Genetic Profiling of Interleukin Variants and their Correlation with Hepatitis C Viral Response to Different Therapeutic Strategies Administered in Pakistani Patients

This research study aimed to investigate the response of patients infected with the hepatitis C virus (HCV) toward direct-acting antivirals (DAAs) therapy. The research included a cohort of HCV-infected patients from different regions of Pakistan. Experimental studies were performed for the detailed analysis of virological response recorded at specific time intervals during the whole course of treatment. Sustained virological response (SVR) was explicitly defined as undetectable HCV RNA at 12 weeks post-completion of therapy (SVR12), ensuring alignment with international clinical standards. The standard genotypes analyzed for the selected interleukin (IL) variants were: IL-4 rs2243250 (C/C, C/T, T/T), IL-17 rs612242 (A/A, A/G, G/G), and IL-22 rs2064501 (A/A, A/G, G/G). The genetic profiling of these variants highlighted the significant role of cytokines in modulating the patient's immune response. The research also focused on the association between single-nucleotide polymorphisms (SNPs) of IL genes and categorization based on the outcomes of treatment by sequencing analysis. Our study found that the IL-4 rs2243250 SNP was predominantly heterozygous as CT in 52% SVR and 37% relapse patients. The IL-17 rs612242 SNP was mainly identified as AG in 54% SVR and 39% relapse patients, and the IL-22 rs2064501 SNP was prevalent in 32% relapse and 49% SVR patients as AG genotype. A homozygous genotype T/T was also analyzed for polymorphism rs2243250 in a relatively small percentage (16%) of non-responders. These research findings showed that C/T, C/C, and A/G genotypes were dominant in patients who cleared the infection after treatment. It confirmed the influence of single-nucleotide polymorphisms on the success rate of DAAs therapy, determined by observing the baseline characteristics and genetic factors of selected patients after comparing with healthy controls. Due to the limited genotyping of healthy controls ( n = 4), comparative results involving the control group were interpreted with caution.