Blog
About

  • Record: found
  • Abstract: found
  • Article: found
Is Open Access

Identification of novel susceptibility loci associated with hepatitis B surface antigen seroclearance in chronic hepatitis B

Read this article at

Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      Background/Aims

      The seroclearance of hepatitis B virus (HBV) surface antigen (HBsAg) is regarded as a functional cure of chronic hepatitis B (CHB) although it occurs rarely. Recently, several genome-wide association studies (GWASs) revealed various genetic alterations related to the clinical course of HBV infection. However, all of these studies focused on the progression of HBV infection to chronicity and had limited application because of the heterogeneity of HBV genotypes. In the present study, we aimed to determine susceptibility genetic markers for seroclearance of HBsAg in CHB patients with a homogenous viral genotype.

      Methods

      One hundred patients with CHB who had experienced HBsAg seroclearance before 60 years of age and another 100 with CHB showing high serum levels of HBsAg even after 60 years of age were enrolled. Extreme-phenotype GWAS was conducted using blood samples of participants.

      Results

      We identified three single nucleotide polymorphisms, rs7944135 ( P = 4.17 × 10 −6, odds ratio [OR] = 4.16, 95% confidence interval [CI] = 2.27–7.63) at 11q12.1, rs171941 ( P = 3.52×10 −6, OR = 3.69, 95% CI = 2.13–6.42) at 5q14.1, and rs6462008 ( P = 3.40×10 −6, OR = 0.34, 95% CI = 0.22–0.54) at 7p15.2 as novel susceptibility loci associated with HBsAg seroclearance in patients with CHB. The flanking genes at these loci including MPEG1, DTX4, MTX3, and HOXA13 were suggested to have functional significance. In addition, through functional analysis, CXCL13 was also presumed to be related.

      Conclusions

      To the best of our knowledge, this study is the first GWAS regarding the seroclearance of HBsAg in CHB patients. We identify new susceptibility loci for cure of CHB, providing new insights into its pathophysiology.

      Related collections

      Most cited references 44

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      A global reference for human genetic variation

       Lachlan Coin (2016)
      The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.
        Bookmark
        • Record: found
        • Abstract: found
        • Article: not found
        Is Open Access

        Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity.

        Chronic hepatitis B virus infection is one of the most serious infections and a major risk factor for deaths from cirrhosis and liver cancer. We estimate age-, sex- and region-specific prevalence of chronic HBV infection and calculate the absolute number of persons being chronically infected. A systematic review of the literature for studies reporting HBV infection was conducted and worldwide HBsAg seroprevalence data was collected over a 27-year period (1980-2007). Based on observed data, age-specific prevalence and endemicity were estimated on a global level and for all world regions for 1990 and 2005 using an empirical Bayesian hierarchical model. From 1990 to 2005, the prevalence of chronic HBV infection decreased in most regions. This was particularly evident in Central sub-Saharan Africa, Tropical and Central Latin America, South East Asia and Central Europe. Despite this decrease in prevalence, the absolute number of HBsAg positive persons increased from 223 million in 1990 to 240 million in 2005. Age-specific prevalence varied by geographical region with highest endemicity levels in sub-Saharan Africa and prevalence below 2% in regions such as Tropical and Central Latin America, North America and Western Europe. Asian regions showed distinct prevalence patterns with lower intermediate prevalence in South Asia, but up to 8.6% HBsAg prevalence in East Asia. Strong declines were seen in South East Asian children. Declines in HBV infection prevalence may be related to expanded immunization. The increasing overall number of individuals being chronically infected with HBV, and the widespread global differences in HBV prevalence call for targeted approaches to tackle HBV-related mortality and morbidity. HBV infection prevalence data are needed at country and sub-national level to estimate disease burden and guide health and vaccine policy. Copyright © 2012 Elsevier Ltd. All rights reserved.
          Bookmark
          • Record: found
          • Abstract: found
          • Article: not found

          EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection.

