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Interferon lambda 4 gene polymorphisms as a predicting tool of response to hepatitis C virus genotype 4 patients

Amany A Sakr1, Amr E Ahmed1, Mohamed D E Abd El-Maksoud2

  • 1Department of Biotechnology, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Egypt.

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases
|October 31, 2020
PubMed

Insights

Interferon lambda 4 (IFNL4) gene single nucleotide polymorphisms significantly predict treatment response in Hepatitis C Virus (HCV) genotype 4 patients receiving direct-acting antiviral (DAA) therapy. IFNL4 genotyping can guide personalized Sofosbuvir and Ribavirin treatment selection.

Area of Science:

  • Genetics
  • Hepatology
  • Pharmacogenomics

Background:

  • The relationship between interferon lambda 4 (IFNL4) gene polymorphisms and treatment outcomes with direct-acting antiviral (DAA) regimens in Hepatitis C Virus (HCV) infected patients remains unclear.
  • Understanding IFNL4 genotype associations can optimize DAA therapy selection for improved HCV clearance.
  • IFNL4, previously known as IL28B, plays a role in innate immune responses to viral infections.

Purpose of the Study:

  • To investigate the association between IFNL4 gene single nucleotide polymorphisms (SNPs) and treatment response in patients with chronic HCV genotype 4.
  • To determine if IFNL4 genotyping can aid in selecting appropriate DAA regimens, specifically Sofosbuvir (SOF) and Ribavirin (RBV), for personalized HCV treatment.
  • To evaluate the correlation of IFNL4 genotypes with sustained virological response in HCV genotype 4 patients.

Main Methods:

  • Genomic DNA was extracted from whole blood samples of 100 patients with chronic HCV genotype 4 and 50 healthy controls.
  • SNP genotyping assay for the IFNL4 gene (rs368234815) was performed.
  • Patients were classified into responders and non-responders based on their response to SOF and RBV treatment.

Main Results:

  • A significant association was found between IFNL4 genotypes and treatment response to SOF/RBV (p < 0.001).
  • The TT/TT homozygous genotype was more prevalent in responders (60%) compared to non-responders.
  • No significant correlation was observed between gender, age, ALT, or PLC and treatment response, while INR showed some association.

Conclusions:

  • IFNL4 gene polymorphisms are significant predictors of treatment response in HCV genotype 4 patients treated with Sofosbuvir and Ribavirin.
  • IFNL4 genotyping holds potential for guiding personalized DAA therapy selection in HCV management.
  • Further research is warranted to elucidate the precise mechanisms underlying IFNL4's influence on DAA efficacy.
Keywords:
Genotype 4HCVIFNL4 polymorphismsRibavirinSofosbuvir

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