150 HBV-related HCC cases and 136 HBV-related chronic liver disease patients without HCC as controls. HBV DNA was subjected to mutational analysis using SSCP technique, genotyping by RFLP, and direct nucleotide sequencing. HBV DNA was found in 58.7% (88/150) of the HCC cases and 74.3% (101/136) of controls. HBV mutants were observed in 44.3% of HCC cases and 43.2% of controls. HBV/D was prevalent amongst the patients and controls, followed by HBV/A. The prevalence of the TT1504 mutation in the X gene, the V1753 and T1762/A1764 mutations in the BCP region, and G1914 mutation in the core gene were significantly higher in the HCC group than in the non-HCC group. Multivariate analyses showed that the TT1504, V1753, A1762T/G1764A, and the G1914 mutations and the patient's age, sex, and HBeAg status increased the risk of HCC development significantly. Also, patients with HCC had lower levels of serum albumin, viral load, and platelet counts but higher values of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, and Alpha feto-protein than those of controls (P < 0.001 for all comparisons). HBV/D was the predominant genotype associated with HCC cases seen in India. The presence of different types of HBV mutations, age, sex, HBeAg status, and viral load was found to increase significantly the risk of HCC development in India.
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Affiliation(s)
- Mohammad Asim
- Department of Medicine, Maulana Azad Medical College, University of Delhi, New Delhi, India
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Forbi JC, Vaughan G, Purdy MA, Campo DS, Xia GL, Ganova-Raeva LM, Ramachandran S, Thai H, Khudyakov YE. Epidemic history and evolutionary dynamics of hepatitis B virus infection in two remote communities in rural Nigeria. PLoS One 2010; 5:e11615. [PMID: 20657838 PMCID: PMC2906510 DOI: 10.1371/journal.pone.0011615] [Citation(s) in RCA: 78] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2010] [Accepted: 06/14/2010] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND In Nigeria, hepatitis B virus (HBV) infection has reached hyperendemic levels and its nature and origin have been described as a puzzle. In this study, we investigated the molecular epidemiology and epidemic history of HBV infection in two semi-isolated rural communities in North/Central Nigeria. It was expected that only a few, if any, HBV strains could have been introduced and effectively transmitted among these residents, reflecting limited contacts of these communities with the general population in the country. METHODS AND FINDINGS Despite remoteness and isolation, approximately 11% of the entire population in these communities was HBV-DNA seropositive. Analyses of the S-gene sequences obtained from 55 HBV-seropositive individuals showed the circulation of 37 distinct HBV variants. These HBV isolates belong predominantly to genotype E (HBV/E) (n=53, 96.4%), with only 2 classified as sub-genotype A3 (HBV/A3). Phylogenetic analysis showed extensive intermixing between HBV/E variants identified in these communities and different countries in Africa. Quasispecies analysis of 22 HBV/E strains using end-point limiting-dilution real-time PCR, sequencing and median joining networks showed extensive intra-host heterogeneity and inter-host variant sharing. To investigate events that resulted in such remarkable HBV/E diversity, HBV full-size genome sequences were obtained from 47 HBV/E infected persons and P gene was subjected to Bayesian coalescent analysis. The time to the most recent common ancestor (tMRCA) for these HBV/E variants was estimated to be year 1952 (95% highest posterior density (95% HPD): 1927-1970). Using additional HBV/E sequences from other African countries, the tMRCA was estimated to be year 1948 (95% HPD: 1924-1966), indicating that HBV/E in these remote communities has a similar time of origin with multiple HBV/E variants broadly circulating in West/Central Africa. Phylogenetic analysis and statistical neutrality tests suggested rapid HBV/E population expansion. Additionally, skyline plot analysis showed an increase in the size of the HBV/E-infected population over the last approximately 30-40 years. CONCLUSIONS Our data suggest a massive introduction and relatively recent HBV/E expansion in the human population in Africa. Collectively, these data show a significant shift in the HBV/E epidemic dynamics in Africa over the last century.
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Affiliation(s)
- Joseph C Forbi
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
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Alvarado Mora MV, Romano CM, Gomes-Gouvêa MS, Gutierrez MF, Carrilho FJ, Pinho JRR. Molecular epidemiology and genetic diversity of hepatitis B virus genotype E in an isolated Afro-Colombian community. J Gen Virol 2009; 91:501-8. [PMID: 19846674 DOI: 10.1099/vir.0.015958-0] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Hepatitis B virus (HBV) infection is a significant public health concern with 350 million chronic carriers worldwide. Eight HBV genotypes (A-H) have been described so far. Genotype E (HBV/E) is widely distributed in West Africa and has rarely been found in other continents, except for a few cases in individuals with an African background. In this study, we characterized HBV genotypes in Quibdó, Colombia, by partial S/P gene sequencing, and found, for the first time, HBV/E circulating in nine Afro-Colombian patients who had no recent contact with Africa. The presence of HBV/E in this community as a monophyletic group suggests that it was a result of a recent introduction by some Afro-descendent contact or, alternatively, that the virus came with slaves brought to Colombia. By using sequences with sampling dates, we estimated the substitution rate to be about 3.2 x 10(-4) substitutions per site per year, which resulted in a time to the most recent common ancestor (TMRCA) of 29 years. In parallel, we also estimated the TMRCA for HBV/E by using two previously estimated substitution rates (7.7 x 10(-4) and 1.5 x 10(-5) substitutions per site per year). The TMRCA was around 35 years under the higher rate and 1500 years under the slower rate. In sum, this work reports for the first time the presence of an exclusively African HBV genotype circulating in South America. We also discuss the time of the entry of this virus into America based on different substitution rates estimated for HBV.
