Association between IFN-λ 3 Gene Polymorphisms and Outcome of Treatment with Direct Acting Antivirals in Chronic HCV-Infected Egyptian Patients

Immunol Invest. 2021 Jan;50(1):12-22. doi: 10.1080/08820139.2020.1722158. Epub 2020 Feb 5.

Abstract

Background: Single nucleotide polymorphisms (SNPs) of the interferon lambda 3 (IFN-λ 3) gene are associated with viral clearance and treatment response in chronic hepatitis C virus (HCV) infection. Aim: to assess whether specific IFN-λ 3 gene SNP, known as rs12979860 (C > T), could predict the outcome of treatment with direct acting antivirals (DAAs) among Egyptian patients with chronic HCV genotype 4 infection. Methods: Tetra-primer (ARMS-PCR) and PCR-RFLP methods were used for SNP genotyping in 100 chronic HCV-infected patients and 50 healthy subjects as control group. Results: The CC (wild type) genotype of rs12979860 was identified in 20 patients, 50% of them achieved sustained virological response (SVR). SNP genotype TT was found in 17 patients and only 2 of them (11.76%) were responders. The frequency of CT genotypes was significantly higher in responders than in non-responders (p= .021). In contrast, the frequency of TT genotypes was significantly higher in non-responders (42.85%, p< .001). On univariate and multivariate logistic regression analyses of the significant predictors of SVR, there were six predictive factors (Age, diabetes mellitus, AST, albumin, type of therapy and IFN-λ 3 genotype). Conclusion: The TT genotype and T allele were significantly associated with failure to achieve SVR. However, CT genotype of IFN-λ 3 (rs12979860) may be considered as a predictor for SVR in patients who received DAAs.

Keywords: HCV; SVR; direct acting antivirals; interferon lambda 3 (IFN-λ 3); single nucleotide polymorphisms.

MeSH terms

  • Alleles
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Egypt
  • Genotype
  • Hepacivirus*
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / virology
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / genetics
  • Humans
  • Interferons / genetics*
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Treatment Failure
  • Treatment Outcome

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • Interferons