Direct acting antiviral drugs reduce CXCL10 gene expression and reverse metabolic dysfunction in chronic HCV-infected patients

Abstract Background Hepatitis C virus (HCV) invades the host’s immune system and induces various metabolic changes. Therefore, we aimed to investigate the relative gene expression of the chemokine ligand CXCL10, along with some targeted metabolites, in chronic hepatitis C (CHC) patients receiving direct-acting antiviral drugs (DAAs), to identify potential biomarkers for viral eradication and therapeutic follow-up. Subjects and methods This prospective study included 50 patients with CHC who were evaluated before and 3 months after treatment with oral sofosbuvir/daclatasvir (SOF/DAC), as well as 50 healthy controls. All participants underwent history taking, full clinical examination, abdominal ultrasound and assessment of liver fibrosis. Laboratory investigations included liver function tests, alpha-fetoprotein (AFP), anti-HCV antibodies, HCV-RNA quantification and lipid profile. Relative expression levels of the CXCL10 gene were measured using real-time qPCR. Extended metabolic profiling of amino acids and acylcarnitines was performed using high Performance Liquid Chromatography Tandem Mass Spectrometry) HPLC–MS/MS). Results The relative quantity (RQ) of CXCL10 gene expression levels was significantly elevated in treatment-naïve CHC patients and showed a marked decline following therapy ( p < 0.001). Receiver operating characteristic (ROC) curve analysis revealed that CXCL10 RQ demonstrated excellent discrimination between pre-treatment CHC cases and controls (AUC = 0.980), with 98.0% sensitivity and 100% specificity. In post-treatment cases, CXCL10 RQ showed good discriminatory performance (AUC = 0.820), with 82% sensitivity and 80% specificity. Significant metabolic improvements were observed following DAA’s treatment. The amino acid profile demonstrated a significant decrease in the levels of nearly all amino acids while acylcarnitines increased across most short-, medium-, and long-chain species, with only C8 showing a significant decrease. Conclusion CXCL10 might play a role in hepatitis C pathogenesis, and its expression levels could serve as a marker of therapeutic response reflecting potent anti-inflammatory effects of DAAs. Differential metabolites may also provide non-invasive indicators of liver status and treatment prognosis.