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      Molecular epidemiology of hepatitis B virus infection in Norway

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          Abstract

          Background

          Hepatitis B virus (HBV) infection remains a serious global health challenge. The widespread distribution of HBV is highlighted by multiple HBV genotypes associated with different geographical origin and transmission patterns, as well as, clinical outcomes. Investigating population HBV genotype composition and origin is therefore highly warranted.

          Methods

          In this molecular epidemiological study we analysed 1157 HBV S-gene sequences collected from patients in Norway, primarily in the period 2004–2011, and linked them to epidemiological data from the Norwegian surveillance system for communicable diseases.

          Results

          Of the patients with reported country of infection ( n = 909), 10% ( n = 93) were infected in Norway, but the majority ( n = 816; 90%) stated that they became infected outside of Norway. Of the patients infected outside of Norway, most became infected in Southeast and East Asia ( n = 465; 51%) and Central, West, and North Africa ( n = 254; 28%). The distribution of HBV genotypes in Norway is dominated by genotype D (32%) followed by genotype A (22%), B and C (18 and 18%, respectively), and E (7%). Genotype B, C and E were phylogenetically categorized by a majority of sequences originating from distinct geographical regions, either Asia or Africa, whereas genotype A and D originated from multiple geographic regions. However, within genotype A and D, our molecular epidemiology analysis indicated a geographical clustering of sequences depending on their geographical origin.

          Conclusions

          The majority of HBV patients in Norway became infected outside of Norway and were represented by most common genotypes. Patients stated to have been infected in Norway were found primarily within genotype A and D, and were phylogenetically characterized by both small local clusters and interspersed sequences that clustered with non-Norwegian sequences, indicating that a proportion of the patients assumed to have been infected in Norway likely became infected outside of Norway although assumed the contrary.

          Electronic supplementary material

          The online version of this article (10.1186/s12879-019-3868-8) contains supplementary material, which is available to authorized users.

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          Most cited references15

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          Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes.

          Sequences of 234 complete genomes and 631 hepatitis B surface antigen genes were used to assess the worldwide diversity of hepatitis B virus (HBV). Apart from the described two subgenotypes each for A and F, also B, C, and D divided into four subgenotypes each in the analysis of complete genomes supported by significant bootstrap values. The subgenotypes of B and C differed in their geographical distribution, with B1 dominating in Japan, B2 in China and Vietnam, B3 confined to Indonesia, and B4 confined to Vietnam, all strains specifying subtype ayw1. Subgenotype C1 was common in Japan, Korea, and China; C2 in China, South-East Asia, and Bangladesh, and C3 in the Oceania comprising strains specifying adrq-, and C4 specifying ayw3 is encountered in Aborigines from Australia. This pattern of defined geographical distribution was less evident for D1-D4, where the subgenotypes were widely spread in Europe, Africa, and Asia, possibly due to their divergence having occurred a longer time ago than for genotypes B and C, with D4 being the first split and still the dominating subgenotype of D in the Oceania. The genetic diversity of HBV and the geographical distribution of its subgenotypes provide a tool to reconstruct the evolutionary history of HBV and may help to complement genetic data in the understanding of the evolution and past migrations of man. 2004 S. Karger AG, Basel.
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            Hepatitis B virus taxonomy and hepatitis B virus genotypes.

            Hepatitis B virus (HBV) is a member of the hepadnavirus family. Hepadnaviruses can be found in both mammals (orthohepadnaviruses) and birds (avihepadnaviruses). The genetic variability of HBV is very high. There are eight genotypes of HBV and three clades of HBV isolates from apes that appear to be additional genotypes of HBV. Most genotypes are now divided into subgenotypes with distinct virological and epidemiological properties. In addition, recombination among HBV genotypes increases the variability of HBV. This review summarises current knowledge of the epidemiology of genetic variability in hepadnaviruses and, due to rapid progress in the field, updates several recent reviews on HBV genotypes and subgenotypes.
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              Hepatitis B virus genotypes and variants.

              At least 10 hepatitis B virus (HBV) genotypes (A to J) with distinct geographic distributions and several HBV mutants, including precore/core promoter mutations and pre-S/S deletion mutations, have been recognized to be not only predictive of liver disease progression but also associated with response to antiviral therapy. HBV genotype-specific pathogenesis may contribute to heterogeneous clinical outcomes in chronic hepatitis B patients across the world. For example, patients with HBV genotypes C and D infection have a lower rate of spontaneous HBeAg seroconversion. In addition, HBV genotypes C and D have a higher frequency of core promoter and pre-S mutations than genotypes A and B. Genotypes C and D also carry a higher lifetime risk of cirrhosis and HCC development than genotypes A and B. Core promoter and pre-S mutations also correlate with an increased risk of hepatocellular carcinoma (HCC). Therapeutically, genotypes A and B patients have a better response to interferon-based therapy than genotypes C and D patients, but the response to nucleos(t)ide analogs is comparable across different HBV genotypes. In conclusion, HBV genotypes and variants may serve as viral genetic markers to predict disease progression as well as help practicing physicians optimize individualized antiviral therapy in clinical practice.
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                Author and article information

                Contributors
                john.pettersson@gmail.com
                Solveig.Myking@fhi.no
                Hilde.Elshaug@fhi.no
                KirstenIreneEge.Bygdas@fhi.no
                Kathrine.Stene-Johansen@fhi.no
                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                7 March 2019
                7 March 2019
                2019
                : 19
                : 236
                Affiliations
                [1 ]ISNI 0000 0001 1541 4204, GRID grid.418193.6, Department of Infectious Disease Epidemiology and Modelling, , Norwegian Institute of Public Health, ; Oslo, Norway
                [2 ]ISNI 0000 0004 1936 9457, GRID grid.8993.b, Zoonosis Science Center, Department of Medical Biochemistry and Microbiology, , Uppsala University, ; Uppsala, Sweden
                [3 ]ISNI 0000 0004 1936 834X, GRID grid.1013.3, Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, , the University of Sydney, ; Sydney, NSW 2006 Australia
                [4 ]ISNI 0000 0000 9580 3113, GRID grid.419734.c, Public Health Agency of Sweden, ; Nobels väg 18, SE-171 82 Solna, Sweden
                [5 ]ISNI 0000 0001 1541 4204, GRID grid.418193.6, Department of Infectious Disease Registries, , Norwegian Institute of Public Health, ; Oslo, Norway
                [6 ]ISNI 0000 0001 1541 4204, GRID grid.418193.6, Department of Molecular Biology, , Norwegian Institute of Public Health, ; Oslo, Norway
                [7 ]ISNI 0000 0001 1541 4204, GRID grid.418193.6, Department of Virology, , Norwegian Institute of Public Health, ; Oslo, Norway
                Author information
                http://orcid.org/0000-0001-6665-7492
                Article
                3868
                10.1186/s12879-019-3868-8
                6407267
                30845915
                3115be1a-b08f-4176-920c-bfb036bff83a
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 16 November 2018
                : 4 March 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001862, Svenska Forskningsrådet Formas;
                Award ID: 2015-710
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Infectious disease & Microbiology
                hepatitis b virus,molecular epidemiology,phylogenetics,genotyping

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