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.
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 Cpatients 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.
Authors: Nikolaos K Gatselis; Kalliopi Zachou; Asterios Saitis; Maria Samara; George N Dalekos Journal: World J Gastroenterol Date: 2014-03-21 Impact factor: 5.742
Authors: María A Jiménez-Sousa; Amanda Fernández-Rodríguez; María Guzmán-Fulgencio; Mónica García-Álvarez; Salvador Resino Journal: BMC Med Date: 2013-01-08 Impact factor: 8.775