Insulin resistance undermines the advantages of IL28B polymorphism in the pegylated interferon alpha-2b and ribavirin treatment of chronic hepatitis C patients with genotype 1

Eiichi Ogawa, Norihiro Furusyo, Murata Masayuki, Hiroaki Ikezaki, Takeshi Ihara, Takeo Hayashi, Kazuhiro Toyoda, Hiroaki Taniai, Kyoko Okada, Mosaburo Kainuma, Jun Hayashi

研究成果: ジャーナルへの寄稿記事

31 引用 (Scopus)

抄録

Background & Aims: Recent studies have suggested that insulin resistance exerts a strong influence on chronic hepatitis C virus (HCV) infection. We analyzed pretreatment factors useful for predicting sustained virological response (SVR), especially interleukin (IL) 28B polymorphism and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Methods: This cohort study consisted of 328 chronic hepatitis C patients with HCV genotype 1 who were treated for 48 weeks with pegylated interferon (PegIFN) α-2b and ribavirin (RBV). Genotyping of the polymorphisms in the IL28B gene region (rs8099917) on chromosome 19 was performed on DNA collected from each patient. Results: No significant difference in IL28B genotype distribution was found according to HOMA-IR. Multivariate analysis identified the IL28B TT genotype (OR = 5.97, 95% CI 2.15-16.55, p = 0.0006) and the baseline HOMA-IR (OR = 0.65, 95% CI 0.48-0.87, p = 0.0044) as significant, independent pretreatment predictors of SVR. Receiver operating characteristic analyses to determine the optimal threshold values of HOMA-IR for predicting SVR showed that the areas under the curve (AUC) were high for both IL28B TT (AUC = 0.774, HOMA-IR cut-off value: 2.45) and IL28B TG/GG genotypes (AUC = 0.772, HOMA-IR cut-off value: 1.55). Conclusions: For HCV genotype 1, both IL28B and baseline HOMA-IR are independent pretreatment predictors of SVR in patients treated with PegIFNα-2b and RBV. Insulin resistance undermines the advantages of IL28B polymorphism to obtain SVR.

元の言語英語
ページ(範囲)534-540
ページ数7
ジャーナルJournal of Hepatology
57
発行部数3
DOI
出版物ステータス出版済み - 9 1 2012

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Ribavirin
Chronic Hepatitis C
Insulin Resistance
Genotype
Homeostasis
Hepacivirus
Area Under Curve
Therapeutics
Interferons
Chromosomes, Human, Pair 19
peginterferon alfa-2b
Interleukins
Virus Diseases
ROC Curve
Cohort Studies
Multivariate Analysis
DNA

All Science Journal Classification (ASJC) codes

  • Hepatology

これを引用

Insulin resistance undermines the advantages of IL28B polymorphism in the pegylated interferon alpha-2b and ribavirin treatment of chronic hepatitis C patients with genotype 1. / Ogawa, Eiichi; Furusyo, Norihiro; Masayuki, Murata; Ikezaki, Hiroaki; Ihara, Takeshi; Hayashi, Takeo; Toyoda, Kazuhiro; Taniai, Hiroaki; Okada, Kyoko; Kainuma, Mosaburo; Hayashi, Jun.

:: Journal of Hepatology, 巻 57, 番号 3, 01.09.2012, p. 534-540.

研究成果: ジャーナルへの寄稿記事

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abstract = "Background & Aims: Recent studies have suggested that insulin resistance exerts a strong influence on chronic hepatitis C virus (HCV) infection. We analyzed pretreatment factors useful for predicting sustained virological response (SVR), especially interleukin (IL) 28B polymorphism and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Methods: This cohort study consisted of 328 chronic hepatitis C patients with HCV genotype 1 who were treated for 48 weeks with pegylated interferon (PegIFN) α-2b and ribavirin (RBV). Genotyping of the polymorphisms in the IL28B gene region (rs8099917) on chromosome 19 was performed on DNA collected from each patient. Results: No significant difference in IL28B genotype distribution was found according to HOMA-IR. Multivariate analysis identified the IL28B TT genotype (OR = 5.97, 95{\%} CI 2.15-16.55, p = 0.0006) and the baseline HOMA-IR (OR = 0.65, 95{\%} CI 0.48-0.87, p = 0.0044) as significant, independent pretreatment predictors of SVR. Receiver operating characteristic analyses to determine the optimal threshold values of HOMA-IR for predicting SVR showed that the areas under the curve (AUC) were high for both IL28B TT (AUC = 0.774, HOMA-IR cut-off value: 2.45) and IL28B TG/GG genotypes (AUC = 0.772, HOMA-IR cut-off value: 1.55). Conclusions: For HCV genotype 1, both IL28B and baseline HOMA-IR are independent pretreatment predictors of SVR in patients treated with PegIFNα-2b and RBV. Insulin resistance undermines the advantages of IL28B polymorphism to obtain SVR.",
author = "Eiichi Ogawa and Norihiro Furusyo and Murata Masayuki and Hiroaki Ikezaki and Takeshi Ihara and Takeo Hayashi and Kazuhiro Toyoda and Hiroaki Taniai and Kyoko Okada and Mosaburo Kainuma and Jun Hayashi",
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T1 - Insulin resistance undermines the advantages of IL28B polymorphism in the pegylated interferon alpha-2b and ribavirin treatment of chronic hepatitis C patients with genotype 1

