Relationship between SNPs in the IL28B region and amino acid substitutions in HCV core region in Japanese patients with chronic hepatitis C

万利子, 小林; 文孝, 鈴木; 憲夫, 芥田; 義之, 鈴木; ひとみ, 瀬崎; 寛美, 八辻; 哲也, 保坂; 正宏, 小林; 裕介, 川村; 美晴, 平川; 康司, 荒瀬; 健次, 池田; 理恵, 峰田; 里美, 岩崎; 祥予, 綿引; 祐輔, 中村; 一彰, 茶山; 博光, 熊田

doi:10.2957/kanzo.51.322

Cited by 3 publications

(1 citation statement)

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“…A previous study reported that the percentage of patients with the mutant‐type AA at residue 70 of the HCV core region increases with the progression of chronic hepatitis, suggesting that the mutation of AA at residue 70 (from arginine to glutamine or histidine) occurs in the natural course of chronic HCV infection [Kobayashi et al, 2010a]. Several recent studies have reported a higher prevalence of the mutant‐type AA at residue 70 in patients who have the TG/GG genotype of genetic polymorphism of rs8099917 near the IL28B gene, which is associated with an unfavorable response to the combination therapy with PEG‐IFN and ribavirin, than in patients who have the TT genotype [Abe et al, 2010; Kobayashi et al, 2010b]. These reports suggest that the mutation of AA residue 70 of the HCV core region may occur more frequently in patients with the TG/GG genotype.…”

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confidence: 99%

Antiviral combination therapy with peginterferon and ribavirin does not induce a therapeutically resistant mutation in the HCV core region regardless of genetic polymorphism near the IL28B gene

Toyoda

Kumada

Hayashi

et al. 2011

Journal of Medical Virology

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An association has been reported between genetic polymorphism near IL28B gene and the prevalence of mutation of hepatitis C virus (HCV) core region residue 70, both of which have been associated with a lack of virologic response to antiviral combination therapy with peginterferon (PEG-IFN) and ribavirin. This study investigated whether PEG-IFN/ribavirin combination therapy induces amino acid (AA) mutation at residue 70 of HCV and whether genetic polymorphism near IL28B gene affects it. AA substitutions at residue 70 of the HCV core region were measured and compared before and after combination therapy in 65 non-responders and 88 relapsers to the combination therapy. In three patients in whom both wild-type AA (arginine) and mutant-type AA (glutamine or histidine) were detected at residue 70 before treatment, only mutant-type AA was identified after treatment. In two patients who had wild-type AA solely before treatment, both wild-type and mutant-type AAs were identified at residue 70 after treatment. In five patients, in whom the AA had changed at residue 70 between before and after treatment, four patients carried the TT genotype at a polymorphic locus (rs8099917) near the IL28B gene and one carried the TG/GG genotype. No difference was found in the prevalence of this change of AA at residue 70 between the TT and the TG/GG genotype. Antiviral combination therapy with PEG-IFN and ribavirin does not appear to induce mutation of HCV core region residue 70 regardless of genetic polymorphism near the IL28B gene in Japanese patients infected with HCV genotype 1b.

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Section: Introductionmentioning

confidence: 99%

Antiviral combination therapy with peginterferon and ribavirin does not induce a therapeutically resistant mutation in the HCV core region regardless of genetic polymorphism near the IL28B gene

Toyoda

Kumada

Hayashi

et al. 2011

Journal of Medical Virology

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Baseline factors and early viral response (week 4) to antiviral therapy with peginterferon and ribavirin for predicting sustained virologic response in patients infected with hepatitis C virus genotype 1: A multicenter study

Toyoda

Kumada

Shimada

et al. 2012

Journal of Medical Virology

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Both baseline predictive factors and viral response at week 4 of therapy are reported to have high predictive ability for sustained virologic response to peginterferon and ribavirin combination therapy in patients with hepatitis C virus (HCV) genotype 1. However, it is not clear how these baseline variables and week 4 response should be combined to predict sustained virologic response. In this multicenter study, the authors investigated the impact of baseline predictive factors on the predictive value of week 4 viral response. Receiver-operating characteristic curve analyses were performed to evaluate the ability of week 4 reduction in HCV RNA levels to predict sustained virologic response in 293 Japanese patients infected with HCV genotype 1b. Analyses were performed in all patients and in patient subgroups stratified according to baseline variables. Overall, week 4 viral reduction demonstrates a high predictive ability for sustained virologic response. The sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy were higher than those of viral reduction at week 12. However, the best cut-off levels differ depending on the baseline factors and they were lower in patients with unfavorable baseline predictors. When patients had the TG/GG rs8099917 genotype, the best cut-off was markedly low with low PPV. Week 4 viral response can be a predictor of sustained virologic response in patients with HCV genotype 1 and is better than week 12 viral response. However, the cut-off levels should be modified based on the baseline predictive variables.

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Relevance of the Core 70 and IL-28B polymorphism and response-guided therapy of peginterferon alfa-2a ± ribavirin for chronic hepatitis C of Genotype 1b: a multicenter randomized trial, ReGIT-J study

et al. 2013

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BackgroundWe conducted a multicenter randomized clinical trial to determine the optimal treatment strategy against chronic hepatitis C virus (HCV) with genotype 1b and a high viral load (G1b/high).MethodsThe study subjects included 153 patients with G1b/high. Patients were initially treated with PEG-IFNα-2a alone and then randomly assigned to receive different treatment regimens. Ribavirin (RBV) was administered to all patients with HCV RNA at week 4. Patients negative for HCV RNA at week 4 were randomly assigned to receive PEG-IFNα-2a (group A) or PEG-IFNα-2a/RBV (group B). Patients who showed HCV RNA at week 4 but were negative at week 12 were randomly assigned to receive weekly PEG-IFNα-2a (group C) or biweekly therapy (group D). Patients who showed HCV RNA at week 12 but were negative at week 24 were randomly assigned to receive PEG-IFNα-2a/RBV (group E) or PEG-IFNα-2a/RBV/fluvastatin (group F).ResultsOverall, the rate of sustained virological response (SVR) was 46 % (70/153). The total SVR rate in the group (A, D, and F) of response-guided therapy was significantly higher than that in the group (B, C, and E) of conventional therapy [70 % (38/54) versus 52 % (32/61), p = 0.049]. Although IL28-B polymorphism and Core 70 mutation were significantly associated with efficacy, patients with rapid virological response (RVR) and complete early virological response (cEVR) achieved high SVR rates regardless of their status of IL-28B polymorphism and Core 70 mutation.ConclusionIn addition to knowing the IL-28B polymorphism and Core 70 mutation status, understanding the likelihood of virological response during treatment is critical in determining the appropriate treatment strategy.

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Relationship between SNPs in the IL28B region and amino acid substitutions in HCV core region in Japanese patients with chronic hepatitis C

Cited by 3 publications

References 4 publications

Antiviral combination therapy with peginterferon and ribavirin does not induce a therapeutically resistant mutation in the HCV core region regardless of genetic polymorphism near the IL28B gene

Antiviral combination therapy with peginterferon and ribavirin does not induce a therapeutically resistant mutation in the HCV core region regardless of genetic polymorphism near the IL28B gene

Baseline factors and early viral response (week 4) to antiviral therapy with peginterferon and ribavirin for predicting sustained virologic response in patients infected with hepatitis C virus genotype 1: A multicenter study

Relevance of the Core 70 and IL-28B polymorphism and response-guided therapy of peginterferon alfa-2a ± ribavirin for chronic hepatitis C of Genotype 1b: a multicenter randomized trial, ReGIT-J study

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