Circulatory microRNAs (miR-16 and miR-885) as Potential Diagnostic Markers for Acute Hepatitis C
Abstract:
Background: The injunctive potential of circulating microRNAs (miRNAs) has raised intense investigation for their use as noninvasive biomarkers for liver diseases, especially for hepatitis C (HC). Objective: To determine the diagnostic accuracy of circulating miR-16 and miR-885 in acute hepatitis C (AHC) patients compared with healthy controls.
Methods: A case–control study was carried out among 120 confirmed cases of acute hepatitis C to compare them with 40 age- and sex-matched healthy controls at Al-Najaf Teaching Hospital, Najaf, Iraq, from March 2024 to February 2025. Concentrations of liver enzymes (ALT, AST, ALP) and C-reactive protein (CRP) in serum were measured using standard biochemical assays, and circulating miR-16 and miR-885 concentrations were measured by quantitative real-time PCR (qRT-PCR).
Results: miR-16 and miR-885 were significantly increased in patients with HC compared to controls (p < 0.001). Compared with miR-16, miR-885 had a higher r value and significance as a positive correlation with ALT (r = 0.71, p < 0.001) and CRP (r = 0.68, p < 0.001). ROC analysis showed good diagnostic accuracy for both biomarkers: the area under the curve (AUC) was 0.798 (p = 0.03) for miR-16 and 0.885 (p < 0.02) for miR-885. Using cut-off points of 1.85 and 2.10 for high/low miR levels, miR-16 had 82.5% sensitivity and 76% specificity, while miR-885 had 88.3% sensitivity and 82.5% specificity.
Conclusion: miR-16 and miR-885 are significantly elevated in acute hepatitis C and correlate strongly with biochemical markers of hepatic injury and inflammation. Notably, miR-885 reflects an excellent accuracy in diagnosis which may provide evidence for our results to support the use of miR-885 as a non-invasive biomarker suitable for the early diagnosis and clinical monitoring of HCV infection.
KeyWords:
Circulatory microRNAs, miR-16, miR-885, Acute Hepatitis C.
References:
- Ariyachet, C., Nokkeaw, A., & Tangkijvanich, P. (2025). MicroRNA-885-5p regulates cell cycle progression in liver cancer cells. International Journal of Molecular Medicine, 56(5), 167. https://doi.org/10.3892/ijmm.2025.5608
- Bandiera, S., Pernot, S., El Saghire, H., Durand, S. C., Thumann, C., Crouchet, E., Ye, T., Fofana, I., Oudot, M. A., Barths, J., Schuster, C., Pessaux, P., Heim, M. H., Baumert, T. F., & Zeisel, M. B. (2016). Hepatitis C Virus-Induced Upregulation of MicroRNA miR-146a-5p in Hepatocytes Promotes Viral Infection and Deregulates Metabolic Pathways Associated with Liver Disease Pathogenesis. Journal of virology, 90(14), 6387–6400. https://doi.org/10.1128/JVI.00619-16
- Fang, Y., Yan, D., Wang, L., Zhang, J., & He, Q. (2022). Circulating microRNAs (miR-16, miR-22, miR-122) expression and early diagnosis of hepatocellular carcinoma. Journal of clinical laboratory analysis, 36(7), e24541. https://doi.org/10.1002/jcla.24541
- Fasano, M., Ieva, F., Ciarallo, M., Caccianotti, B., & Santantonio, T. A. (2024). Acute Hepatitis C: Current Status and Future Perspectives. Viruses, 16(11), 1739. https://doi.org/10.3390/v16111739
- Gui, J., Tian, Y., Wen, X., Zhang, W., Zhang, P., Gao, J., Run, W., Tian, L., Jia, X., & Gao, Y. (2011). Serum microRNA characterization identifies miR-885-5p as a potential marker for detecting liver pathologies. Clinical science (London, England : 1979), 120(5), 183–193. https://doi.org/10.1042/CS20100297
- Huang, Y., Chen, Y., Tu, S., Zhang, J., Qiu, Y., & Yu, W. (2022). Diagnostic accuracy of circulating microRNAs for hepatitis C virus‐associated hepatocellular carcinoma: A systematic review and meta‐analysis. BMC Infectious Diseases, 22, 323. https://doi.org/10.1186/s12879-022-07292-8
- Joshi, N., Chandane Tak, M., & Mukherjee, A. (2022). The involvement of microRNAs in HCV and HIV infection. Therapeutic Advances in Vaccines and Immunotherapy, 10, 1-15. https://doi.org/10.1177/25151355221106104
- Krupa, R., et al. (2021). MicroRNA profile and iron-related gene expression in hepatitis Krupa, R., Malecki, W., Czarny, P., Strycharz, J., Jablkowski, M., Kordek, R., Szemraj, J., & Sliwinski, T. (2019). MicroRNA profile and iron-related gene expression in hepatitis C-related hepatocellular carcinoma: a preliminary study. Archives of medical science : AMS, 17(5), 1175–1183. https://doi.org/10.5114/aoms.2019.86613
- Li, H.-C., et al. (2022). Roles of microRNAs in hepatitis C virus replication and pathogenesis. Viruses, 14(8), 1776. https://doi.org/10.3390/v14081776
- Manzoor, S., Malik, I. R., Jahan, S., Sarwar, M. B., Bashir, A., Shams, S., & Hussain, A. (2023). Serum MicroRNAs as Predictors for HCV Progression and Response to Treatment in Pakistani Patients. Genes, 14(2), 441. https://doi.org/10.3390/genes14020441
- McGowan, K., Simpson, K. J., & Petrik, J. (2020). Expression Profiles of Exosomal MicroRNAs from HEV- and HCV-Infected Blood Donors and Patients: A Pilot Study. Viruses, 12(8), 833. https://doi.org/10.3390/v12080833
- Mokhtari, F., Mohebbi, S. R., Sharifian, A., Ramandi, M., & Razzaghi, M. R. (2021). Circulating non-coding RNAs as potential diagnostic biomarkers in liver diseases. Gastroenterology and hepatology from bed to bench, 14(Suppl1), S10–S23
- Nasser, M. Z., Zayed, N. A., Mohamed, A. M., Attia, D., Esmat, G., & Khairy, A. (2019). Circulating microRNAs (miR-21, miR-223, miR-885-5p) along the clinical spectrum of HCV-related chronic liver disease in Egyptian patients. Arab Journal of Gastroenterology, 20, 198–204. https://doi.org/10.1016/j.ajg.2019.11.003
- Shrivastava, S., Steele, R., Ray, R., & Ray, R. B. (2015). MicroRNAs: Role in Hepatitis C Virus pathogenesis. Genes & diseases, 2(1), 35–45. https://doi.org/10.1016/j.gendis.2015.01.001
- Woo, J. (2024). Biomarkers in detection of hepatitis C virus infection. Pathogens, 13(4), 331. https://doi.org/10.3390/pathogens1304033
- Zhu, B., Wei, X. X., Wang, T. B., Zhou, Y. C., Liu, A. M., & Zhang, G. W. (2015). Increased miR-16 expression induced by hepatitis C virus infection promotes liver fibrosis through downregulation of hepatocyte growth factor and Smad7. Archives of virology, 160(8), 2043–2050. https://doi.org/10.1007/s00705-015-2474-3