Defensins (HAD-1/HBD-1) as novel immune biomarkers in chronic hepatitis C: Association with inflammatory and antiviral cytokines and ROC-based diagnostic accuracy.

Abstract

Chronic hepatitis C virus (HCV) infection is associated with prolonged immune activation and systemic inflammation, which may be reflected in circulating immune mediators. Defensins and cytokines have emerged as potential biomarkers for monitoring immune dysregulation in chronic viral hepatitis. This study aimed to monitoring serum levels of human α-defensin-1 (HAD-1) and human β-defensin-1 (HBD-1) with selected cytokines (IL-6, IL-28, TNF-α, and IFN-) in Iraqi patients with chronic HCV and to evaluate their diagnostic performance by the receiver operating characteristic (ROC) analysis. This cross-sectional case-control study was conducted in Iraq during February-November 2025. It included 100 laboratory-confirmed chronic HCV patients and 50 normal controls. Serum HAD-1, HBD-1, IL-6, IL-28, TNF-α, and IFN- were measured by ELISA. Hematological indices and liver function markers were also analyzed. HCV patients showed significantly increased HAD-1 and HBD-1 levels compared with controls (p< 0.01). Cytokine profiling revealed markedly elevated IL-6, IL-28, TNF-α, and IFN- levels in patients, indicating strong activation of inflammatory and antiviral immune pathways (p<0.01). ROC curve analysis demonstrated excellent diagnostic performance of defensins and cytokines to distinguish chronic HCV patients from controls, with area under the curve values ranging from 0.849 to 0.950 units. In conclusion, the circulation of defensins and inflammatory cytokines is markedly up-regulated in chronic HCV and has high diagnostic utility indicating their potential as immune biomarkers for chronic HCV-related inflammation and immune dysregulation.