Abstract
Background
Plasma microRNA (miRNA) levels may be altered during pathological processes; therefore, they may potentially serve as biomarkers for the diagnosis and prognosis of human diseases. This study aimed to explore whether plasma miRNAs may serve as new biomarkers for liver injury among chronic hepatitis B (CHB) patients with normal or nearly normal alanine aminotransferase (ALT) levels.
Methods
Plasma miRNAs from each of three independent groups (no prominent liver injury and persistently normal ALT levels, NPNALT; significant liver injury with persistently normal ALT levels, SPNALT; and healthy) were profiled by miRNA microarray analysis. Differentially expressed miRNAs were then validated by a quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. The area under the receiver operating characteristic (AUC) curve was used to analyze the candidate miRNAs validated by qRT-PCR for diagnostic accuracy.
Results
Twenty differentially expressed miRNAs were identified by microarray analysis. Seven miRNAs with elevated serum levels were validated by qRT-PCR analysis, and four of them were significantly different between the SPNALT and NPNALT groups. The AUCs of hsa-miR-122-5p and hsa-miR-151-3p were 0.877 (cutoff value = 13.38; 95% CI 0.792–0.963; sensitivity = 83.3%, specificity = 80%) and 0.882 (cutoff value = 7.4; 95% CI 0.797–0.966; sensitivity = 83.3%, specificity = 73.3%), respectively, indicating early liver injury. However, there was no significant correlation of miRNAs with either necroinflammation or fibrosis.
Conclusion
Serum hsa-miR-122-5p and hsa-miR-151-3p may function as new biomarkers for liver injury in SPNALT patients. With these two biomarkers, we may be able to identify a subset of patients who are experiencing liver injury but have normal ALT levels for further evaluation with a biopsy procedure.
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Acknowledgements
This study was supported by grants from the National Science and Technology Major Project (2012ZX10002004-001) and the Science Fund for Creative Research Groups of the National Natural Science Foundation of China (No. 81121002).
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Jin-Lin Cheng, Hong Zhao, Shi-Gui Yang, Er-Mei Chen, Wen-Qian Chen, Lan-Juan Li declare that they have no conflicts of interest.
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This was a prospective study conducted at the First Affiliated Hospital, Medical College of Zhejiang University. The study protocol was reviewed and approved by the Ethics Committee of the First Affiliated Hospital, Medical College of Zhejiang University, and all experiments were carried out in accordance with the relevant guidelines and regulations.
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Cheng, JL., Zhao, H., Yang, SG. et al. Plasma miRNA-122-5p and miRNA-151a-3p identified as potential biomarkers for liver injury among CHB patients with PNALT. Hepatol Int 12, 277–287 (2018). https://doi.org/10.1007/s12072-018-9871-0
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DOI: https://doi.org/10.1007/s12072-018-9871-0