Interleukin-28B Polymorphism Improves Viral Kinetics and Is the Strongest Pretreatment Predictor of Sustained Virologic Response in Genotype 1 Hepatitis C Virus

Alexander J. Thompson, Andrew J. Muir, Mark S. Sulkowski, Dongliang Ge, Jacques Fellay, Kevin V. Shianna, Thomas Urban, Nezam H. Afdhal, Ira M. Jacobson, Rafael Esteban, Fred Poordad, Eric J. Lawitz, Jonathan McCone, Mitchell L. Shiffman, Greg W. Galler, William M. Lee, Robert Reindollar, John W. King, Paul Y. Kwo, Reem H. GhalibBradley Freilich, Lisa M. Nyberg, Stefan Zeuzem, Thierry Poynard, David M. Vock, Karen S. Pieper, Keyur Patel, Hans L. Tillmann, Stephanie Noviello, Kenneth Koury, Lisa D. Pedicone, Clifford A. Brass, Janice K. Albrecht, David B. Goldstein, John G. McHutchison

Research output: Contribution to journalArticle

619 Citations (Scopus)

Abstract

Background & Aims: We recently identified a polymorphism upstream of interleukin (IL)-28B to be associated with a 2-fold difference in sustained virologic response (SVR) rates to pegylated interferon-alfa and ribavirin therapy in a large cohort of treatment-naive, adherent patients with chronic hepatitis C virus genotype 1 (HCV-1) infection. We sought to confirm the polymorphism's clinical relevance by intention-to-treat analysis evaluating on-treatment virologic response and SVR. Methods: HCV-1 patients were genotyped as CC, CT, or TT at the polymorphic site, rs12979860. Viral kinetics and rates of rapid virologic response (RVR, week 4), complete early virologic response (week 12), and SVR were compared by IL-28B type in 3 self-reported ethnic groups: Caucasians (n = 1171), African Americans (n = 300), and Hispanics (n = 116). Results: In Caucasians, the CC IL-28B type was associated with improved early viral kinetics and greater likelihood of RVR (28% vs 5% and 5%; P < .0001), complete early virologic response (87% vs 38% and 28%; P < .0001), and SVR (69% vs 33% and 27%; P < .0001) compared with CT and TT. A similar association occurred within African Americans and Hispanics. In a multivariable regression model, CC IL-28B type was the strongest pretreatment predictor of SVR (odds ratio, 5.2; 95% confidence interval, 4.1-6.7). RVR was a strong predictor of SVR regardless of IL-28B type. In non-RVR patients, the CC IL-28B type was associated with a higher rate of SVR (Caucasians, 66% vs 31% and 24%; P < .0001). Conclusions: In treatment-naive HCV-1 patients treated with pegylated interferon and ribavirin, a polymorphism upstream of IL-28B is associated with increased on-treatment and sustained virologic response and effectively predicts treatment outcome.

Original languageEnglish
JournalGastroenterology
Volume139
Issue number1
DOIs
StatePublished - Jul 2010

Fingerprint

Interleukins
Hepacivirus
Genotype
Ribavirin
Hispanic Americans
African Americans
Therapeutics
Intention to Treat Analysis
Sustained Virologic Response
Chronic Hepatitis C
Ethnic Groups
Interferon-alpha
Interferons
Odds Ratio
Confidence Intervals
Infection

Keywords

  • Genetics
  • IL-28B
  • Interferon-Lambda
  • Peg-Interferon-Alfa

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Interleukin-28B Polymorphism Improves Viral Kinetics and Is the Strongest Pretreatment Predictor of Sustained Virologic Response in Genotype 1 Hepatitis C Virus. / Thompson, Alexander J.; Muir, Andrew J.; Sulkowski, Mark S.; Ge, Dongliang; Fellay, Jacques; Shianna, Kevin V.; Urban, Thomas; Afdhal, Nezam H.; Jacobson, Ira M.; Esteban, Rafael; Poordad, Fred; Lawitz, Eric J.; McCone, Jonathan; Shiffman, Mitchell L.; Galler, Greg W.; Lee, William M.; Reindollar, Robert; King, John W.; Kwo, Paul Y.; Ghalib, Reem H.; Freilich, Bradley; Nyberg, Lisa M.; Zeuzem, Stefan; Poynard, Thierry; Vock, David M.; Pieper, Karen S.; Patel, Keyur; Tillmann, Hans L.; Noviello, Stephanie; Koury, Kenneth; Pedicone, Lisa D.; Brass, Clifford A.; Albrecht, Janice K.; Goldstein, David B.; McHutchison, John G.

In: Gastroenterology, Vol. 139, No. 1, 07.2010.

