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      Different evolutionary dynamics of hepatitis B virus genotypes A and D, and hepatitis D virus genotypes 1 and 2 in an endemic area of Yakutia, Russia

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          Abstract

          Background

          The geographic distribution of the hepatitis B virus (HBV) and the hepatitis D virus (HDV) genotypes is uneven. We reconstructed the temporal evolution of HBV and HDV in Yakutia, one of the regions of Russia most affected by HBV and HDV, in an attempt to understand the possible mechanisms that led to unusual for Russia pattern of viral genotypes and to identify current distribution trends.

          Methods

          HBV and HDV genotypes were determined in sera collected in 2018–2019 in Yakutia from randomly selected 140 patients with HBV monoinfection and 59 patients with HBV/HDV. Total 86 HBV and 88 HDV genomic sequences isolated in Yakutia between 1997 and 2019 were subjected to phylodynamic and philogeographic Bayesian analysis using BEAST v1.10.4 software package. Bayesian SkyGrid reconstruction and Birth–Death Skyline analysis were applied to estimate HBV and HDV population dynamics.

          Results

          Currently, HBV-A and HDV-D genotypes are prevalent in Yakutia, in both monoinfected and HDV-coinfected patients. Bayesian analysis has shown that the high prevalence of HBV-A in Yakutia, which is not typical for Russia, initially emerged after the genotype was introduced from Eastern Europe in the fifteenth century (around 600 (95% HPD: 50–715) years ago). The acute hepatitis B epidemics in the 1990s in Yakutia were largely associated with this particular genotype, as indicated by temporal changes in HBV-A population dynamics. HBV-D had a longer history in Yakutia and demonstrated stable population dynamics, indicating ongoing viral circulation despite vaccination. No correlation between HBV and HDV genotypes was observed for coinfected patients in Yakutia (r = − 0.016069332). HDV-2b circulates in Russia in Yakutia only and resulted from a single wave of introduction from Central Asia 135 years ago (95% HPD: 60–350 years), while HDV-1 strains resulted from multiple introductions from Europe, the Middle East, Central Asia, and different parts of Russia starting 180 years ago (95% HPD: 150–210 years) and continuing to the present day. The population dynamics of HDV-1 and HDV-2 show no signs of decline despite 20 years of HBV vaccination. The Birth–Death Skyline analysis showed an increase in the viral population in recent years for both HDV genotypes, indicating ongoing HDV epidemics.

          Conclusions

          Taken together, these data call for strict control of HBV vaccination quality and coverage, and implementation of HBV and HDV screening programs in Yakutia.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12879-022-07444-w.

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          Most cited references36

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          MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets.

          We present the latest version of the Molecular Evolutionary Genetics Analysis (Mega) software, which contains many sophisticated methods and tools for phylogenomics and phylomedicine. In this major upgrade, Mega has been optimized for use on 64-bit computing systems for analyzing larger datasets. Researchers can now explore and analyze tens of thousands of sequences in Mega The new version also provides an advanced wizard for building timetrees and includes a new functionality to automatically predict gene duplication events in gene family trees. The 64-bit Mega is made available in two interfaces: graphical and command line. The graphical user interface (GUI) is a native Microsoft Windows application that can also be used on Mac OS X. The command line Mega is available as native applications for Windows, Linux, and Mac OS X. They are intended for use in high-throughput and scripted analysis. Both versions are available from www.megasoftware.net free of charge.
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            The global prevalence of hepatitis D virus infection: Systematic review and meta-analysis

