title: Differential plasma microRNA profiles in HBeAg positive and HBeAg negative children with chronic hepatitis B.
abstract: OBJECTIVE
  Children chronically infected with hepatitis B virus (HBV) are at high risk of progressive liver disease. However, no treatment is available that is consistently effective in curing chronic hepatitis B (CHB) in children. Improved understanding of the natural course of disease is warranted. Identification of specific microRNA (miRNA) profiles in children chronically infected with HBV may provide insight into the pathogenesis of CHB and lead to advances in the management of children with CHB.
  
  
  METHODS
  MiRNA PCR panels were employed to screen plasma levels of 739 miRNAs in pooled samples from HBeAg positive, HBeAg negative, and healthy children. The three groups' plasma miRNA profiles were compared, and aberrantly expressed miRNAs were identified. The identified miRNAs were then validated. Individual RT-qPCRs were performed on plasma from 34 HBeAg positive, 26 HBeAg negative, and 60 healthy children.
  
  
  RESULTS
  A panel of 16 plasma miRNAs were identified as aberrantly expressed in HBeAg positive and HBeAg negative children (p<0.001). Levels of all of the miRNAs were upregulated in HBeAg positive children compared with in HBeAg negative children. A positive correlation was furthermore found between plasma levels of the identified miRNAs and HBV DNA (p<0.001).
  
  
  CONCLUSIONS
  We are the first to investigate the plasma miRNA profile of children chronically infected with HBV. Our data indicates the existence of a relationship between abundance of circulating miRNAs and immunological stages in the natural course of disease. Certain miRNAs may contribute to the establishment and maintenance of CHB in children. Further studies are warranted to advance understanding of miRNAs in the pathogenesis of CHB, hopefully leading to the identification of future therapeutic targets.
authors.affiliation: Department of Paediatrics, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark. thildewinther@gmail.com
authors.forename: Thilde Nordmann
authors.initials: TN
authors.lastname: Winther
authors.forename: Claus Heiner
authors.initials: CH
authors.lastname: Bang-Berthelsen
authors.forename: Ida Louise
authors.initials: IL
authors.lastname: Heiberg
authors.forename: Flemming
authors.initials: F
authors.lastname: Pociot
authors.forename: Birthe
authors.initials: B
authors.lastname: Hogh
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood* / Q000276:immunology; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood* / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007223:Infant; D008099:Liver / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D035683:MicroRNAs