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Differential plasma microRNA profiles in HBeAg positive and HBeAg negative children with chronic hepatitis B
Thilde Nordmann Winther1, Claus Heiner Bang-Berthelsen, Ida Louise Heiberg
1Department of Paediatrics, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark. thildewinther@gmail.com
Insights
Hepatitis B virus (HBV) infection in children shows distinct microRNA (miRNA) profiles. Upregulated plasma miRNAs correlate with HBV DNA levels, offering insights into chronic hepatitis B (CHB) pathogenesis.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
- Pediatrics
Background:
- Children with chronic hepatitis B virus (HBV) infection face a high risk of progressive liver disease.
- Current treatments for chronic hepatitis B (CHB) in children lack consistent efficacy for a cure.
- Understanding the natural disease course and pathogenesis is crucial for improved management.
Purpose of the Study:
- To identify specific microRNA (miRNA) profiles in children with chronic HBV infection.
- To investigate the potential role of miRNAs in the pathogenesis of CHB in pediatric populations.
- To explore miRNAs as potential biomarkers and therapeutic targets for CHB in children.
Main Methods:
- Screening of 739 plasma miRNAs using PCR panels in pooled samples from HBeAg positive, HBeAg negative, and healthy children.
- Comparison of plasma miRNA profiles to identify aberrantly expressed miRNAs.
- Validation of identified miRNAs through individual RT-qPCR in a cohort of 34 HBeAg positive, 26 HBeAg negative, and 60 healthy children.
Main Results:
- A panel of 16 plasma miRNAs were found to be significantly aberrantly expressed in children with CHB (p<0.001).
- All identified miRNAs showed upregulation in HBeAg positive children compared to HBeAg negative children.
- A positive correlation was observed between plasma miRNA levels and HBV DNA levels (p<0.001).
Conclusions:
- This study is the first to investigate plasma miRNA profiles in children with chronic HBV infection.
- Circulating miRNA abundance is linked to immunological stages in the natural history of CHB.
- Specific miRNAs may play a role in the establishment and persistence of CHB in children, warranting further investigation for therapeutic targets.
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.