            Background and Aims There are uncertainties about the epidemic patterns of HDV infection and its contribution to the burden of liver disease. We estimated the global prevalence of HDV infection and explored its contribution to the development of cirrhosis and hepatocellular carcinoma (HCC) among HBsAg-positive people. Methods We searched Pubmed, EMBASE and Scopus for studies reporting on total or IgG anti-HDV among HBsAg-positive people. Anti-HDV prevalence was estimated using a binomial mixed model, weighting for study quality and population size. The population attributable fraction (PAF) of HDV to cirrhosis and HCC among HBsAg-positive people was estimated using random effects models. Results We included 282 studies, comprising 376 population samples from 95 countries, which together tested 120,293 HBsAg-positive people for anti-HDV. The estimated anti-HDV prevalence was 4.5% (95% CI 3.6–5.7) among all HBsAg-positive people and 16.4% (14.6–18.6) among those attending hepatology clinics. Worldwide, 0.16% (0.11–0.25) of the general population, totalling 12.0 (8.7–18.7) million people, were estimated to be anti-HDV positive. Prevalence among HBsAg-positive people was highest in Mongolia, the Republic of Moldova and countries in Western and Middle Africa, and was higher in injecting drug users, haemodialysis recipients, men who have sex with men, commercial sex workers, and those with HCV or HIV. Among HBsAg-positive people, preliminary PAF estimates of HDV were 18% (10–26) for cirrhosis and 20% (8–33) for HCC. Conclusions An estimated 12 million people worldwide have experienced HDV infection, with higher prevalence in certain geographic areas and populations. HDV is a significant contributor to HBV-associated liver disease. More quality data are needed to improve the precision of burden estimates. Lay summary We combined all available studies to estimate how many people with hepatitis B also have hepatitis D, a viral infection that only affects people with hepatitis B. About 1 in 22 people with hepatitis B also have hepatitis D, increasing to 1 in 6 when considering people with liver disease. Hepatitis D may cause about 1 in 6 of the cases of cirrhosis and 1 in 5 of the cases of liver cancer that occur in people with hepatitis B. Hepatitis D is an important contributor to the global burden of liver disease.
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              The hepatitis delta virus: Replication and pathogenesis.

              Hepatitis delta virus (HDV) is a defective virus and a satellite of the hepatitis B virus (HBV). Its RNA genome is unique among animal viruses, but it shares common features with some plant viroids, including a replication mechanism that uses a host RNA polymerase. In infected cells, HDV genome replication and formation of a nucleocapsid-like ribonucleoprotein (RNP) are independent of HBV. But the RNP cannot exit, and therefore propagate, in the absence of HBV, as the latter supplies the propagation mechanism, from coating the HDV RNP with the HBV envelope proteins for cell egress to delivery of the HDV virions to the human hepatocyte target. HDV is therefore an obligate satellite of HBV; it infects humans either concomitantly with HBV or after HBV infection. HDV affects an estimated 15 to 20 million individuals worldwide, and the clinical significance of HDV infection is more severe forms of viral hepatitis--acute or chronic--, and a higher risk of developing cirrhosis and hepatocellular carcinoma in comparison to HBV monoinfection. This review covers molecular aspects of HDV replication cycle, including its interaction with the helper HBV and the pathogenesis of infection in humans.
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                Author and article information

                Contributors
                karen-kyuregyan@yandex.ru
                Journal
                BMC Infect Dis
                BMC Infect Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                12 May 2022
                12 May 2022
                2022
                : 22
                : 452
                Affiliations
                [1 ]GRID grid.465497.d, Department of Viral Hepatitis, , Russian Medical Academy of Continuous Professional Education, ; Moscow, Russia 125993
                [2 ]GRID grid.419647.9, Laboratory of Viral Hepatitis, , Mechnikov Research Institute of Vaccines and Sera, ; Moscow, Russia 105064
                [3 ]GRID grid.77642.30, ISNI 0000 0004 0645 517X, Scientific and Educational Resource Center for High-Performance Methods of Genomic Analysis, , Peoples’ Friendship University of Russia (RUDN University), ; Moscow, Russia 117198
                [4 ]JSC «Vector-Best», Research and Production Area, building 36, Koltsovo, Novosibirsk region Russia 630559
                [5 ]N.F. Gamaleya National Research Center for Epidemiology and Microbiology, Ivanovsky Institute of Virology, Ministry of Health of the Russian Federation, Moscow, Russia 123098
                [6 ]GRID grid.440700.7, ISNI 0000 0004 0556 741X, Medical Institute, , M.K. Ammosov North-Eastern Federal University, ; Yakutsk, Russia 677010
                [7 ]The Sakha Republic (Yakutia) Regional Department of Rospotrebnadzor, Yakutsk, Russia 677027
                [8 ]GRID grid.445984.0, ISNI 0000 0001 2224 0652, Medical Faculty, , Belgorod State National Research University, ; Belgorod, Russia 308015
                Article
                7444
                10.1186/s12879-022-07444-w
                9097355
                35550023
                5a45bf64-1c57-4423-a09f-72f837b07499
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.

                History
                : 11 February 2022
                : 29 April 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100006769, Russian Science Foundation;
                Award ID: ID-20-15-00148
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Infectious disease & Microbiology
                hepatitis b virus,hepatitis delta virus,viral genotypes,vaccination,phylodynamics,evolutionary dynamics

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