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Circulating MicroRNAs in Plasma of Hepatitis B e Antigen Positive Children Reveal Liver-Specific Target Genes

DOI: 10.1155/2014/791045

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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. 1. Introduction Children with chronic hepatitis B (CHB) have a lifetime risk of developing hepatocellular carcinoma (HCC) up to 25% and an incidence of cirrhosis of 2-3% per year [1, 2]. It is widely accepted that the natural course of CHB is determined by the host-virus interaction; however, the exact mechanisms responsible for disease progression in children are not fully understood. Evidence suggests that microRNAs play a role in the complex interaction between the hepatitis B virus and host [3]. Our group recently identified a panel of 16 microRNAs aberrantly expressed in plasma of children with CHB and suggested a potential role of these microRNAs in the pathogenesis of childhood CHB [4]. Risk of progressive liver disease primarily applies to hepatitis B e antigen positive (HBeAg-positive) children and seroclearance of HBeAg is a key event in the natural course of disease [5]. Most children who undergo HBeAg seroconversion are defined inactive carriers, with absent or low viral replication, and usually inactive liver histology [5]. Inactive carriers with no signs of cirrhosis at seroconversion do

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