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Affiliation(s)
- Mónica Viviana Alvarado Mora
- Laboratory of Gastroenterology and Hepatology, São Paulo Institute of Tropical Medicine and Department of Gastroenterology, School of Medicine, University of São Paulo, Brazil.
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Full-length genome characterization of hepatitis B virus genotype H strain isolated from serum samples collected from two chronically infected patients in Argentina. J Clin Microbiol 2009; 47:4191-3. [PMID: 19794035 DOI: 10.1128/jcm.01337-09] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
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Garmiri P, Loua A, Haba N, Candotti D, Allain JP. Deletions and recombinations in the core region of hepatitis B virus genotype E strains from asymptomatic blood donors in Guinea, west Africa. J Gen Virol 2009; 90:2442-2451. [PMID: 19535503 DOI: 10.1099/vir.0.012013-0] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The prevalence of hepatitis B virus (HBV) surface antigen (HBsAg) chronic carriage in west Africa is the highest in the world, but its molecular epidemiology remains relatively poorly investigated. Plasma samples from random asymptomatic carriers of HBsAg in Conakry, Guinea, were studied and the complete genome sequences of 81 strains were obtained. Three additional samples from Kumasi, Ghana, were also included in the analysis. Phylogenetic analyses confirmed the dominance of genotype E (95.1%), including 8.6% of strains (viral load, 5x10(3)-2.6x10(8) IU ml(-1)) comprising dominant variants with large deletions in the core region and minority wild-type variants. The presence of two different patterns of deletions in two and four donors suggested targeted genome fragility between nt 1979 and 2314. The remaining sequences included one subgenotype A3 (1%) and six A/E recombinant forms (4-7%). A/E strains with identical points of recombination in three donors suggested strongly that these recombinant HBV strains are circulating and transmitted in the population. Recombination points were concentrated in the core gene. The detection of similar A/E recombinant strains in Ghana suggested a geographical extension of recombinant HBV to the region. The quasispecies of one additional Ghanaian strain sequenced in the pre-surface/surface region resolved into dominant clones of either the A or E genotype, but also three different patterns of A/E recombinant variants. The observation that both deletions of genotype E strains and A/E recombination points are mostly located in the core gene at specific positions indicates a region of the genome where genetic rearrangements preferentially take place.
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Affiliation(s)
- Penelope Garmiri
- Division of Transfusion Medicine, Department of Haematology, University of Cambridge, Cambridge, UK
| | - André Loua
- National Blood Transfusion Center, Conakry, Guinea
| | | | - Daniel Candotti
- National Health Service Blood and Transplant, Cambridge Blood Centre, Cambridge, UK
| | - Jean-Pierre Allain
- Division of Transfusion Medicine, Department of Haematology, University of Cambridge, Cambridge, UK
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33
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Hepatitis B virus genotype E variability in Africa. J Clin Virol 2008; 43:376-80. [PMID: 18922739 DOI: 10.1016/j.jcv.2008.08.018] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2008] [Accepted: 08/14/2008] [Indexed: 02/06/2023]
Abstract
BACKGROUND In sub-Saharan Africa, genotype E is the predominant genotype throughout a vast region spanning from Senegal to Namibia and extending to the Central African Republic in the East. Despite its wide geographic distribution and the high prevalence throughout this genotype E crescent, this genotype has a very low genetic diversity. OBJECTIVES Here we review our current understanding of genotype E reanalysing all currently available sequences of the S gene and the complete genome. RESULTS Phylogenetic analysis of the complete genome sequences confirmed a previously suggested South-West/Central African cluster and several lineages of West African sequences. The overall mean genetic distance was 1.71%, with the more Southern countries of the genotype E crescent exhibiting lower distances than the Northern countries. CONCLUSIONS Genotype E seems to have a longer natural history in the Northern part of the genotype E crescent than in the Southern countries. As genotype E is essentially absent from the Americas despite the Afro-American slave trade until at least the beginning of the 19th century, genotype E strains may have been introduced into the general African population only within the past 200 years. How the virus may have spread throughout the genotype E crescent warrants further investigation.