AU - Ogawa, Eiichi

AU - Furusyo, Norihiro

AU - Masayuki, Murata

AU - Ikezaki, Hiroaki

AU - Ihara, Takeshi

AU - Hayashi, Takeo

AU - Toyoda, Kazuhiro

AU - Taniai, Hiroaki

AU - Okada, Kyoko

AU - Kainuma, Mosaburo

AU - Hayashi, Jun

PY - 2012/9/1

Y1 - 2012/9/1

N2 - Background & Aims: Recent studies have suggested that insulin resistance exerts a strong influence on chronic hepatitis C virus (HCV) infection. We analyzed pretreatment factors useful for predicting sustained virological response (SVR), especially interleukin (IL) 28B polymorphism and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Methods: This cohort study consisted of 328 chronic hepatitis C patients with HCV genotype 1 who were treated for 48 weeks with pegylated interferon (PegIFN) α-2b and ribavirin (RBV). Genotyping of the polymorphisms in the IL28B gene region (rs8099917) on chromosome 19 was performed on DNA collected from each patient. Results: No significant difference in IL28B genotype distribution was found according to HOMA-IR. Multivariate analysis identified the IL28B TT genotype (OR = 5.97, 95% CI 2.15-16.55, p = 0.0006) and the baseline HOMA-IR (OR = 0.65, 95% CI 0.48-0.87, p = 0.0044) as significant, independent pretreatment predictors of SVR. Receiver operating characteristic analyses to determine the optimal threshold values of HOMA-IR for predicting SVR showed that the areas under the curve (AUC) were high for both IL28B TT (AUC = 0.774, HOMA-IR cut-off value: 2.45) and IL28B TG/GG genotypes (AUC = 0.772, HOMA-IR cut-off value: 1.55). Conclusions: For HCV genotype 1, both IL28B and baseline HOMA-IR are independent pretreatment predictors of SVR in patients treated with PegIFNα-2b and RBV. Insulin resistance undermines the advantages of IL28B polymorphism to obtain SVR.

AB - Background & Aims: Recent studies have suggested that insulin resistance exerts a strong influence on chronic hepatitis C virus (HCV) infection. We analyzed pretreatment factors useful for predicting sustained virological response (SVR), especially interleukin (IL) 28B polymorphism and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Methods: This cohort study consisted of 328 chronic hepatitis C patients with HCV genotype 1 who were treated for 48 weeks with pegylated interferon (PegIFN) α-2b and ribavirin (RBV). Genotyping of the polymorphisms in the IL28B gene region (rs8099917) on chromosome 19 was performed on DNA collected from each patient. Results: No significant difference in IL28B genotype distribution was found according to HOMA-IR. Multivariate analysis identified the IL28B TT genotype (OR = 5.97, 95% CI 2.15-16.55, p = 0.0006) and the baseline HOMA-IR (OR = 0.65, 95% CI 0.48-0.87, p = 0.0044) as significant, independent pretreatment predictors of SVR. Receiver operating characteristic analyses to determine the optimal threshold values of HOMA-IR for predicting SVR showed that the areas under the curve (AUC) were high for both IL28B TT (AUC = 0.774, HOMA-IR cut-off value: 2.45) and IL28B TG/GG genotypes (AUC = 0.772, HOMA-IR cut-off value: 1.55). Conclusions: For HCV genotype 1, both IL28B and baseline HOMA-IR are independent pretreatment predictors of SVR in patients treated with PegIFNα-2b and RBV. Insulin resistance undermines the advantages of IL28B polymorphism to obtain SVR.

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