IFNL3 polymorphisms predict response to therapy in chronic hepatitis C genotype 2/3 infection

Mohammed Eslam, Reynold Leung, Manuel Romero-Gomez, Alessandra Mangia, William L. Irving, David Sheridan, Ulrich Spengler, Lindsay Mollison, Wendy Cheng, Elisabetta Bugianesi, Duncan McLeod, Abed M. Zaitoun, Vito Attino, Diane Goeltz, Jacob Nattermann, Mark Douglas, David R. Booth, Jacob George, Golo Ahlenstiel

Research output: Contribution to journalArticle

Abstract

Background & Aims Single nucleotide polymorphisms (SNPs) near the interferon lambda 3 (IFNL3, previously known as IL28B) region are the strongest baseline predictors of sustained virologic response (SVR) to pegylated interferon and ribavirin therapy in hepatitis C virus (HCV) genotype 1 infection. Whether IFNL3 SNPs influence treatment response in genotype 2 and 3 (HCV-2/3) infection remains controversial. This study sought to clarify in a large cohort, whether SNPs in the IFNL3 region are associated with treatment response in HCV-2/3 patients. Methods The cohort comprised 1002 HCV-2/3 Caucasians patients treated with pegylated interferon-alpha and ribavirin who underwent genotyping for the SNPs rs12979860 and rs8099917. Results Overall, 736 (73.5%) patients achieved SVR (81.9%, 67.9%, and 57.8% for rs12979860 CC, CT, and TT [p = 0.0001]; 78%, 68.7%, and 46.3% for rs8099917 TT, TG, and GG [p = 0.0001]). By logistic regression, both rs12979860 CC and rs8099917 TT were independent predictors of SVR with an odds ratio (OR) of 2.39 (1.19-3.81) p = 0.0001 and OR 1.85 (1.15-2.23) p = 0.0001, respectively. IFNL3 responder genotypes were more frequent in relapsers than null-responders (p = 0.0001 for both SNPs). On-treatment rapid virological response (RVR) was predictive of SVR only in those individuals with IFNL3 non-responder genotypes (rs12979860 CT/TT and rs8099917 TG/GG). Conclusions This adequately powered study in patients with HCV genotypes 2 or 3 infection clearly demonstrates that IFNL3 genotypes are the strongest baseline predictor of SVR, in keeping with the known association for genotype 1 infection. IFNL3 genotyping can aid in therapeutic decision making for these patients.

Original languageEnglish
Pages (from-to)235-241
Number of pages7
JournalJournal of Hepatology
Volume61
Issue number2
DOIs
Publication statusPublished - 2014

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Chronic Hepatitis C
Genotype
Hepacivirus
Single Nucleotide Polymorphism
Infection
Ribavirin
Interferons
Therapeutics
Odds Ratio
Interferon-alpha
Decision Making
Logistic Models
Sustained Virologic Response

Keywords

  • Chronic hepatitis C
  • Genotype 2
  • Genotype 3
  • IFNL3 (IL28B)
  • Response to therapy
  • SVR

ASJC Scopus subject areas

  • Hepatology

Cite this

Eslam, M., Leung, R., Romero-Gomez, M., Mangia, A., Irving, W. L., Sheridan, D., ... Ahlenstiel, G. (2014). IFNL3 polymorphisms predict response to therapy in chronic hepatitis C genotype 2/3 infection. Journal of Hepatology, 61(2), 235-241. https://doi.org/10.1016/j.jhep.2014.03.039

IFNL3 polymorphisms predict response to therapy in chronic hepatitis C genotype 2/3 infection. / Eslam, Mohammed; Leung, Reynold; Romero-Gomez, Manuel; Mangia, Alessandra; Irving, William L.; Sheridan, David; Spengler, Ulrich; Mollison, Lindsay; Cheng, Wendy; Bugianesi, Elisabetta; McLeod, Duncan; Zaitoun, Abed M.; Attino, Vito; Goeltz, Diane; Nattermann, Jacob; Douglas, Mark; Booth, David R.; George, Jacob; Ahlenstiel, Golo.

