title: Circulating MicroRNAs in Plasma of Hepatitis B e Antigen Positive Children Reveal Liver-Specific Target Genes.
abstract: Background and Aim. Hepatitis B e antigen positive (HBeAg-positive) children are at high risk of severe complications such as hepatocellular carcinoma and cirrhosis. Liver damage is caused by the host immune response to infected hepatocytes, and we hypothesise that specific microRNAs play a role in this complex interaction between virus and host. The study aimed to identify microRNAs with aberrant plasma expressions in HBeAg-positive children and with liver-specific target genes. Methods. By revisiting our previous screen of microRNA plasma levels in HBeAg-positive and HBeAg-negative children with chronic hepatitis B (CHB) and in healthy controls, candidate microRNAs with aberrant plasma expressions in HBeAg-positive children were identified. MicroRNAs targeting liver-specific genes were selected based on bioinformatics analysis and validated by qRT-PCR using plasma samples from 34 HBeAg-positive, 26 HBeAg-negative, and 60 healthy control children. Results. Thirteen microRNAs showed aberrant plasma expressions in HBeAg-positive children and targeted liver-specific genes. In particular, three microRNAs were upregulated and one was downregulated in HBeAg-positive children compared to HBeAg-negative and healthy control children, which showed equal levels. Conclusion. The identified microRNAs might impact the progression of CHB in children. Functional studies are warranted, however, to elucidate the microRNAs' role in the immunopathogenesis of childhood CHB.
authors.affiliation: Department of Paediatrics, Hvidovre Hospital, University of Copenhagen, Kettegaard Allé 30, 2650 Hvidovre, Denmark ; Department of Paediatrics and Center for Non-Coding RNA in Technology and Health, Herlev Hospital, University of Copenhagen, Arkaden, 2730 Herlev, Denmark.
authors.forename: Thilde Nordmann
authors.initials: TN
authors.lastname: Winther
authors.affiliation: Department of Paediatrics, Hvidovre Hospital, University of Copenhagen, Kettegaard Allé 30, 2650 Hvidovre, Denmark ; Department of Paediatrics and Center for Non-Coding RNA in Technology and Health, Herlev Hospital, University of Copenhagen, Arkaden, 2730 Herlev, Denmark.
authors.forename: Kari Stougaard
authors.initials: KS
authors.lastname: Jacobsen
authors.affiliation: Department of Paediatrics and Center for Non-Coding RNA in Technology and Health, Herlev Hospital, University of Copenhagen, Arkaden, 2730 Herlev, Denmark.
authors.forename: Aashiq Hussain
authors.initials: AH
authors.lastname: Mirza
authors.affiliation: Department of Paediatrics, Hvidovre Hospital, University of Copenhagen, Kettegaard Allé 30, 2650 Hvidovre, Denmark.
authors.forename: Ida Louise
authors.initials: IL
authors.lastname: Heiberg
authors.affiliation: Department of Paediatrics and Center for Non-Coding RNA in Technology and Health, Herlev Hospital, University of Copenhagen, Arkaden, 2730 Herlev, Denmark.
authors.forename: Claus Heiner
authors.initials: CH
authors.lastname: Bang-Berthelsen
authors.affiliation: Department of Paediatrics and Center for Non-Coding RNA in Technology and Health, Herlev Hospital, University of Copenhagen, Arkaden, 2730 Herlev, Denmark.
authors.forename: Flemming
authors.initials: F
authors.lastname: Pociot
authors.affiliation: Department of Paediatrics, Hvidovre Hospital, University of Copenhagen, Kettegaard Allé 30, 2650 Hvidovre, Denmark.
authors.forename: Birthe
authors.initials: B
authors.lastname: Hogh