Research output: Contribution to journalArticle

Thompson, AJ, Muir, AJ, Sulkowski, MS, Ge, D, Fellay, J, Shianna, KV, Urban, T, Afdhal, NH, Jacobson, IM, Esteban, R, Poordad, F, Lawitz, EJ, McCone, J, Shiffman, ML, Galler, GW, Lee, WM, Reindollar, R, King, JW, Kwo, PY, Ghalib, RH, Freilich, B, Nyberg, LM, Zeuzem, S, Poynard, T, Vock, DM, Pieper, KS, Patel, K, Tillmann, HL, Noviello, S, Koury, K, Pedicone, LD, Brass, CA, Albrecht, JK, Goldstein, DB & McHutchison, JG 2010, 'Interleukin-28B Polymorphism Improves Viral Kinetics and Is the Strongest Pretreatment Predictor of Sustained Virologic Response in Genotype 1 Hepatitis C Virus', Gastroenterology, vol. 139, no. 1. https://doi.org/10.1053/j.gastro.2010.04.013
Thompson, Alexander J. ; Muir, Andrew J. ; Sulkowski, Mark S. ; Ge, Dongliang ; Fellay, Jacques ; Shianna, Kevin V. ; Urban, Thomas ; Afdhal, Nezam H. ; Jacobson, Ira M. ; Esteban, Rafael ; Poordad, Fred ; Lawitz, Eric J. ; McCone, Jonathan ; Shiffman, Mitchell L. ; Galler, Greg W. ; Lee, William M. ; Reindollar, Robert ; King, John W. ; Kwo, Paul Y. ; Ghalib, Reem H. ; Freilich, Bradley ; Nyberg, Lisa M. ; Zeuzem, Stefan ; Poynard, Thierry ; Vock, David M. ; Pieper, Karen S. ; Patel, Keyur ; Tillmann, Hans L. ; Noviello, Stephanie ; Koury, Kenneth ; Pedicone, Lisa D. ; Brass, Clifford A. ; Albrecht, Janice K. ; Goldstein, David B. ; McHutchison, John G. / Interleukin-28B Polymorphism Improves Viral Kinetics and Is the Strongest Pretreatment Predictor of Sustained Virologic Response in Genotype 1 Hepatitis C Virus. In: Gastroenterology. 2010 ; Vol. 139, No. 1.
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abstract = "Background & Aims: We recently identified a polymorphism upstream of interleukin (IL)-28B to be associated with a 2-fold difference in sustained virologic response (SVR) rates to pegylated interferon-alfa and ribavirin therapy in a large cohort of treatment-naive, adherent patients with chronic hepatitis C virus genotype 1 (HCV-1) infection. We sought to confirm the polymorphism's clinical relevance by intention-to-treat analysis evaluating on-treatment virologic response and SVR. Methods: HCV-1 patients were genotyped as CC, CT, or TT at the polymorphic site, rs12979860. Viral kinetics and rates of rapid virologic response (RVR, week 4), complete early virologic response (week 12), and SVR were compared by IL-28B type in 3 self-reported ethnic groups: Caucasians (n = 1171), African Americans (n = 300), and Hispanics (n = 116). Results: In Caucasians, the CC IL-28B type was associated with improved early viral kinetics and greater likelihood of RVR (28{\%} vs 5{\%} and 5{\%}; P < .0001), complete early virologic response (87{\%} vs 38{\%} and 28{\%}; P < .0001), and SVR (69{\%} vs 33{\%} and 27{\%}; P < .0001) compared with CT and TT. A similar association occurred within African Americans and Hispanics. In a multivariable regression model, CC IL-28B type was the strongest pretreatment predictor of SVR (odds ratio, 5.2; 95{\%} confidence interval, 4.1-6.7). RVR was a strong predictor of SVR regardless of IL-28B type. In non-RVR patients, the CC IL-28B type was associated with a higher rate of SVR (Caucasians, 66{\%} vs 31{\%} and 24{\%}; P < .0001). Conclusions: In treatment-naive HCV-1 patients treated with pegylated interferon and ribavirin, a polymorphism upstream of IL-28B is associated with increased on-treatment and sustained virologic response and effectively predicts treatment outcome.",
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author = "Thompson, {Alexander J.} and Muir, {Andrew J.} and Sulkowski, {Mark S.} and Dongliang Ge and Jacques Fellay and Shianna, {Kevin V.} and Thomas Urban and Afdhal, {Nezam H.} and Jacobson, {Ira M.} and Rafael Esteban and Fred Poordad and Lawitz, {Eric J.} and Jonathan McCone and Shiffman, {Mitchell L.} and Galler, {Greg W.} and Lee, {William M.} and Robert Reindollar and King, {John W.} and Kwo, {Paul Y.} and Ghalib, {Reem H.} and Bradley Freilich and Nyberg, {Lisa M.} and Stefan Zeuzem and Thierry Poynard and Vock, {David M.} and Pieper, {Karen S.} and Keyur Patel and Tillmann, {Hans L.} and Stephanie Noviello and Kenneth Koury and Pedicone, {Lisa D.} and Brass, {Clifford A.} and Albrecht, {Janice K.} and Goldstein, {David B.} and McHutchison, {John G.}",
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TY - JOUR

T1 - Interleukin-28B Polymorphism Improves Viral Kinetics and Is the Strongest Pretreatment Predictor of Sustained Virologic Response in Genotype 1 Hepatitis C Virus

AU - Thompson, Alexander J.

