Abstract
Circulating microRNAs have been investigated as markers of disease severity in a variety of conditions. We examined whether circulating miR-21 and miR-29a could serve as markers of hepatic fibrosis and disease etiology in children with various liver diseases. Circulating miR-21 and miR-29a were determined in 58 children (21 female, age 0.1–17.8 (median 9.8) years)) with chronic liver disease and compared to histological grading of hepatic fibrosis. 22 healthy children served as controls for circulating miRNAs. Levels of circulating miR-21 appeared to be age-dependent in healthy children. Children with biliary atresia had significantly higher levels of miR-21 compared both to healthy controls and to age-matched children with other cholestatic liver disease. Circulating miR-29a levels in biliary atresia children did not differ from healthy controls, but tended to be higher than in age-matched children with other cholestatic liver disease. Neither miR-21 nor miR-29a correlated well with hepatic fibrosis. Circulating miR-21 and miR-29a levels can potentially serve as non-invasive diagnostic markers to differentiate biliary atresia from other cholestatic disease in infancy. They do not appear suitable as non-invasive markers for the degree of hepatic fibrosis in an unselected cohort of children with various liver diseases. The discriminating effect regarding neonatal cholestasis should be followed up in a prospective longitudinal study.
Highlights
MicroRNAs are small (18–23 nucleotides), non-coding RNA molecules involved in regulation and stabilization of mRNA translation [1] that have been shown to play a pathogenetic role in several disease entities [2,3,4]
Ourfirst firstquestion question was whether circulating miR‐21 and miR‐29a couldas serve as a of marker fibrosis, independent of disease etiology
Circulating miR-21 levels are higher in infants with biliary atresia compared to healthy children and age-matched patients with other cholestatic disease
Summary
MicroRNAs are small (18–23 nucleotides), non-coding RNA molecules involved in regulation and stabilization of mRNA translation [1] that have been shown to play a pathogenetic role in several disease entities [2,3,4]. Crohn’s disease [6] and hepatocellular carcinoma (HCC) [4]. MicroRNAs have been extensively investigated in the context of non-alcoholic fatty liver disease and HCC [4]. Knowledge on microRNA differential regulation in pediatric liver disease is still scarce. MicroRNAs have been investigated as potential markers of acetaminophen-toxicity in children [7]. MiR-122, miR-25, and miR-21 were recently described as potential markers of cystic-fibrosis-related liver disease in children [8].
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