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Olinger CM, Lazouskaya NV, Eremin VF, Muller CP. Multiple genotypes and subtypes of hepatitis B and C viruses in Belarus: similarities with Russia and western European influences. Clin Microbiol Infect 2008; 14:575-81. [PMID: 18373690 DOI: 10.1111/j.1469-0691.2008.01988.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The Republic of Belarus reports a seroprevalence of 4.8% for hepatitis B virus (HBV) and 1.26% for hepatitis C virus (HCV), but little is known about the molecular characteristics of the circulating viruses. This study analysed 69 HBV surface antigen (HBsAg)-positive and 113 anti-HCV-positive donors attending a national reference hospital in Minsk. Among the HCV patients, 70% were co-infected with human immunodeficiency virus (HIV). Phylogenetic analysis of 12 complete genomes and 31 partial HBV sequences, as well as 78 core/E1 HCV sequences, revealed that multiple genotypes and subtypes of both viruses were circulating in Belarus. Of the HBV strains, 11.6% were genotype A2 and 88.6% were genotype D. The genotype D strains segregated into four recently described subtypes, with D2 being the most prevalent (58.1%), followed by D3 (16.3%), D1 (11.6%) and D4 (2.3%), but with inter-subtypic distances lower than the minimal 4% distance proposed to define subtypes. The 78 HCV strains belonged to subtypes 1b (53.8%), 3a (38.5%), 1a (5.1%), 4a (1.3%) and 4d (1.3%). Subtype 1b was less prevalent (45.1% vs. 70.4%) among HCV/HIV co-infected donors, while subtype 3a was more prevalent (29.6% vs. 43.1%). The relative prevalence of HBV and HCV genotypes in Belarus corresponded to the prevalence in Russia, although with a clear European influence that reflected the socio-political context of the country.
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Affiliation(s)
- C M Olinger
- Institute of Immunology, National Public Health Laboratory, Luxembourg, Luxembourg, USA
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[Characterization of hepatitis B virus strains from the Central African Republic: preliminary results]. ACTA ACUST UNITED AC 2008; 56:310-3. [PMID: 18321662 DOI: 10.1016/j.patbio.2007.12.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2007] [Accepted: 12/14/2007] [Indexed: 12/17/2022]
Abstract
OBJECTIVES Genotyping of Hepatitis B virus (HBV) strains from patients in Central African Republic and comparison with results obtained in other African countries. PATIENTS AND METHODS Sera were collected from patients admitted with symptoms of acute or chronic hepatitis to the "Hôpital de l'Amitié de Bangui", Central African Republic (CAR). The complete sequence of preS2/S gene has been defined for determining genotypes. RESULTS Hundred and ninety-six sera were collected from 112 men and 84 women. Ninety-two percent of patients had contact with HBV (anti-HBc postitive) and the HBsAg prevalence was about 62%. HBV DNA was detected in 66% of HBsAg positive sera. No HBV-DNA was evidenced among patients with negative HBsAg. Ninety-three percent of the HBV strains belonged to genotype E; one (3.4%) belonged to genotype A1, and one (3.4%) belonged to genotype D. CONCLUSIONS The high prevalence of HBV infection in the studied population is due to their recruitment. The genotype E is predominant in CAR and the intragroup variability of HBV genotype E reached only 1.8%. Genotypes A and D were less common in CAR their presence may be explained by importation.
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36
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Forbi JC, Gabadi S, Alabi R, Iperepolu HO, Pam CR, Entonu PE, Agwale SM. The role of triple infection with hepatitis B virus, hepatitis C virus, and human immunodeficiency virus (HIV) type-1 on CD4+ lymphocyte levels in the highly HIV infected population of North-Central Nigeria. Mem Inst Oswaldo Cruz 2008; 102:535-7. [PMID: 17612776 DOI: 10.1590/s0074-02762007005000025] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2006] [Accepted: 03/19/2007] [Indexed: 12/25/2022] Open
Abstract
We set out to determine the seroprevalence of hepatitis B and C among human immunodeficiency virus type-1 (HIV-1) infected individuals in North-Central Nigeria to define the influence of these infections on CD4+ lymphocytes cells among our patients as access to antiretroviral therapy improves across the Nigerian nation. The CD4+ values of 180 confirmed HIV-1 infected individuals were enumerated using a superior fluorescence-activated cell sorter system. These patients were tested for the presence of hepatitis B surface antigen and anti-hepatitis C virus (HCV) using third generation enzyme-linked immunosorbent assays. Fifty (27.8%) patients had active hepatitis B virus (HBV) infection while 33 (18.3%) tested positive for anti-HCV antibody. Of these infections, 110 (61.1%), 37 (20.6%), and 20 (11.1%) had HIV only, HBV/HIV-only, and HCV/HIV-only respectively. A HBV/HCV/HIV coinfection prevalence of 7.2% (13 patients) was recorded. Patients coinfected with HIV/HBV/HCV appeared to have lower CD4+ counts (mean = 107 cells/microl; AIDS defining) when compared to HBV/HIV-only (mean = 377 cells/microl), HCV/HIV-only (mean = 373 cells/microl) and patients with mono HIV infection (mean = 478 cells/microl). Coinfection with HBV or HCV is relatively common among HIV-infected patients in Nigeria and should be a big consideration in the initiation and choice of therapy.
