Plasma microRNA: A novel non-invasive biomarker for HBV-associated liver fibrosis staging

血浆微RNA:一种用于乙型肝炎病毒相关肝纤维化分期的新型非侵入性生物标志物

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Abstract

The aim of the present study was to evaluate the potential use of 7 plasma miRNAs for liver fibrosis staging in patients with chronic hepatitis B virus (HBV) infection. Relative levels of miRNAs were measured using quantitative polymerase chain reaction and used to develop a diagnostic panel. A receiver operating characteristic (ROC) curve was drawn to evaluate the performance of individual miRNAs and the whole panel. It was identified that hsa-miR-122 exhibited significantly different expression levels between F4 and F3, F2, F1, and F0 fibrosis stages (P<0.05), and between F2 and F1 stages (P=0.045); hsa-miR-146a-5p, hsa-miR-29c-3p and hsa-miR-223 exhibited significantly different expression levels between F4 and F0 stages. ROC analysis revealed that hsa-miR-122-5p, hsa-miR-223 and hsa-miR-29c-3p identified patients with ≥F2 fibrosis with area under the curve (AUC) =0.745, 0.631 and 0.670, respectively. hsa-miR-122-5p identified patients with ≥F3 disease (AUC=0.783). hsa-miR-122-5p, hsa-miR-223 and hsa-miR-29c-3p identified patients with cirrhosis with AUC=0.776, 0.617 and 0.619, respectively. The miRNA panel exhibited a higher accuracy compared with individual miRNAs in discriminating between ≥F2, ≥F3 and F4 fibrosis stages with AUC=0.904, 0.889 and 0.835, respectively. hsa-miR-122-5p, hsa-miR-146a, hsa-miR-29c and hsa-miR-223 were positively correlated with fibrosis stage. hsa-miR-122-5p and hsa-miR-381-3p were negatively correlated with alanine aminotransferase, aspartate transaminase and HBV viral DNA load. These 7 miRNAs may serve as potential biomarkers of liver fibrosis in patients with HBV-associated fibrosis. The miRNA panel may serve as a novel non-invasive method for liver fibrosis staging.

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