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      Broad Range of Hepatitis B Virus (HBV) Patterns, Dual Circulation of Quasi-Subgenotype A3 and HBV/E and Heterogeneous HBV Mutations in HIV-Positive Patients in Gabon

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          Abstract

          Integrated data on hepatitis B virus (HBV) patterns, HBV genotypes and mutations are lacking in human immunodeficiency virus type 1 (HIV-1) co-infected patients from Africa. This survey was conducted in 2010–2013 among 762 HIV-1-positive adults from Gabon who were predominantly treated with 3TC-based antiretroviral treatment. HBV patterns were identified using immunoassays detecting total antibody to hepatitis B core antigen (HBcAb), hepatitis B surface antigen (HBsAg), IgM HBcAb, hepatitis B e antigen (HBeAg), antibody to HBsAg (HBsAb) and an in-house real-time PCR test for HBV DNA quantification. Occult hepatitis B (OBI) was defined by the presence of isolated anti-HBc with detectable serum HBV DNA. HBV genotypes and HBV mutations were analyzed by PCR-direct sequencing method. Seventy-one (9.3%) patients tested positive for HBsAg, including one with acute hepatitis B (0.1%; 95% CI, 0.0%-0.2%), nine with HBeAg-positive chronic hepatitis B (CHB) (1.2%; 95% CI, 0.6%–2.2%), 16 with HBeAg-negative CHB (2.1%; 95% CI, 1.2%–3.3%) and 45 inactive HBV carriers (5.9%; 95% CI, 4.4%–7.8%). Sixty-one (8.0%; 95% CI, 6.2%–10.1%) patients showed OBI. Treated patients showed similar HBV DNA levels to those obtained in untreated patients, regardless of HBV patterns. Around 15.0% of OBI patients showed high (>1,000 UI/mL) viremia. The mutation M204V/I conferring resistance to 3TC was more common in HBV/A (47.4%) than in HBV/E isolates (0%) ( P = .04). Our findings encouraged clinicians to promote HBV vaccination in patients with no exposure to HBV and to switch 3TC to universal TDF in those with CHB.

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          Most cited references39

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          Molecular identification of hepatitis B virus genotypes/subgenotypes: revised classification hurdles and updated resolutions.

          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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            HIV-HBV coinfection--a global challenge.

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              Reducing the neglected burden of viral hepatitis in Africa: strategies for a global approach.

              The burden of liver disease may dramatically increase in the near future in Africa, where screening and access to care and treatment are hampered by inadequate disease surveillance, lack of high-quality tools to assess chronic liver disease, and underestimated needs for human and financial resources. Chronic hepatitis may be considered as silent and neglected killer, fuelled by many years of global inertia from stakeholders and policy makers alike. However, the global battle against viral hepatitis is facing a new era owing to the advent of highly effective drugs, innovative tools for screening and clinical follow-up, and recent signs that governments, advocacy groups and global health organizations are mobilizing to advocate universal access-to-treatment. This review details the barriers to prevention, screening and treatment of viral hepatitis on the African continent, focuses on the urgent need for operational and research programmes, and suggests integrated ways to tackle the global epidemic.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 January 2016
                2016
                : 11
                : 1
                : e0143869
                Affiliations
                [1 ]Laboratoire de Rétrovirologie, Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon
                [2 ]Unité Mixte de Recherche VIH et Maladies Infectieuses Associées (UMR-VIH-MIA), CIRMF, Libreville, Gabon
                [3 ]Centre de Traitement Ambulatoire (CTA), Franceville, Gabon
                [4 ]Service de Virologie, Centre Pasteur du Cameroun, Yaoundé, Cameroun
                [5 ]Laboratoire de Virologie, AP-HP, Hôpital Saint Louis; INSERM U941, Université Paris Diderot; Laboratoire associé au Centre national de Référence du VIH, Paris, France
                CEA, FRANCE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: FR AMO. Performed the experiments: LD BBM. Analyzed the data: BBM SFS. Contributed reagents/materials/analysis tools: FR AMO SFS. Wrote the paper: BBM SFS AMO FR MAA RN MLC. Recruitment and treatment of patients: JS.

                [¤a]

                Current address: Zoonose et Maladies Emergentes (ZME), CIRMF, Gabon

                [¤b]

                Current address: Unité VIH/Hépatites, Institut Pasteur du Cambodge, Cambodge

                Article
                PONE-D-15-28127
                10.1371/journal.pone.0143869
                4713159
                26764909
                b50fed8c-e8c6-4e8e-8091-b13d948ea118
                © 2016 Bivigou-Mboumba et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 29 June 2015
                : 9 November 2015
                Page count
                Figures: 7, Tables: 2, Pages: 16
                Funding
                The Centre International de Recherches Médicales de Franceville (CIRMF), Gabon, is funded by the Gabonese Government, Total Gabon and the French Foreign Ministry. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                All HBV sequences are now deposited in the databank and we have modified the acknowledgments section of our manuscript accordingly. Due to ethical restrictions for the protection of patient privacy, our data are available upon request to BIVIGOU-MBOUMBA Berthold ( bivigou.berthold@ 123456gmail.com ), and ROUET François ( franrouet@ 123456yahoo.fr ).

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