1887

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Volume 97, Issue 10

Can polymorphisms predict response to interferon/ribavirin treatment in hepatitis C patients with genotype 3? Free

Abstract

Favourable genotypes of polymorphism CC for rs12979860 and TT for rs8099917 are strongly associated with the interferon/ribavirin treatment outcome in hepatitis C virus (HCV) patients with genotypes 1 and 4. Contrarily, conflicting results have been reported for patients with HCV genotypes 2 and 3. Therefore, we sought to investigate the association between with sustained virological response (SVR) after treatment to ascertain the predictive value of single-nucleotide polymorphisms (SNPs) in HCV patients with genotype 3. For this purpose, we genotyped five SNPs, rs12980275, rs12979860, rs9109886, rs8099917 and rs7248668, in HCV patients with genotype 3 and assessed its association with SVR, individually and in haplotype. Interestingly, we report that the SNPs we genotyped have shown no association with SVR following treatment, either individually or in haplotype, indicating that genotyping SNPs have limited predictive value in HCV patients with genotype 3. Therefore, we propose that genotyping can be excluded from a patient’s pre-treatment workup for subsequent treatment choice. This will greatly reduce the economic burden for HCV patients with genotype 3 in resource-limited regions, especially South Asia where genotype 3 is predominant.

  • Received:
  • Accepted:
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Keyword(s): genotype 3 , Hepatitis C virus , IFNL3 , interferon/ribavirin treatment , rs12979860 and rs8099917
© 2016 The Authors
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2016-10-13
2024-04-27
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References