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Affiliation(s)
- J C Forbi
- Virology Laboratory, Innovative Biotech-Keffi No. 1, Keffi, Nasarawa State, Nigeria
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Bekondi C, Olinger CM, Boua N, Talarmin A, Muller CP, Le Faou A, Venard V. Central African Republic is part of the West-African hepatitis B virus genotype E crescent. J Clin Virol 2007; 40:31-7. [PMID: 17689139 DOI: 10.1016/j.jcv.2007.05.009] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2007] [Revised: 04/25/2007] [Accepted: 05/21/2007] [Indexed: 12/12/2022]
Abstract
BACKGROUND Recent studies have shown that Hepatitis B virus (HBV) genotype E predominates in a vast crescent in West-Africa spanning from Senegal to Angola. OBJECTIVES To determine whether HBV strains in the Central African Republic (CAR) belong predominately to the homogeneous West-African genotype E or whether they are more closely related to genotypes found in East Africa. STUDY DESIGN Serum samples were randomly collected from 196 patients admitted with symptoms of acute or chronic hepatitis to the Central Hospital in Bangui. Thirty complete and 36 partial sequences of HBV strains were obtained. RESULTS Ninety-four percent (62/66) of the strains belonged to genotype E, while genotype A1, most closely related to a strain from Tanzania and genotype D were detected in only one and three samples, respectively. One strain presented a recombination between the S and X gene of a genotype E precursor and a partial PreC/C gene of a genotype D precursor. CONCLUSIONS Genotype E is predominant in CAR with little overlap with genotypes from Eastern Africa, extending the West-African HBV genotype E crescent further to the East.
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Affiliation(s)
- Claudine Bekondi
- Laboratoire de Virologie, Unité des Rétrovirus et des Hépatites virales, Institut Pasteur de Bangui, rue Pasteur, BP 923 Bangui, République Centrafricaine
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Kramvis A, Kew MC. Epidemiology of hepatitis B virus in Africa, its genotypes and clinical associations of genotypes. Hepatol Res 2007; 37:S9-S19. [PMID: 17627641 DOI: 10.1111/j.1872-034x.2007.00098.x] [Citation(s) in RCA: 222] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Of approximately 360 million people in the world chronically infected with hepatitis B virus (HBV), 65 million reside in Africa. Thus, Africa, with 12% of the world's population, carries approximately 18% of the global burden of HBV infection, with hepatocellular carcinoma and cirrhosis accounting for 2% of the continent's annual deaths. Despite HBV being endemic or hyperendemic in Africa, there is a paucity of data on the genotypes and their distribution. Genotype A is found mainly in southern, eastern and central Africa. Most African genotype A strains belong to subgenotype A1, with subgenotype A3 found in western Africa. Genotype D prevails in northern countries and genotype E in western and central Africa. Ithas become increasingly evident that heterogeneity in the global distribution of HBV genotypes may be responsible for differences in the clinical outcomes of HBV infections and the response to antiviral treatment and vaccination. A limited number of studies have been published relating genotypes to clinical outcomes in African countries. Because observations from other regions of the world can not be extrapolated from one locale to another, the HBV strains circulating in Africa should be studied and related to clinical outcomes.
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Affiliation(s)
- Anna Kramvis
- MRC/University Molecular Hepatology Research Unit, Department of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa
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Olinger CM, Weber B, Otegbayo JA, Ammerlaan W, van der Taelem-Brulé N, Muller CP. Hepatitis B virus genotype E surface antigen detection with different immunoassays and diagnostic impact of mutations in the preS/S gene. Med Microbiol Immunol 2007; 196:247-52. [PMID: 17503077 DOI: 10.1007/s00430-007-0050-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2007] [Indexed: 12/17/2022]
Abstract
The major neutralizing epitope, the "a" determinant of the hepatitis B virus (HBV) genotype E surface antigen (HBsAg) is most divergent from that of genotype A, which is used for preparing monoclonal antibodies used in commercially available HBV reagents. To evaluate the performance of the latest generation of HBsAg detection assays with respect to genotype E HBsAg. Three commercial assays were evaluated using sera from 200 Nigerian patients compared to the preS/S sequence of DNA positive samples. Out of 200 samples, 61 and 103 gave concordant positive and negative results between the three HBsAg assays. Of 36 samples with discordant results, 35 were confirmed negative by neutralisation. One of the three assays showed significantly high rate of false positives (29 of 35). DNA positive samples with no detectable HBsAg or reduced HBsAg detection signals (<75% of mean signal obtained with HBsAg positive samples) revealed several mutations (V14A, F46S, N48T, L49R, I49T, D51G, A53V, P54L, Q82P, F83C, L127P, A184V, T189I, S204N, V224A), mostly outside the a-determinant. Several of these mutations are found as wild type nucleotides normally in genotype A and only exceptionally in genotype E. All three assays showed comparable sensitivities for genotype E HBsAg detection (98.4-100%) but differed considerably in specificity (84-99%). Failure to detect HBsAg antigen and differences in signal intensity were mainly associated with mutations in the preS/S gene outside the "a" determinant.