AU - Muir, Andrew J.

AU - Sulkowski, Mark S.

AU - Ge, Dongliang

AU - Fellay, Jacques

AU - Shianna, Kevin V.

AU - Urban, Thomas

AU - Afdhal, Nezam H.

AU - Jacobson, Ira M.

AU - Esteban, Rafael

AU - Poordad, Fred

AU - Lawitz, Eric J.

AU - McCone, Jonathan

AU - Shiffman, Mitchell L.

AU - Galler, Greg W.

AU - Lee, William M.

AU - Reindollar, Robert

AU - King, John W.

AU - Kwo, Paul Y.

AU - Ghalib, Reem H.

AU - Freilich, Bradley

AU - Nyberg, Lisa M.

AU - Zeuzem, Stefan

AU - Poynard, Thierry

AU - Vock, David M.

AU - Pieper, Karen S.

AU - Patel, Keyur

AU - Tillmann, Hans L.

AU - Noviello, Stephanie

AU - Koury, Kenneth

AU - Pedicone, Lisa D.

AU - Brass, Clifford A.

AU - Albrecht, Janice K.

AU - Goldstein, David B.

AU - McHutchison, John G.

PY - 2010/7

Y1 - 2010/7

N2 - Background & Aims: We recently identified a polymorphism upstream of interleukin (IL)-28B to be associated with a 2-fold difference in sustained virologic response (SVR) rates to pegylated interferon-alfa and ribavirin therapy in a large cohort of treatment-naive, adherent patients with chronic hepatitis C virus genotype 1 (HCV-1) infection. We sought to confirm the polymorphism's clinical relevance by intention-to-treat analysis evaluating on-treatment virologic response and SVR. Methods: HCV-1 patients were genotyped as CC, CT, or TT at the polymorphic site, rs12979860. Viral kinetics and rates of rapid virologic response (RVR, week 4), complete early virologic response (week 12), and SVR were compared by IL-28B type in 3 self-reported ethnic groups: Caucasians (n = 1171), African Americans (n = 300), and Hispanics (n = 116). Results: In Caucasians, the CC IL-28B type was associated with improved early viral kinetics and greater likelihood of RVR (28% vs 5% and 5%; P < .0001), complete early virologic response (87% vs 38% and 28%; P < .0001), and SVR (69% vs 33% and 27%; P < .0001) compared with CT and TT. A similar association occurred within African Americans and Hispanics. In a multivariable regression model, CC IL-28B type was the strongest pretreatment predictor of SVR (odds ratio, 5.2; 95% confidence interval, 4.1-6.7). RVR was a strong predictor of SVR regardless of IL-28B type. In non-RVR patients, the CC IL-28B type was associated with a higher rate of SVR (Caucasians, 66% vs 31% and 24%; P < .0001). Conclusions: In treatment-naive HCV-1 patients treated with pegylated interferon and ribavirin, a polymorphism upstream of IL-28B is associated with increased on-treatment and sustained virologic response and effectively predicts treatment outcome.

AB - Background & Aims: We recently identified a polymorphism upstream of interleukin (IL)-28B to be associated with a 2-fold difference in sustained virologic response (SVR) rates to pegylated interferon-alfa and ribavirin therapy in a large cohort of treatment-naive, adherent patients with chronic hepatitis C virus genotype 1 (HCV-1) infection. We sought to confirm the polymorphism's clinical relevance by intention-to-treat analysis evaluating on-treatment virologic response and SVR. Methods: HCV-1 patients were genotyped as CC, CT, or TT at the polymorphic site, rs12979860. Viral kinetics and rates of rapid virologic response (RVR, week 4), complete early virologic response (week 12), and SVR were compared by IL-28B type in 3 self-reported ethnic groups: Caucasians (n = 1171), African Americans (n = 300), and Hispanics (n = 116). Results: In Caucasians, the CC IL-28B type was associated with improved early viral kinetics and greater likelihood of RVR (28% vs 5% and 5%; P < .0001), complete early virologic response (87% vs 38% and 28%; P < .0001), and SVR (69% vs 33% and 27%; P < .0001) compared with CT and TT. A similar association occurred within African Americans and Hispanics. In a multivariable regression model, CC IL-28B type was the strongest pretreatment predictor of SVR (odds ratio, 5.2; 95% confidence interval, 4.1-6.7). RVR was a strong predictor of SVR regardless of IL-28B type. In non-RVR patients, the CC IL-28B type was associated with a higher rate of SVR (Caucasians, 66% vs 31% and 24%; P < .0001). Conclusions: In treatment-naive HCV-1 patients treated with pegylated interferon and ribavirin, a polymorphism upstream of IL-28B is associated with increased on-treatment and sustained virologic response and effectively predicts treatment outcome.

KW - Genetics

KW - IL-28B

KW - Interferon-Lambda

KW - Peg-Interferon-Alfa

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