  1. Anon. 2011; EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol 55:245–264 [View Article][PubMed]
     [Google Scholar]
  2. Anon. 2015; EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol 63:199–236 [View Article][PubMed]
     [Google Scholar]
  3. Asselah T., De Muynck S., Broët P., Masliah-Planchon J., Blanluet M., Bièche I., Lapalus M., Martinot-Peignoux M., Lada O. et al. 2012; IL28B polymorphism is associated with treatment response in patients with genotype 4 chronic hepatitis C. J Hepatol 56:527–532 [View Article][PubMed]
     [Google Scholar]
  4. Bibert S., Roger T., Calandra T., Bochud M., Cerny A., Semmo N., Duong F. H., Gerlach T., Malinverni R. et al. 2013; IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction. J Exp Med 210:1109–1116 [View Article][PubMed]
     [Google Scholar]
  5. Ge D., Fellay J., Thompson A. J., Simon J. S., Shianna K. V., Urban T. J., Heinzen E. L., Qiu P., Bertelsen A. H. et al. 2009; Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461:399–401 [View Article][PubMed]
     [Google Scholar]
  6. Ghany M. G., Nelson D. R., Strader D. B., Thomas D. L., Seeff L. B. 2011; An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology 54:1433–1444 [View Article][PubMed]
     [Google Scholar]
  7. Hashmi A. H., Ahmad N., Riaz S., Ali L., Siddiqi S., Khan K. M., Shakoori A. R., Mansoor A. 2014; Genotype CC of rs12979860 is providing protection against infection rather than assisting in treatment response for HCV genotype 3a infection. Genes Immun 15:430–432 [View Article][PubMed]
     [Google Scholar]
  8. Jia Z., Ding Y., Tian S., Niu J., Jiang J. 2012; Test of IL28B polymorphisms in chronic hepatitis C patients treated with PegIFN and ribavirin depends on HCV genotypes: results from a meta-analysis. PLoS One 7:e45698 [View Article][PubMed]
     [Google Scholar]
  9. Jiménez-Sousa M. A., Fernández-Rodríguez A., Guzmán-Fulgencio M., García-Álvarez M., Resino S. 2013; Meta-analysis: implications of interleukin-28B polymorphisms in spontaneous and treatment-related clearance for patients with hepatitis C. BMC Medicine 11:6 [View Article]
     [Google Scholar]
  10. Kotenko S. V., Gallagher G., Baurin V. V., Lewis-Antes A., Shen M., Shah N. K., Langer J. A., Sheikh F., Dickensheets H. et al. 2003; IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 4:69–77 [View Article][PubMed]
     [Google Scholar]
  11. Lin C. Y., Chen J. Y., Lin T. N., Jeng W. J., Huang C. H., Huang C. W., Chang S. W., Sheen I. S. 2011; IL28B SNP rs12979860 is a critical predictor for on-treatment and sustained virologic response in patients with hepatitis C virus genotype-1 infection. PLoS One 6:e18322 [View Article][PubMed]
     [Google Scholar]
  12. Lu Y.-F., Mauger D. M., Goldstein D. B., Urban T. J., Weeks K. M., Bradrick S. S. 2015; IFNL3 mRNA structure is remodeled by a functional non-coding polymorphism associated with hepatitis C virus clearance. Sci Rep 5:16037 [View Article][PubMed]
     [Google Scholar]
  13. Mangia A., Thompson A. J., Santoro R., Piazzolla V., Tillmann H. L., Patel K., Shianna K. V., Mottola L., Petruzzellis D. et al. 2010; An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response. Gastroenterology 139:821–827 [View Article][PubMed]
     [Google Scholar]
  14. Marcello T., Grakoui A., Barba-Spaeth G., Machlin E. S., Kotenko S. V., MacDonald M. R., Rice C. M. 2006; Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Gastroenterology 131:1887–1898 [View Article][PubMed]
     [Google Scholar]
  15. McFarland A. P., Horner S. M., Jarret A., Joslyn R. C., Bindewald E., Shapiro B. A., Delker D. A., Hagedorn C. H., Carrington M. et al. 2014; The favorable IFNL3 genotype escapes mRNA decay mediated by AU-rich elements and hepatitis C virus-induced microRNAs. Nat Immunol 15:72–79 [View Article][PubMed]
     [Google Scholar]
  16. Messina J. P., Humphreys I., Flaxman A., Brown A., Cooke G. S., Pybus O. G., Barnes E. 2015; Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 61:77–87 [View Article][PubMed]
     [Google Scholar]
  17. Moghaddam A., Melum E., Reinton N., Ring-Larsen H., Verbaan H., Bjøro K., Dalgard O. 2011; IL28B genetic variation and treatment response in patients with hepatitis C virus genotype 3 infection. Hepatology 53:746–754 [View Article][PubMed]
     [Google Scholar]
  18. O'Brien T. R., Pfeiffer R. M., Paquin A., Lang Kuhs K. A., Chen S., Bonkovsky H. L., Edlin B. R., Howell C. D., Kirk G. D. et al. 2015; Comparison of functional variants in IFNL4 and IFNL3 for association with HCV clearance. J Hepatol 63:1103–1110 [View Article][PubMed]
     [Google Scholar]
  19. Ohno O., Mizokami M., Wu R. R., Saleh M. G., Ohba K., Orito E., Mukaide M., Williams R., Lau J. Y. 1997; New hepatitis C virus (HCV) genotyping system that allows for identification of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a. J Clin Microbiol 35:201–207[PubMed]
     [Google Scholar]
  20. Prokunina-Olsson L., Muchmore B., Tang W., Pfeiffer R. M., Park H., Dickensheets H., Hergott D., Porter-Gill P., Mumy A. et al. 2013; A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet 45:164–171 [View Article][PubMed]
     [Google Scholar]
  21. Rauch A., Kutalik Z., Descombes P., Cai T., Di Iulio J., Mueller T., Bochud M., Battegay M., Bernasconi E. et al. 2010; Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology 138:1338–1345 [View Article][PubMed]
     [Google Scholar]
  22. Rozen S., Skaletsky H. 2000; Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132:365–386[PubMed]
     [Google Scholar]
  23. Sarrazin C., Susser S., Doehring A., Lange C. M., Müller T., Schlecker C., Herrmann E., Lötsch J., Berg T. 2011; Importance of IL28B gene polymorphisms in hepatitis C virus genotype 2 and 3 infected patients. J Hepatol 54:415–421 [View Article][PubMed]
     [Google Scholar]
  24. Sharafi H., Alavian S. M. 2011; IL28B polymorphism, explanation for different responses to therapy in hepatitis C patients. Hepat Mon 11:958–959 [View Article][PubMed]
     [Google Scholar]
  25. Sheppard P., Kindsvogel W., Xu W., Henderson K., Schlutsmeyer S., Whitmore T. E., Kuestner R., Garrigues U., Birks C. et al. 2003; IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol 4:63–68 [View Article][PubMed]
     [Google Scholar]
  26. Sherry S. T., Ward M. H., Kholodov M., Baker J., Phan L., Smigielski E. M., Sirotkin K. 2001; dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29:308–311 [View Article][PubMed]
     [Google Scholar]
  27. Shirakawa H., Matsumoto A., Joshita S., Komatsu M., Tanaka N., Umemura T., Ichijo T., Yoshizawa K., Kiyosawa K. et al. 2008; Pretreatment prediction of virological response to peginterferon plus ribavirin therapy in chronic hepatitis C patients using viral and host factors. Hepatology 48:1753–1760 [View Article][PubMed]
     [Google Scholar]
  28. Stephens M., Scheet P. 2005; Accounting for decay of linkage disequilibrium in haplotype inference and missing-data imputation. Am J Hum Genet 76:449–462 [View Article][PubMed]
     [Google Scholar]
  29. Stephens M., Smith N. J., Donnelly P. 2001; A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68:978–989 [View Article][PubMed]
     [Google Scholar]
  30. Suppiah V., Moldovan M., Ahlenstiel G., Berg T., Weltman M., Abate M. L., Bassendine M., Spengler U., Dore G. J. et al. 2009; IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 41:1100–1104 [View Article][PubMed]
     [Google Scholar]
  31. Tanaka Y., Nishida N., Sugiyama M., Kurosaki M., Matsuura K., Sakamoto N., Nakagawa M., Korenaga M., Hino K. et al. 2009; Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 41:1105–1109 [View Article][PubMed]
     [Google Scholar]
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Can IFNL3 polymorphisms predict response to interferon/ribavirin treatment in hepatitis C patients with genotype 3?
J. Gen. Virol. 97, 2592 (2016); https://doi.org/10.1099/jgv.0.000572
/content/journal/jgv/10.1099/jgv.0.000572
/content/journal/jgv/10.1099/jgv.0.000572
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