Abstract
Background and AimChildren 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 MethodsMiRNA 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.ResultsA 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).ConclusionWe 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.
Highlights
Chronic hepatitis B (CHB) is a global health problem, with more than 350 million people chronically infected worldwide [1]
We are the first to investigate the plasma miRNA profile of children chronically infected with hepatitis B virus (HBV)
Children with chronic hepatitis B (CHB) were divided into two groups based on hepatitis B e antigen (HBeAg) status: 34 children were HBeAg positive, and 26 children were HBeAg negative
Summary
Chronic hepatitis B (CHB) is a global health problem, with more than 350 million people chronically infected worldwide [1]. The natural course of CHB is usually characterised by three stages: The immune tolerant, immune active, and immune inactive stages [5,6]. Most children are considered to be in the immune tolerant stage, with a high viral load, measurable hepatitis B e antigen (HBeAg), and minimal elevated alanine aminotransferase (ALT). The immune active stage is characterised by a reduction in HBV DNA levels and increased liver damage. HBeAg seroconversion is usually followed by clinical remission and a lifelong inactive stage, with low viral load and normal ALT level. Children in the inactive phase have a low risk of liver disease progression, but HBV reactivation can occur and trigger immune mediated liver injury [5,6]. Children chronically infected with hepatitis B virus (HBV) are at high risk of progressive liver disease. 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
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