An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response

Alessandra Mangia, Alexander J. Thompson, Rosanna Santoro, Valeria Piazzolla, Hans L. Tillmann, Keyur Patel, Kevin V. Shianna, Leonardo Mottola, Daniela Petruzzellis, Donato Bacca, Vito Carretta, Nicola Minerva, David B. Goldstein, John G. McHutchison

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Abstract

RESULTS: The frequencies of the IL-28B genotypes were as follows: CC, 37%; CT, 48%; and TT, 15%; 82% of patients with the CC genotype achieved a sustained virologic response (SVR), compared with 75% with the CT and 58% with the TT genotypes (P = .0046). Differences between IL-28B genotypes were greatest among patients who failed to attain RVR (VD24 SVR rates: CC, 87%; CT, 67%; and TT, 29%; P = .0002). Among patients with RVRs (61%), the IL-28B genotype was not associated with SVR (>70% for all IL-28B genotypes). In a multivariable logistic regression model, IL-28B genotype predicted SVR (odds ratio, 1.76; 95% confidence interval, 1.16-2.7).

CONCLUSIONS: An IL-28B polymorphism was associated with an SVR in patients infected with genotype 2/3 HCV who did not achieve a RVR. Analysis of IL-28B genotype might be used to guide treatment for these patients.

BACKGROUND & AIMS: Polymorphisms in the region of the interleukin (IL)-28B gene on chromosome 19 have been associated with peginterferon-alfa-induced clearance of genotype 1 hepatitis C virus (HCV); there are no data for patients with genotype 2 or 3 HCV. We evaluated the effects of IL-28B polymorphisms on response to treatment with peginterferon and ribavirin in a well-characterized cohort of genotype 2/3 patients.

METHODS: DNA was analyzed from 268 patients (Caucasian: genotype 2, 213; genotype 3, 55). Patients were randomly assigned to groups that received standard duration (24 wk; n = 68) or variable durations of therapy. Patients who received variable durations (VD) and had a rapid virologic response (RVR) were treated for 12 weeks (VD12; n = 122); those without an RVR were treated for 24 weeks (VD24; n = 78). IL-28B genotypes (rs12979860) were analyzed for association with treatment response.

Original languageEnglish
Pages (from-to)827.e1-827
JournalGastroenterology
Volume139
Issue number3
DOIs
Publication statusPublished - Sep 1 2010

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Hepacivirus
Interleukins
Genotype
Therapeutics
Logistic Models
Chromosomes, Human, Pair 19
Ribavirin
Odds Ratio
Sustained Virologic Response

ASJC Scopus subject areas

  • Medicine(all)

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An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response. / Mangia, Alessandra; Thompson, Alexander J.; Santoro, Rosanna; Piazzolla, Valeria; Tillmann, Hans L.; Patel, Keyur; Shianna, Kevin V.; Mottola, Leonardo; Petruzzellis, Daniela; Bacca, Donato; Carretta, Vito; Minerva, Nicola; Goldstein, David B.; McHutchison, John G.

In: Gastroenterology, Vol. 139, No. 3, 01.09.2010, p. 827.e1-827.

Research output: Contribution to journalArticle

Mangia, A, Thompson, AJ, Santoro, R, Piazzolla, V, Tillmann, HL, Patel, K, Shianna, KV, Mottola, L, Petruzzellis, D, Bacca, D, Carretta, V, Minerva, N, Goldstein, DB & McHutchison, JG 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, vol. 139, no. 3, pp. 827.e1-827. https://doi.org/10.1053/j.gastro.2010.05.079
Mangia, Alessandra ; Thompson, Alexander J. ; Santoro, Rosanna ; Piazzolla, Valeria ; Tillmann, Hans L. ; Patel, Keyur ; Shianna, Kevin V. ; Mottola, Leonardo ; Petruzzellis, Daniela ; Bacca, Donato ; Carretta, Vito ; Minerva, Nicola ; Goldstein, David B. ; McHutchison, John G. / An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response. In: Gastroenterology. 2010 ; Vol. 139, No. 3. pp. 827.e1-827.
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title = "An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response",
abstract = "RESULTS: The frequencies of the IL-28B genotypes were as follows: CC, 37{\%}; CT, 48{\%}; and TT, 15{\%}; 82{\%} of patients with the CC genotype achieved a sustained virologic response (SVR), compared with 75{\%} with the CT and 58{\%} with the TT genotypes (P = .0046). Differences between IL-28B genotypes were greatest among patients who failed to attain RVR (VD24 SVR rates: CC, 87{\%}; CT, 67{\%}; and TT, 29{\%}; P = .0002). Among patients with RVRs (61{\%}), the IL-28B genotype was not associated with SVR (>70{\%} for all IL-28B genotypes). In a multivariable logistic regression model, IL-28B genotype predicted SVR (odds ratio, 1.76; 95{\%} confidence interval, 1.16-2.7).CONCLUSIONS: An IL-28B polymorphism was associated with an SVR in patients infected with genotype 2/3 HCV who did not achieve a RVR. Analysis of IL-28B genotype might be used to guide treatment for these patients.BACKGROUND & AIMS: Polymorphisms in the region of the interleukin (IL)-28B gene on chromosome 19 have been associated with peginterferon-alfa-induced clearance of genotype 1 hepatitis C virus (HCV); there are no data for patients with genotype 2 or 3 HCV. We evaluated the effects of IL-28B polymorphisms on response to treatment with peginterferon and ribavirin in a well-characterized cohort of genotype 2/3 patients.METHODS: DNA was analyzed from 268 patients (Caucasian: genotype 2, 213; genotype 3, 55). Patients were randomly assigned to groups that received standard duration (24 wk; n = 68) or variable durations of therapy. Patients who received variable durations (VD) and had a rapid virologic response (RVR) were treated for 12 weeks (VD12; n = 122); those without an RVR were treated for 24 weeks (VD24; n = 78). IL-28B genotypes (rs12979860) were analyzed for association with treatment response.",
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T1 - An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response