In: Journal of Hepatology, Vol. 61, No. 2, 2014, p. 235-241.

Research output: Contribution to journalArticle

Eslam, M, Leung, R, Romero-Gomez, M, Mangia, A, Irving, WL, Sheridan, D, Spengler, U, Mollison, L, Cheng, W, Bugianesi, E, McLeod, D, Zaitoun, AM, Attino, V, Goeltz, D, Nattermann, J, Douglas, M, Booth, DR, George, J & Ahlenstiel, G 2014, 'IFNL3 polymorphisms predict response to therapy in chronic hepatitis C genotype 2/3 infection', Journal of Hepatology, vol. 61, no. 2, pp. 235-241. https://doi.org/10.1016/j.jhep.2014.03.039
Eslam, Mohammed ; Leung, Reynold ; Romero-Gomez, Manuel ; Mangia, Alessandra ; Irving, William L. ; Sheridan, David ; Spengler, Ulrich ; Mollison, Lindsay ; Cheng, Wendy ; Bugianesi, Elisabetta ; McLeod, Duncan ; Zaitoun, Abed M. ; Attino, Vito ; Goeltz, Diane ; Nattermann, Jacob ; Douglas, Mark ; Booth, David R. ; George, Jacob ; Ahlenstiel, Golo. / IFNL3 polymorphisms predict response to therapy in chronic hepatitis C genotype 2/3 infection. In: Journal of Hepatology. 2014 ; Vol. 61, No. 2. pp. 235-241.
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abstract = "Background & Aims Single nucleotide polymorphisms (SNPs) near the interferon lambda 3 (IFNL3, previously known as IL28B) region are the strongest baseline predictors of sustained virologic response (SVR) to pegylated interferon and ribavirin therapy in hepatitis C virus (HCV) genotype 1 infection. Whether IFNL3 SNPs influence treatment response in genotype 2 and 3 (HCV-2/3) infection remains controversial. This study sought to clarify in a large cohort, whether SNPs in the IFNL3 region are associated with treatment response in HCV-2/3 patients. Methods The cohort comprised 1002 HCV-2/3 Caucasians patients treated with pegylated interferon-alpha and ribavirin who underwent genotyping for the SNPs rs12979860 and rs8099917. Results Overall, 736 (73.5{\%}) patients achieved SVR (81.9{\%}, 67.9{\%}, and 57.8{\%} for rs12979860 CC, CT, and TT [p = 0.0001]; 78{\%}, 68.7{\%}, and 46.3{\%} for rs8099917 TT, TG, and GG [p = 0.0001]). By logistic regression, both rs12979860 CC and rs8099917 TT were independent predictors of SVR with an odds ratio (OR) of 2.39 (1.19-3.81) p = 0.0001 and OR 1.85 (1.15-2.23) p = 0.0001, respectively. IFNL3 responder genotypes were more frequent in relapsers than null-responders (p = 0.0001 for both SNPs). On-treatment rapid virological response (RVR) was predictive of SVR only in those individuals with IFNL3 non-responder genotypes (rs12979860 CT/TT and rs8099917 TG/GG). Conclusions This adequately powered study in patients with HCV genotypes 2 or 3 infection clearly demonstrates that IFNL3 genotypes are the strongest baseline predictor of SVR, in keeping with the known association for genotype 1 infection. IFNL3 genotyping can aid in therapeutic decision making for these patients.",
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AU - Eslam, Mohammed

AU - Leung, Reynold

AU - Romero-Gomez, Manuel

AU - Mangia, Alessandra

AU - Irving, William L.

AU - Sheridan, David

AU - Spengler, Ulrich

AU - Mollison, Lindsay

AU - Cheng, Wendy

AU - Bugianesi, Elisabetta

AU - McLeod, Duncan

AU - Zaitoun, Abed M.

