Circular RNAs ‘circHIPK3’ and ‘circTCF25’ as Blood-Based Biomarkers for SVR and Relapse After Therapy in Chronic Hepatitis C Virus Infection

Abstract Introduction: Hepatitis C infection (HCV) is one of the most significant health concerns in developing nations, such as Pakistan. Different programs under the WHO HCV elimination oath are working on eliminating the virus by 2030. Circular RNAs (circRNAs) are potential novel therapeutic targets and diagnostic biomarkers for HCV infection. Methodology: There were 171 patients with HCV infection included in this study. The patients were graded in 2 groups: sustained virological response (SVR) and Relapse (Re) based on the response to the therapy. Expression levels for circHIPK3 and circTCF25 were analyzed with quantitative real-time PCR, and a ROC curve was created to test their potential as diagnostic tools. Competing endogenous networks were built, and GO analysis was carried out according to differentially and significantly expressed genes. Results The outcomes of our study revealed that the level of circHIPK3 was upregulated in the SVR and Relapse groups. The level of circHIPK3 in the SVR group was much higher than in the Relapse group (FC:19.83 vs. FC: 1.73). Also, circTCF25 was upregulated in SVR patients (FC:6.86) but downregulated in relapsed patients (FC: -1.47). ROC analysis revealed that the AUC value of circHIPK3 was 0.818 (p-value: 0.0084), and the value of circTCF25 was 0.867 (p-value: 0.0024). Bioinformatic analysis revealed that the Ras signaling pathway, Kaposi sarcoma-associated herpesvirus, and Hepatitis C virus are key involved pathways. Conclusion This study is important to discover the role of circRNAs in the 3a genotype of HCV in the Pakistani population. circHIPK3 and circTCF25 may serve as useful biomarkers to discriminate SVR from Relapse in HCV infection.