AU - Mangia, Alessandra

AU - Thompson, Alexander J.

AU - Santoro, Rosanna

AU - Piazzolla, Valeria

AU - Tillmann, Hans L.

AU - Patel, Keyur

AU - Shianna, Kevin V.

AU - Mottola, Leonardo

AU - Petruzzellis, Daniela

AU - Bacca, Donato

AU - Carretta, Vito

AU - Minerva, Nicola

AU - Goldstein, David B.

AU - McHutchison, John G.

PY - 2010/9/1

Y1 - 2010/9/1

N2 - RESULTS: The frequencies of the IL-28B genotypes were as follows: CC, 37%; CT, 48%; and TT, 15%; 82% of patients with the CC genotype achieved a sustained virologic response (SVR), compared with 75% with the CT and 58% with the TT genotypes (P = .0046). Differences between IL-28B genotypes were greatest among patients who failed to attain RVR (VD24 SVR rates: CC, 87%; CT, 67%; and TT, 29%; P = .0002). Among patients with RVRs (61%), the IL-28B genotype was not associated with SVR (>70% for all IL-28B genotypes). In a multivariable logistic regression model, IL-28B genotype predicted SVR (odds ratio, 1.76; 95% confidence interval, 1.16-2.7).CONCLUSIONS: An IL-28B polymorphism was associated with an SVR in patients infected with genotype 2/3 HCV who did not achieve a RVR. Analysis of IL-28B genotype might be used to guide treatment for these patients.BACKGROUND & AIMS: Polymorphisms in the region of the interleukin (IL)-28B gene on chromosome 19 have been associated with peginterferon-alfa-induced clearance of genotype 1 hepatitis C virus (HCV); there are no data for patients with genotype 2 or 3 HCV. We evaluated the effects of IL-28B polymorphisms on response to treatment with peginterferon and ribavirin in a well-characterized cohort of genotype 2/3 patients.METHODS: DNA was analyzed from 268 patients (Caucasian: genotype 2, 213; genotype 3, 55). Patients were randomly assigned to groups that received standard duration (24 wk; n = 68) or variable durations of therapy. Patients who received variable durations (VD) and had a rapid virologic response (RVR) were treated for 12 weeks (VD12; n = 122); those without an RVR were treated for 24 weeks (VD24; n = 78). IL-28B genotypes (rs12979860) were analyzed for association with treatment response.

AB - RESULTS: The frequencies of the IL-28B genotypes were as follows: CC, 37%; CT, 48%; and TT, 15%; 82% of patients with the CC genotype achieved a sustained virologic response (SVR), compared with 75% with the CT and 58% with the TT genotypes (P = .0046). Differences between IL-28B genotypes were greatest among patients who failed to attain RVR (VD24 SVR rates: CC, 87%; CT, 67%; and TT, 29%; P = .0002). Among patients with RVRs (61%), the IL-28B genotype was not associated with SVR (>70% for all IL-28B genotypes). In a multivariable logistic regression model, IL-28B genotype predicted SVR (odds ratio, 1.76; 95% confidence interval, 1.16-2.7).CONCLUSIONS: An IL-28B polymorphism was associated with an SVR in patients infected with genotype 2/3 HCV who did not achieve a RVR. Analysis of IL-28B genotype might be used to guide treatment for these patients.BACKGROUND & AIMS: Polymorphisms in the region of the interleukin (IL)-28B gene on chromosome 19 have been associated with peginterferon-alfa-induced clearance of genotype 1 hepatitis C virus (HCV); there are no data for patients with genotype 2 or 3 HCV. We evaluated the effects of IL-28B polymorphisms on response to treatment with peginterferon and ribavirin in a well-characterized cohort of genotype 2/3 patients.METHODS: DNA was analyzed from 268 patients (Caucasian: genotype 2, 213; genotype 3, 55). Patients were randomly assigned to groups that received standard duration (24 wk; n = 68) or variable durations of therapy. Patients who received variable durations (VD) and had a rapid virologic response (RVR) were treated for 12 weeks (VD12; n = 122); those without an RVR were treated for 24 weeks (VD24; n = 78). IL-28B genotypes (rs12979860) were analyzed for association with treatment response.

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