          Hepatitis B virus (HBV) infection remains a global public health problem with changing epidemiology due to several factors including vaccination policies and migration. This Clinical Practice Guideline presents updated recommendations for the optimal management of HBV infection. Chronic HBV infection can be classified into five phases: (I) HBeAg-positive chronic infection, (II) HBeAg-positive chronic hepatitis, (III) HBeAg-negative chronic infection, (IV) HBeAg-negative chronic hepatitis and (V) HBsAg-negative phase. All patients with chronic HBV infection are at increased risk of progression to cirrhosis and hepatocellular carcinoma (HCC), depending on host and viral factors. The main goal of therapy is to improve survival and quality of life by preventing disease progression, and consequently HCC development. The induction of long-term suppression of HBV replication represents the main endpoint of current treatment strategies, while HBsAg loss is an optimal endpoint. The typical indication for treatment requires HBV DNA >2,000IU/ml, elevated ALT and/or at least moderate histological lesions, while all cirrhotic patients with detectable HBV DNA should be treated. Additional indications include the prevention of mother to child transmission in pregnant women with high viremia and prevention of HBV reactivation in patients requiring immunosuppression or chemotherapy. The long-term administration of a potent nucleos(t)ide analogue with high barrier to resistance, i.e., entecavir, tenofovir disoproxil or tenofovir alafenamide, represents the treatment of choice. Pegylated interferon-alfa treatment can also be considered in mild to moderate chronic hepatitis B patients. Combination therapies are not generally recommended. All treated and untreated patients should be monitored for treatment response and adherence, and the risk of progression and development of complications. HCC remains the major concern for treated chronic hepatitis B patients. Several subgroups of patients with HBV infection require specific focus. Future treatment strategies to achieve 'cure' of disease and new biomarkers are discussed.
            Bookmark

            Author and article information

            Affiliations
            [1 ] Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
            [2 ] Department of Physiology, Ajou University School of Medicine, Suwon, Korea
            [3 ] Department of Biomedical Science, Graduate School, Ajou University, Suwon, Korea
            [4 ] Department of Computer Science and Engineering, Korea University College of Informatics, Seoul, Korea
            Universita degli Studi di Pisa, ITALY
            Author notes

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

            Contributors
            ORCID: http://orcid.org/0000-0002-7747-4293, Role: Formal analysis, Role: Investigation, Role: Writing – original draft
            Role: Formal analysis, Role: Investigation, Role: Writing – original draft
            Role: Formal analysis, Role: Visualization
            Role: Data curation, Role: Investigation
            Role: Formal analysis
            Role: Formal analysis
            Role: Investigation
            Role: Investigation
            Role: Investigation
            Role: Investigation
            Role: Investigation
            Role: Investigation
            Role: Investigation
            Role: Investigation
            Role: Investigation
            Role: Investigation
            Role: Investigation
            Role: Funding acquisition, Role: Methodology
            Role: Conceptualization, Role: Writing – review & editing
            Role: Editor
            Journal
            PLoS One
            PLoS ONE
            plos
            plosone
            PLoS ONE
            Public Library of Science (San Francisco, CA USA )
            1932-6203
            5 July 2018
            2018
            : 13
            : 7
            29975729 6033413 10.1371/journal.pone.0199094 PONE-D-17-38758
            © 2018 Kim 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.

            Counts
            Figures: 4, Tables: 3, Pages: 15
            Product
            Funding
            Funded by: funder-id http://dx.doi.org/10.13039/501100003725, National Research Foundation of Korea;
            Award ID: NRF-2012R1A5A2048183
            Award Recipient :
            This work was funded in full by the National Research Foundation of Korea (NRF; https://www.nrf.re.kr) funded by the Korea government (MSIP), grant number NRF-2012R1A5A2048183. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
            Categories
            Research Article
            Biology and Life Sciences
            Computational Biology
            Genome Analysis
            Genome-Wide Association Studies
            Biology and Life Sciences
            Genetics
            Genomics
            Genome Analysis
            Genome-Wide Association Studies
            Biology and Life Sciences
            Genetics
            Human Genetics
            Genome-Wide Association Studies
            Medicine and health sciences
            Infectious diseases
            Viral diseases
            Hepatitis
            Hepatitis B
            Medicine and health sciences
            Gastroenterology and hepatology
            Liver diseases
            Infectious hepatitis
            Hepatitis B
            Biology and Life Sciences
            Genetics
            Molecular Genetics
            Biology and Life Sciences
            Molecular Biology
            Molecular Genetics
            Biology and Life Sciences
            Biochemistry
            Proteins
            Interferons
            Biology and Life Sciences
            Genetics
            Genetic Loci
            Biology and life sciences
            Microbiology
            Medical microbiology
            Microbial pathogens
            Viral pathogens
            Hepatitis viruses
            Hepatitis B virus
            Medicine and health sciences
            Pathology and laboratory medicine
            Pathogens
            Microbial pathogens
            Viral pathogens
            Hepatitis viruses
            Hepatitis B virus
            Biology and life sciences
            Organisms
            Viruses
            Viral pathogens
            Hepatitis viruses
            Hepatitis B virus
            Biology and Life Sciences
            Genetics
            Human Genetics
            Biology and Life Sciences
            Genetics
            Heredity
            Genetic Mapping
            Haplotypes
            Custom metadata
            All relevant data are available from figshare: https://figshare.com/articles/gtReport_txt/6614975 (DOI: 10.6084/m9.figshare.6614975).

            Uncategorized

            Comments

            Comment on this article