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Ibrahim MK, AbdElrahman M, Bader El Din NG, et al. The impact of genetic variations in sofosbuvir metabolizing enzymes and innate immunity mediators on treatment outcome in HCV-infected patients. Microb Pathog. 2021;162:105311doi: 10.1016/j.micpath.2021.105311.
Ibrahim, M. K., AbdElrahman, M., Bader El Din, N. G., Tawfik, S., Abd-Elsalam, S., Omran, D., Barakat, A. Z., Farouk, S., Elbatae, H., & El Awady, M. K. (2021). The impact of genetic variations in sofosbuvir metabolizing enzymes and innate immunity mediators on treatment outcome in HCV-infected patients. Microbial pathogenesis, 162105311. https://doi.org/10.1016/j.micpath.2021.105311
Ibrahim, Marwa K, et al. "The impact of genetic variations in sofosbuvir metabolizing enzymes and innate immunity mediators on treatment outcome in HCV-infected patients." Microbial pathogenesis vol. 162 (2021): 105311. doi: https://doi.org/10.1016/j.micpath.2021.105311
Ibrahim MK, AbdElrahman M, Bader El Din NG, Tawfik S, Abd-Elsalam S, Omran D, Barakat AZ, Farouk S, Elbatae H, El Awady MK. The impact of genetic variations in sofosbuvir metabolizing enzymes and innate immunity mediators on treatment outcome in HCV-infected patients. Microb Pathog. 2021 Nov 26;162:105311. doi: 10.1016/j.micpath.2021.105311. Epub 2021 Nov 26. PMID: 34843922.
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Microb Pathog. 2021 Nov 26;162:105311. doi: 10.1016/j.micpath.2021.105311. Epub 2021 Nov 26.

The impact of genetic variations in sofosbuvir metabolizing enzymes and innate immunity mediators on treatment outcome in HCV-infected patients.

Microbial pathogenesis

Marwa K Ibrahim, Mohamed AbdElrahman, Noha G Bader El Din, Salwa Tawfik, Sherief Abd-Elsalam, Dalia Omran, Amal Z Barakat, Sally Farouk, Hassan Elbatae, Mostafa K El Awady

Affiliations

  1. Department of Microbial Biotechnology, Biotechnology Research Institute, National Research Centre, 33 EL Bohouth St. (formerly El Tahrir St.), Dokki, Giza, P.O. 12622, Egypt. Electronic address: [email protected].
  2. Department of Pharmacy, Al-Mustaqbal University College, Babylon, Iraq; Clinical Pharmacy Unit, Badr University Hospital, Faculty of Medicine, Helwan University, Egypt.
  3. Department of Microbial Biotechnology, Biotechnology Research Institute, National Research Centre, 33 EL Bohouth St. (formerly El Tahrir St.), Dokki, Giza, P.O. 12622, Egypt.
  4. Department of Internal Medicine, National Research Center, 33 EL Bohouth St. (formerly El Tahrir St.), Dokki, Giza, P.O. 12622, Egypt.
  5. Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt.
  6. Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Egypt.
  7. Department of Molecular Biology, Biotechnology Research Institute, National Research Center, 33 EL Bohouth St. (formerly El Tahrir St.), Dokki, Giza, P.O. 12622, Egypt.
  8. Department of Tropical Medicine, Faculty of Medicine, Kafer Elshiek University, Kafer Elshiek, Egypt.

PMID: 34843922 DOI: 10.1016/j.micpath.2021.105311

Abstract

Hepatitis C virus (HCV) is the leading cause of liver diseases worldwide. At present, combinations of different classes of direct-acting antiviral agents (DAAs) are used as treatment options for HCV, in which sofosbuvir (SOF) is the common DAA among different therapeutic regimes. In Egypt, SOF plus daclatasvir (DCV) is the widely used anti-HCV treatment protocol. Herein, we aimed to assess the association between 3 single-nucleotide polymorphisms (SNPs) at the genes coding for 2 SOF metabolizing enzymes: histidine triad nucleotide-binding protein 1 (HINT1) rs4696/rs7728773 and nucleoside diphosphate kinase 1 (NME1) rs3760468, together with the most potent anti-HCV innate molecule, i.e., interferon lambda 3 (IFNL3) rs12979860 and the response to SOF/DCV in Egyptian patients chronically infected with genotype 4 (GT4). SNPs were genotyped using real-time PCR in DNA from patients who achieved sustained virological response (SVR) at 12 weeks post-SOF/DCV treatment (i.e., responders; n = 188), patients who failed to achieve SVR12 (i.e., non-responders; n = 109), and healthy controls (n = 62). Our results demonstrated that patients bearing HINT1 rs7728773 CT/TT (odds ratio 2.119, 95% CI 1.263-3.559, p = 0.005) and IFNL3 rs12979860 CC (odds ratio 3.995, 95% CI 2.126-7.740, p = 0.0001) were more likely to achieve SVR12. However, neither HINT1 rs4696 nor NME1 rs3760468 seems to contribute to the responsiveness to SOF/DCV. Binary regression analysis defined 5 predictor factors independently associated with SVR12: age, bilirubin, hemoglobin, early stages of fibrosis, and combined HINT1 rs7728773 and IFNL3 rs12979860 favorable and mixed genotypes (odds ratio 3.134, 95% CI 1.518-6.47, p = 0.002), and that was confirmed by the combined ROC curve for the 5 predictor factors (AUC = 0.91, 95% CI 0.869-0.95, P = 0.0001). In conclusion, these data suggest that the two SNPs have the potential in predicting the response rate to SOF/DCV treatment in patients infected with HCV GT4. This study is the first to investigate the pharmacogenetics of SOF metabolizing enzyme and introduce HINT1 rs7728773 as a novel SNP that predicts the treatment efficacy.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Keywords: Direct acting antivirals; Drug metabolism; Hepatitis C virus; Infectious disease; Single nucleotide polymorphism; Sustained virological response

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