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Affiliation(s)
- Christophe M Olinger
- Institute of Immunology, National Public Health Laboratory, 20a, rue Auguste Lumière, 1950, Luxembourg, Luxembourg.
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40
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Olinger CM, Venard V, Njayou M, Oyefolu AOB, Maïga I, Kemp AJ, Omilabu SA, le Faou A, Muller CP. Phylogenetic analysis of the precore/core gene of hepatitis B virus genotypes E and A in West Africa: new subtypes, mixed infections and recombinations. J Gen Virol 2006; 87:1163-1173. [PMID: 16603517 DOI: 10.1099/vir.0.81614-0] [Citation(s) in RCA: 118] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
One hundred and twenty-two new hepatitis B virus (HBV) preC/C sequences and three complete genomes from three major countries in West Africa were analysed. The majority of sequences were of genotype E and the only other genotype found was genotype A. Although for genotype E sequences, the genetic diversity of the preC/C gene was about two to three times higher than that of the preS/S gene, it was still considerably lower than that for genotype A sequences. The HBV/E preC/C gene was related most closely to subgenotype D1 and D2 sequences. Evidence of recombination was found in two strains that were of genotype A in the preS/S gene and of genotype E in the preC/C gene. The genotype A strains from Cameroon, Mali and Nigeria could be divided phylogenetically into three subtypes, A3 and two new subtypes, tentatively designated A4 and A5. Each subtype presented a genetic diversity of 2.19-3.85 % and intersubtype distances of 4.47-5.97 %. Interestingly, one sample from Nigeria showed evidence of a triple recombination of genotypes E/D and A, separated by a genotype G-specific insert of 36 bp. Of 110 patients, 19 (17.3 %) showed a coinfection of genotypes A and E, mostly in human immunodeficiency virus-positive children from Cameroon. Thus, in Cameroon, where both genotypes coexist, 37 % of all individuals tested had mixed infections. The low genetic variability in the preC/C gene of genotype E supports our previous speculation about a relatively short evolutionary history of this genotype, in contrast to the subtype-rich African genotype A strains.
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Affiliation(s)
- Christophe M Olinger
- Institute of Immunology, National Public Health Laboratory, 20A rue Auguste-Lumière, L-1950 Luxembourg, Luxembourg
| | - Véronique Venard
- Unité Mixte de Recherche 7565 UHP-CNRS, Laboratoire de Bactériologie-Virologie, Faculté de Médecine, Vandœuvre-lès-Nancy, France
| | - Mounjohou Njayou
- Laboratoire de Microbiologie Microbienne, Centre de Biotechnologie - Nkolbisson, Yaoundé, Cameroon
| | - Akeeb O Bola Oyefolu
- Department of Medical Microbiology and Parasitology and Department of Medicine, College of Medicine of the University of Lagos, Nigeria
| | - Ibrahim Maïga
- Laboratoire de Biologie Médicale, Hôpital du Point G, Bamako, Mali
| | - Alain J Kemp
- Institute of Immunology, National Public Health Laboratory, 20A rue Auguste-Lumière, L-1950 Luxembourg, Luxembourg
| | - Sunday A Omilabu
- Department of Medical Microbiology and Parasitology and Department of Medicine, College of Medicine of the University of Lagos, Nigeria
| | - Alain le Faou
- Unité Mixte de Recherche 7565 UHP-CNRS, Laboratoire de Bactériologie-Virologie, Faculté de Médecine, Vandœuvre-lès-Nancy, France
| | - Claude P Muller
- Institute of Immunology, National Public Health Laboratory, 20A rue Auguste-Lumière, L-1950 Luxembourg, Luxembourg
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41
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Ganne-Carrié N, Williams V, Kaddouri H, Trinchet JC, Dziri-Mendil S, Alloui C, Hawajri NA, Dény P, Beaugrand M, Gordien E. Significance of hepatitis B virus genotypes A to E in a cohort of patients with chronic hepatitis B in the Seine Saint Denis District of Paris (France). J Med Virol 2006; 78:335-40. [PMID: 16419113 DOI: 10.1002/jmv.20545] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The aim of this study was to examine the genetic variability of the hepatitis B virus (HBV) and its significance. HBV genotypes, core promoter and precore mutants were characterized in 109 consecutive patients with biopsy-proven HBV chronic hepatitis. Genotypes A (26.6%), B (12.8%), C (18.3%), D (18.3%), and E (14.7%) indicate a wide genotypic distribution. Patients were from Asia (30.3%), Europe (28.4%), Sub Saharan Africa (23.9%), the Caribbean (10.1%), North Africa (5.5%), and Madagascar (1.8%). HBV genotypes A and D (HBV/A and /D) infected all subgroups except Asian patients. HBV/B or /C were found in 97% of Asian patients, whereas HBV/E only infected sub-Saharan African and Caribbean patients. Differences according to genotypes were: an increased prevalence of anti-HBe antibodies in patients infected with HBV/D (P = 0.003), higher serum transaminases in patients infected with HBV/A and/D (P = 0.043), more severe liver fibrosis in patients infected with HBV/A, /C and/D (P = 0.02). Precore and core promoter mutants were found in 87% of anti-HBe positive patients, and were associated with HBV/D (P = 0.04) and severe liver fibrosis (P = 0.002). It is concluded that HBV genotypes A, B, C, D, and E circulate in the Seine Saint Denis District, reflecting the geographical origin of patients. HBV/A, /C and/D seem to be associated with more severe hepatic disease.