AU - Attino, Vito

AU - Goeltz, Diane

AU - Nattermann, Jacob

AU - Douglas, Mark

AU - Booth, David R.

AU - George, Jacob

AU - Ahlenstiel, Golo

PY - 2014

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N2 - Background & Aims Single nucleotide polymorphisms (SNPs) near the interferon lambda 3 (IFNL3, previously known as IL28B) region are the strongest baseline predictors of sustained virologic response (SVR) to pegylated interferon and ribavirin therapy in hepatitis C virus (HCV) genotype 1 infection. Whether IFNL3 SNPs influence treatment response in genotype 2 and 3 (HCV-2/3) infection remains controversial. This study sought to clarify in a large cohort, whether SNPs in the IFNL3 region are associated with treatment response in HCV-2/3 patients. Methods The cohort comprised 1002 HCV-2/3 Caucasians patients treated with pegylated interferon-alpha and ribavirin who underwent genotyping for the SNPs rs12979860 and rs8099917. Results Overall, 736 (73.5%) patients achieved SVR (81.9%, 67.9%, and 57.8% for rs12979860 CC, CT, and TT [p = 0.0001]; 78%, 68.7%, and 46.3% for rs8099917 TT, TG, and GG [p = 0.0001]). By logistic regression, both rs12979860 CC and rs8099917 TT were independent predictors of SVR with an odds ratio (OR) of 2.39 (1.19-3.81) p = 0.0001 and OR 1.85 (1.15-2.23) p = 0.0001, respectively. IFNL3 responder genotypes were more frequent in relapsers than null-responders (p = 0.0001 for both SNPs). On-treatment rapid virological response (RVR) was predictive of SVR only in those individuals with IFNL3 non-responder genotypes (rs12979860 CT/TT and rs8099917 TG/GG). Conclusions This adequately powered study in patients with HCV genotypes 2 or 3 infection clearly demonstrates that IFNL3 genotypes are the strongest baseline predictor of SVR, in keeping with the known association for genotype 1 infection. IFNL3 genotyping can aid in therapeutic decision making for these patients.

AB - Background & Aims Single nucleotide polymorphisms (SNPs) near the interferon lambda 3 (IFNL3, previously known as IL28B) region are the strongest baseline predictors of sustained virologic response (SVR) to pegylated interferon and ribavirin therapy in hepatitis C virus (HCV) genotype 1 infection. Whether IFNL3 SNPs influence treatment response in genotype 2 and 3 (HCV-2/3) infection remains controversial. This study sought to clarify in a large cohort, whether SNPs in the IFNL3 region are associated with treatment response in HCV-2/3 patients. Methods The cohort comprised 1002 HCV-2/3 Caucasians patients treated with pegylated interferon-alpha and ribavirin who underwent genotyping for the SNPs rs12979860 and rs8099917. Results Overall, 736 (73.5%) patients achieved SVR (81.9%, 67.9%, and 57.8% for rs12979860 CC, CT, and TT [p = 0.0001]; 78%, 68.7%, and 46.3% for rs8099917 TT, TG, and GG [p = 0.0001]). By logistic regression, both rs12979860 CC and rs8099917 TT were independent predictors of SVR with an odds ratio (OR) of 2.39 (1.19-3.81) p = 0.0001 and OR 1.85 (1.15-2.23) p = 0.0001, respectively. IFNL3 responder genotypes were more frequent in relapsers than null-responders (p = 0.0001 for both SNPs). On-treatment rapid virological response (RVR) was predictive of SVR only in those individuals with IFNL3 non-responder genotypes (rs12979860 CT/TT and rs8099917 TG/GG). Conclusions This adequately powered study in patients with HCV genotypes 2 or 3 infection clearly demonstrates that IFNL3 genotypes are the strongest baseline predictor of SVR, in keeping with the known association for genotype 1 infection. IFNL3 genotyping can aid in therapeutic decision making for these patients.

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KW - Response to therapy

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