IL-4, IL-17, and IL-22 genetic variants correlate with hepatitis C DAA treatment success in Pakistani patients

Hepatitis C virus (HCV) infection remains a significant global health burden, leading to chronic liver disease, cirrhosis, and hepatocellular carcinoma. Direct-acting antivirals (DAAs) have revolutionized HCV treatment, achieving high cure rates. However, treatment response can vary among individuals, with some patients experiencing relapse or non-response. Understanding the genetic factors that modulate the host immune response, particularly cytokine pathways like those involving interleukins, is crucial for predicting treatment outcomes and personalizing therapeutic strategies. This study addresses the gap in identifying specific genetic biomarkers that influence DAA efficacy in diverse populations.

Researchers conducted a cohort study on HCV-infected patients from various regions of Pakistan receiving direct-acting antiviral (DAA) therapy. The study aimed to correlate specific interleukin gene variants with treatment outcomes. Patients underwent detailed virological response analysis at specific intervals, with Sustained Virological Response (SVR12) defined as undetectable HCV RNA 12 weeks post-treatment completion. Genetic profiling involved sequencing analysis of three single-nucleotide polymorphisms (SNPs): 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). A small group of n = 4 healthy controls was included for comparative genetic analysis.

The genetic profiling revealed significant associations between specific interleukin variants and DAA treatment success. For IL-4 rs2243250, the heterozygous CT genotype was predominant in 52% of patients achieving SVR, compared to 37% in relapse patients. The IL-17 rs612242 SNP showed the AG genotype in 54% of SVR patients versus 39% in relapse cases. Similarly, the IL-22 rs2064501 SNP's AG genotype was prevalent in 49% of SVR patients, contrasting with 32% in relapse patients. A homozygous T/T genotype for IL-4 rs2243250 was observed in a relatively small percentage (16%) of non-responders. These findings underscore the role of host genetics in modulating antiviral response. The study confirmed the influence of these SNPs on DAA therapy success, highlighting specific genotypes associated with viral clearance. The comparison with healthy controls, though limited, supported the observed genetic variations. The overall findings indicate a strong correlation between specific genetic profiles and treatment efficacy. The study found that C/T, C/C, and A/G genotypes were dominant in patients who cleared the infection after treatment. This confirmed the influence of single-nucleotide polymorphisms on the success rate of DAAs therapy. The genetic factors of selected patients were compared with healthy controls.