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Affiliation(s)
- Nathalie Ganne-Carrié
- Service d'Hépato-Gastroentérologie, Hôpital Jean Verdier (Bondy), Assistance Publique-Hôpitaux de Paris, UPRES 3409, UFR Santé Médecine Biologie Humaine, Université Paris 13, France.
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42
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Dal Molin G, Poli A, Crocè LS, D'Agaro P, Biagi C, Comar M, Tiribelli C, Campello C. Hepatitis B virus genotypes, core promoter variants, and precore stop codon variants in patients infected chronically in North-Eastern Italy. J Med Virol 2006; 78:734-40. [PMID: 16628589 DOI: 10.1002/jmv.20616] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The hepatitis B virus (HBV) genotypes distribution and the core promoter (CP)/precore (PC) variability were evaluated by a line probe assay in 272 patients infected chronically enrolled consecutively in an area of the North-Eastern Italy. Seven out of the eight genotypes were detected. Italian subjects (83% of the sample) were infected mainly by genotype D (73%) and A (26%); genotype F, and genotype H, were detected only in one subject. In foreigners, the genotype distribution reflected the distribution described for the areas of origin, that is, in Asia genotypes B, C, and D; in Africa genotypes A and E. CP and PC variants prevalence rates were 51% and 60%, respectively, and were significantly higher in Italian patients, probably in relation to their older age. In the analysis restricted to genotypes A and D, PC wild type was linked strongly to genotype A (OR = 4.08, 95% CI = 3.07-5.43, P < 0.0001). In genotype A-infected patients, only e seroconversion was associated significantly with CP variants. In genotype D-infected subjects, CP variants were linked significantly to older age and to a higher e seroconversion rate, while PC variants also showed a strong relationship with an ALT lower activity and a lower viral load. In multivariate analysis, HBeAg positivity was associated strongly and independently with younger age, genotype A and CP wild type. Independent determinants of higher viral loads were recognized by increasing age, in male gender and concomitant presence of HBeAg and the CP wild type virus.
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Affiliation(s)
- Gianna Dal Molin
- Department of Public Medicine Sciences, UCO Hygiene and Preventive Medicine, University of Trieste, and IRCCS Burlo Garofolo, Trieste, Italy
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43
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Makuwa M, Souquière S, Telfer P, Apetrei C, Vray M, Bedjabaga I, Mouinga-Ondeme A, Onanga R, Marx PA, Kazanji M, Roques P, Simon F. Identification of hepatitis B virus subgenotype A3 in rural Gabon. J Med Virol 2006; 78:1175-84. [PMID: 16847965 DOI: 10.1002/jmv.20678] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
An hepatitis B virus (HBV) molecular survey was conducted in five remote villages in the equatorial forest in Gabon, Central Africa. Two hundred seventy out of 311 inhabitants (86.8%) were HBV-infected or had evidence of past HBV infection. Chronic hepatitis corresponding to hepatitis B surface antigen (HBsAg) positivity was suspected in 27 (8.6%) of the HBV-infected subjects. High HBV viral loads were detected mainly in children aged 4-7 years. The pre-S/S domains were sequenced in 13 cases and 12 strains belonged to HBV-A genotype. In one case we found evidence for recombination between genotypes A and E. Phylogenetic analysis revealed that Gabonese HBV strains were distinct from HBV-A subgenotypes (A1 and A2). These new HBV strains from Gabon clustered with previously reported HBV-A3 subgenotype strains from Cameroon and Democratic Republic of Congo. The analysis of the pre-S2 domain allowed us to determine two amino acid substitutions (N/152/S and N/174/T) specific to the Central African HBV-A3 subgenotype strains and one amino acid substitution (P/155/Q) unique to these new Gabonese HBV-A3 subgenotype isolates. Two full genome sequences of two new Gabonese HBV isolates are also presented and confirm the distinctive HBV-Gab-A3 cluster.
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Affiliation(s)
- Maria Makuwa
- Laboratoire de Rétrovirologie, Centre International de Recherches Médicales, CIRMF, Franceville, Gabon.
