Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013;8(3):e58236.
doi: 10.1371/journal.pone.0058236. Epub 2013 Mar 4.

Differential Plasma microRNA Profiles in HBeAg Positive and HBeAg Negative Children With Chronic Hepatitis B

Free PMC article

Differential Plasma microRNA Profiles in HBeAg Positive and HBeAg Negative Children With Chronic Hepatitis B

Thilde Nordmann Winther et al. PLoS One. .
Free PMC article


Background and aim: 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.

Patients and 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).

Conclusion: 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.

Conflict of interest statement

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


Figure 1
Figure 1. Levels of 16 identified miRNAs in plasma from HBeAg positive, HBeAg negative, and healthy children.
A panel of 16 miRNAs was identified as significantly differentially expressed in plasma from 34 HBeAg positive, 26 HBeAg negative, and 60 healthy children. All 16 of the identified miRNAs were highly upregulated in plasma from HBeAg positive children compared with levels in plasma from HBeAg negative children. All miRNAs had their lowest expression in healthy children. Results are corrected for age and gender. –ΔCT: −delta cycle threshold. The bars represent geometric means of –ΔCT values ±SEM.
Figure 2
Figure 2. Correlation between circulating miRNAs and HBV DNA.
The relationship between circulating miRNAs and viral load was investigated and a strong positive correlation was found between plasma levels of all 16 miRNAs and HBV DNA. Results are corrected for age, gender, and ALT.

Similar articles

See all similar articles

Cited by 25 articles

See all "Cited by" articles


    1. WHO website (2012) Hepatitis B. World Health Organization fact sheet 204. Available: 2012 Jun 20.
    1. McMahon BJ, Alward WL, Hall DB, Heyward WL, Bender TR, et al. (1985) Acute hepatitis B virus infection: relation of age to the clinical expression of disease and subsequent development of the carrier state. J Infect Dis 151: 599–603. - PubMed
    1. Tassopoulos NC, Papaevangelou GJ, Sjogren MH, Roumeliotou-Karayannis A, Gerin JL, et al. (1987) Natural history of acute hepatitis B surface antigen-positive hepatitis in Greek adults. Gastroenterology 92: 1844–1850. - PubMed
    1. McMahon BJ (2009) The natural history of chronic hepatitis B virus infection. Hepatology 49: S45–55. - PubMed
    1. Lok AS, Heathcote EJ, Hoofnagle JH (2001) Management of hepatitis B: 2000–summary of a workshop. Gastroenterology 120: 1828–1853. - PubMed

Publication types

MeSH terms

Grant support

TNW was the recipient of a PhD scholarship from the Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. CHBB and FP were supported by the Danish Council for Strategic Research (09-067036/DSF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.