Evaluation of serum MicroRNAs and HCV Core antigen as predictive and diagnostic biomarkers for chronic hepatitis C management in Iraqi patients: comparison with PCR-based detection.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a growing health issue in Iraq, emphasizing the necessity to use precise diagnostic and predictive biomarkers to guide disease management. Although PCR-based detection of HCV viral load is highly sensitive, it is expensive and requires sophisticated facilities. OBJECTIVES: To evaluate the diagnostic accuracy of serum microRNA-122 (miR-122), microRNA-221 (miR-221), and HCV core antigen (HCV core Ag) compared with PCR-based detection of HCV viral load, to determine their predictive value for treatment response, and to monitor their changes during direct-acting antiviral (DAA) therapy. MATERIALS AND METHODS: In this prospective study, 50 treatment-naive patients with chronic hepatitis C (CHC) and 50 healthy controls were recruited from Al-Ramadi Teaching Hospital and affiliated private clinics from January 2025 to December 2025. Each patient was assessed longitudinally at baseline, week 8, and week 12 of Sofosbuvir-Velpatasvir therapy, giving 150 patient-time observations. HCV RNA was measured using the GeneXpert system, HCV core antigen was measured using the Abbott Architect HCV Ag assay, and serum miR-122 and miR-221 were quantified using a separate RT-qPCR platform and normalized to miR-191. RESULTS: Serum miR-122 had excellent diagnostic accuracy (AUC = 0.92), with sensitivity and specificity of 89.3% and 86.0%, respectively. HCV core antigen demonstrated good diagnostic accuracy (AUC = 0.87). A combined model of miR-122 and HCV core antigen yielded superior diagnostic accuracy compared with either marker alone (AUC = 0.95). Baseline composite score predicted EOT virological response with good accuracy (AUC = 0.84). Significant correlations were found between HCV viral load and each of serum miR-122 (r = 0.78) and HCV core antigen (r = 0.82). CONCLUSION: Serum miR-122 and HCV core antigen are clinically relevant complementary biomarkers for the diagnosis of chronic hepatitis C and for predicting on-treatment virological response in Iraqi patients. Although the microRNAs are themselves quantified by RT-qPCR, these findings support wider implementation of miRNA- and HCV core antigen-based testing as lower-cost complements, and in the case of HCV core antigen a potential alternative, to HCV RNA PCR for diagnosis and treatment monitoring in resource-constrained settings.