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Fujiwara K, Tanaka Y, Orito E, Ohno T, Kato T, Sugihara K, Hasegawa I, Sakurai M, Ito K, Ozasa A, Sakamoto Y, Arita I, El-Gohary A, Benoit A, Ogoundele-Akplogan SI, Yoshihara N, Ueda R, Mizokami M. Distribution of HBV genotypes among HBV carriers in Benin:phylogenetic analysis and virological characteristics of HBV genotype E. World J Gastroenterol 2005; 11:6410-5. [PMID: 16425408 PMCID: PMC4355778 DOI: 10.3748/wjg.v11.i41.6410] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the distribution of Hepatitis B virus (HBV) genotypes in Benin, and to clarify the virological characteristics of the dominant genotype.
METHODS: Among 500 blood donors in Benin, 21 HBsAg-positive donors were enrolled in the study. HBV genotypes were determined by enzyme immunoassay and restriction fragment length polymorphism. Complete genome sequences were determined by PCR and direct sequencing.
RESULTS: HBV genotype E (HBV/E) was detected in 20/21 (95.2%), and HBV/A in 1/21 (4.8%). From the age-specific prevalence of HBeAg to anti-HBe seroconversion (SC) in 19 HBV/E subjects, SC was estimated to occur frequently in late teens in HBV/E. The comparison of four complete HBV/E genomes from HBeAg-positive subjects in this study and five HBV/E sequences recruited from the database revealed that HBV/E was distributed throughout West Africa with very low genetic diversity (nucleotide homology 96.7-99.2%). Based on the sequences in the basic core promoter (BCP) to precore region of the nine HBV/E isolates compared to those of the other genotypes, a nucleotide substitution in the BCP, G1757A, was observed in HBV/E.
CONCLUSION: HBV/E is predominant in the Republic of Benin, and SC is estimated to occur in late teens in HBV/E. The specific nucleotide substitution G1757A in BCP, which might influence the virological characteristics, is observed in HBV/E.
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Affiliation(s)
- Kei Fujiwara
- Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho, Nagoya 467-8601, Japan
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45
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Kramvis A, Kew MC. Relationship of genotypes of hepatitis B virus to mutations, disease progression and response to antiviral therapy. J Viral Hepat 2005; 12:456-64. [PMID: 16108759 DOI: 10.1111/j.1365-2893.2005.00624.x] [Citation(s) in RCA: 143] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Phylogenetic analysis has led to the classification of hepatitis B virus into eight genotypes, designated A to H. The genotypes have differences in biological properties and show heterogeneity in their global distribution. These attributes of the genotypes may account not only for differences in the prevalence of hepatitis B virus mutants in various geographic regions, but also be responsible for differences in the clinical outcome and response to antiviral treatment in different population groups.
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Affiliation(s)
- A Kramvis
- MRC/University Molecular Hepatology Research Unit, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa.
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46
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Shibayama T, Masuda G, Ajisawa A, Hiruma K, Tsuda F, Nishizawa T, Takahashi M, Okamoto H. Characterization of seven genotypes (A to E, G and H) of hepatitis B virus recovered from Japanese patients infected with human immunodeficiency virus type 1. J Med Virol 2005; 76:24-32. [PMID: 15779062 DOI: 10.1002/jmv.20319] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
To investigate the prevalence of hepatitis B virus (HBV) genotypes and characteristics of HBV isolates among Japanese patients infected with human immunodeficiency virus type 1 (HIV), serum samples collected between September 1990 and March 2002 from 471 HIV-infected patients (age, 38.8 +/- 11.4 [mean +/- standard deviation] years; male, 90%) were tested for hepatitis B surface antigen (HBsAg) and HBV DNA. Positivity for HBsAg and HBV DNA was seen in 42 patients (8.9%), 41 of whom had contracted HIV infection through sexual activity and 1 had hemophilia. Genotypes of HBV were determined by comparative and phylogenetic analyses of the S gene sequence (396 nucleotides [nt]). The distribution of HBV genotypes among the 42 HBV-viremic patients was: A (50%), B (5%), C (24%), D (5%), E (2%), H (10%), A plus D (2%), A plus G (2%). The hemophilia patient had HBV genotype D. Genotypes E, G, and H which had not been reported in Japan, were found in one patient each who had traveled to Zambia, the US, and South America, respectively. Genotypes A and D, which are rare in Japan, were found in patients who had no history of traveling abroad. The entire genome of the HB-JI411 (genotype E [3,212 nt]), HB-JI444G (genotype G [3,248 nt]), and HB-JI260 (genotype H [3,218 nt]) isolates had the highest identity of 98.3%, 99.9%, and 98.5%, respectively, with reported HBV isolates of the same genotype. Most Japanese patients coinfected with HIV and HBV had HBV genotypes that are found rarely or had not been reported in Japan.
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Affiliation(s)
- Takao Shibayama
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
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47
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Pujol FH, Devesa M. Genotypic variability of hepatitis viruses associated with chronic infection and the development of hepatocellular carcinoma. J Clin Gastroenterol 2005; 39:611-8. [PMID: 16000930 DOI: 10.1097/01.mcg.0000170770.49394.92] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
At least five hepatitis viruses are known to date. Infection by enterically transmitted viruses (HAV and HEV) is generally benign compared with the disease caused by parenterally transmitted viruses (HBV, HCV, and HDV). Chronic infection by HBV is common and may evolve to cirrhosis and hepatocellular carcinoma (HCC). Eight HBV genotypes (A-H) have been described, with the South American genotype F being the most divergent. Seven clades of HDV have been described; among them, the South American genotype III is associated to a high frequency of fulminant hepatitis. HCV infection leads to a high rate of chronicity and HCC. From the six HCV genotypes, infection with genotype 1 might have the worst prognostic. Chronic infection by HCV and HBV is the major risk factor for HCC, which occurs, in the majority of the cases, as a consequence of cirrhosis. However, there is growing evidence that some HBV and HCV proteins might contribute to the generation of HCC. Some HBV and HCV variants and specific mutations within the viral genomes might be more frequently associated with the evolution to HCC. Although more studies are needed, emerging evidence indicates that it might be important to address the genetic variability of these viruses and their contribution to the development of HCC.
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Affiliation(s)
- Flor H Pujol
- Laboratoria de Virología Molecular, Caracas, Venezuela.
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48
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Maïga I, Le Faou A, Muller CP, Venard V. Unexpected high prevalence of hepatitis B and HIV infections in Malian medical students. Eur J Clin Microbiol Infect Dis 2005; 24:501-2. [PMID: 15973511 DOI: 10.1007/s10096-005-1359-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Affiliation(s)
- I Maïga
- Faculté de Médecine et de Pharmacie, Laboratoire de Microbiologie de l'hôpital du point G, Bamako, Mali
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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] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Genotypes A, D, and E of the hepatitis B virus (HBV) circulate in southern Africa, with genotype A predominating. Their hepatocarcinogenic potential in Bantu-speaking sub-saharan Africans is, however, unknown. Using a case/control format, we investigated the hepatocarcinogenic potential of these genotypes and subgenotype A1 of genotype A, which accounts for the great majority of genotype A isolates. HBV isolates from 111 unselected Bantu-speaking sub-saharan Africans with hepatocellular carcinoma (HCC) and 111 matched asymptomatic chronic carriers, serving as controls, were genotyped using the method of [Lindh et al. (1997): J Infect Dis 175:1285-1293]. Subgenotypes of genotype A were determined using an in-house restriction fragment length polymorphism assay. Genotype A was present in 96 (86.5%) of patients with HCC and 76 (68.5%) of the carriers, giving a 4.5-fold (95% confidence limits: 1.86, 10.90) increased risk of HCC in carriers infected with genotype A compared with those infected with non-A genotypes. HCC patients infected with genotype A were significantly younger than those infected with non-A genotypes (P = 0.02). The distributions between these two groups according to sex, geographic background, and tribe were not significantly different. Subgenotype A1 was present in all of the 77 cancer patients and 69 of 70 carriers analyzed, yielding a relative risk of 4.21 (95% confidence limits: 1.73,10.23) of HCC in those infected with subgenotype A1 compared with those infected with non-A genotypes. Genotype A has a greater hepatocarcinogenic potential than non-A genotypes in Bantu-speaking sub-saharan Africans and this is entirely attributable to subgenotype A1.
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Affiliation(s)
- Michael C Kew
- MRC/CANSA/University Molecular Hepatology Research Unit, Department of Medicine, Medical School, University of the Witwatersrand, 7 York Road, Parktown 2193, Johannesburg, South Africa.
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50
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Kramvis A, Kew M, François G. Hepatitis B virus genotypes. Vaccine 2005; 23:2409-23. [PMID: 15752827 DOI: 10.1016/j.vaccine.2004.10.045] [Citation(s) in RCA: 255] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2004] [Revised: 09/27/2004] [Accepted: 10/14/2004] [Indexed: 12/17/2022]
Abstract
Eight genotypes of hepatitis B virus (A-H) are currently recognized, and subgenotypes have recently been described in four of these genotypes (A, B, C and F). The genotypes show a distinct geographical distribution between and even within regions, and are proving to be an invaluable tool in tracing the molecular evolution and patterns and modes of spread of hepatitis B virus. Structural and functional differences between genotypes can influence the severity, course and likelihood of complications, and response to treatment of hepatitis B virus infection and possibly vaccination against the virus. Although the number of studies on these genotypes has increased dramatically during recent years, much remains to be learnt about their full implications.
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Affiliation(s)
- Anna Kramvis
- MRC/University Molecular Hepatology Research Unit, Department of Medicine, University of the Witwatersrand Medical School, 7 York Road, Parktown, 2193 Johannesburg, South Africa.
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