Predictive Value of Interferon-Lambda Gene Polymorphisms for Treatment Response in Chronic Hepatitis C
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{"title"=>"Predictive value of interferon-lambda gene polymorphisms for treatment response in chronic hepatitis C", "type"=>"journal", "authors"=>[{"first_name"=>"Simone", "last_name"=>"Susser", "scopus_author_id"=>"24448363600"}, {"first_name"=>"Eva", "last_name"=>"Herrmann", "scopus_author_id"=>"55994026700"}, {"first_name"=>"Christian", "last_name"=>"Lange", "scopus_author_id"=>"36554496200"}, {"first_name"=>"Nabila", "last_name"=>"Hamdi", "scopus_author_id"=>"37461248800"}, {"first_name"=>"Tobias", "last_name"=>"Müller", "scopus_author_id"=>"56489405700"}, {"first_name"=>"Thomas", "last_name"=>"Berg", "scopus_author_id"=>"15833772800"}, {"first_name"=>"Dany", "last_name"=>"Perner", "scopus_author_id"=>"49964400200"}, {"first_name"=>"Stefan", "last_name"=>"Zeuzem", "scopus_author_id"=>"7103125178"}, {"first_name"=>"Christoph", "last_name"=>"Sarrazin", "scopus_author_id"=>"7004249751"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84911948122", "sgr"=>"84911948122", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0112592", "pmid"=>"25393304", "pui"=>"600507516"}, "id"=>"fb7b4681-f605-39d3-9fbc-c2f06f060bc1", "abstract"=>"BACKGROUND: IL28B gene polymorphism is the best baseline predictor of response to interferon alfa-based antiviral therapies in chronic hepatitis C. Recently, a new IFN-L4 polymorphism was identified as first potential functional variant for induction of IL28B expression. Individualization of interferon alfa-based therapies based on a combination of IL28B/IFN-L4 polymorphisms may help to optimize virologic outcome and economic resources.\\n\\nMETHODS: Optimization of treatment outcome prediction was assessed by combination of different IL28B and IFN-L4 polymorphisms in patients with chronic HCV genotype 1 (n = 385), 2/3 (n = 267), and 4 (n = 220) infection treated with pegylated interferon alfa (PEG-IFN) and ribavirin with (n = 79) or without telaprevir. Healthy people from Germany (n = 283) and Egypt (n = 96) served as controls.\\n\\nRESULTS: Frequencies of beneficial IL28B rs12979860 C/C genotypes were lower in HCV genotype 1/4 infected patients in comparison to controls (20-35% vs. 46-47%) this was also true for ss469415590 TT/TT (20-35% vs. 45-47%). Single interferon-lambda SNPs (rs12979860, rs8099917, ss469415590) correlated with sustained virologic response (SVR) in genotype 1, 3, and 4 infected patients while no association was observed for genotype 2. Interestingly, in genotype 3 infected patients, best SVR prediction was based on IFN-L4 genotype. Prediction of SVR with high accuracy (71-96%) was possible in genotype 1, 2, 3 and 4 infected patients who received PEG-IFN/ribavirin combination therapy by selection of beneficial IL28B rs12979860 C/C and/or ss469415590 TT/TT genotypes (p<0.001). For triple therapy with first generation protease inhibitors (PIs) (boceprevir, telaprevir) prediction of high SVR (90%) rates was based on the presence of at least one beneficial genotype of the 3 IFN-lambda SNPs.\\n\\nCONCLUSION: IFN-L4 seems to be the best single predictor of SVR in genotype 3 infected patients. For optimized prediction of SVR by treatment with dual combination or first generation PI triple therapies, grouping of interferon-lambda haplotypes may be helpful with positive predictive values of 71-96%.", "link"=>"http://www.mendeley.com/research/predictive-value-interferonlambda-gene-polymorphisms-treatment-response-chronic-hepatitis-c-3", "reader_count"=>12, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Researcher"=>3, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Researcher"=>3, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>4, "Agricultural and Biological Sciences"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>4}}, "reader_count_by_country"=>{"United Kingdom"=>1}, "group_count"=>2}

Scopus | Further Information

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  • {"files"=>["https://ndownloader.figshare.com/files/1793328"], "description"=>"<p>A-2E: SVR prediction rates in HCV infected patients based on interferon-lambda host genotypes and grouping of such by applying a binary regression tree analysis. <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0112592#pone-0112592-g002\" target=\"_blank\">Figure 2A</a>: HCV genotype 1 patients treated with dual-therapy (PEG-IFN/RBV). <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0112592#pone-0112592-g002\" target=\"_blank\">Figure 2B</a>: HCV genotype 1 patients treated with triple-therapy (TVR/PEG-IFN/RBV). <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0112592#pone-0112592-g002\" target=\"_blank\">Figure 2C</a>: HCV genotype 2 patients. <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0112592#pone-0112592-g002\" target=\"_blank\">Figure 2D</a>: HCV genotype 3 patients. <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0112592#pone-0112592-g002\" target=\"_blank\">Figure 2E</a>: HCV genotype 4 patients. The boxes show the proportion of the CC+TT+TT/TT haplotype in all patients having rs12979860 CC, rs8099917 TT, and ss469415590 TT/TT, respectively.</p>", "links"=>[], "tags"=>["IL 28B expression", "combination", "genotype 3", "therapy", "svr", "HCV genotype 1", "pi", "snp", "treatment outcome prediction", "pegylated interferon alfa", "generation protease inhibitors", "tt", "Chronic Hepatitis C BackgroundIL 28B gene polymorphism", "IL 28B polymorphisms"], "article_id"=>1240638, "categories"=>["Biological Sciences"], "users"=>["Simone Susser", "Eva Herrmann", "Christian Lange", "Nabila Hamdi", "Tobias Müller", "Thomas Berg", "Dany Perner", "Stefan Zeuzem", "Christoph Sarrazin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112592.g002", "stats"=>{"downloads"=>0, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Predictive_Value_of_Interferon_Lambda_Gene_Polymorphisms_for_Treatment_Response_in_Chronic_Hepatitis_C_Figure_2_/1240638", "title"=>"Predictive Value of Interferon-Lambda Gene Polymorphisms for Treatment Response in Chronic Hepatitis C - Figure 2", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-13 03:59:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/1793339"], "description"=>"<p>GT – genotype; BL – baseline; CI – confidence interval; n. s. – not significant.</p><p>Multivariate logistic regression of baseline predictors (age, HCV RNA concentration, liver fibrosis, <i>IL28B</i> rs12979860 CC and rs8099917 TT genotype, and <i>IFN-L4</i> ss469415590 TT/TT genotype) in genotype 1 infected patients.</p>", "links"=>[], "tags"=>["IL 28B expression", "combination", "genotype 3", "therapy", "svr", "HCV genotype 1", "pi", "snp", "treatment outcome prediction", "pegylated interferon alfa", "generation protease inhibitors", "tt", "Chronic Hepatitis C BackgroundIL 28B gene polymorphism", "IL 28B polymorphisms"], "article_id"=>1240649, "categories"=>["Biological Sciences"], "users"=>["Simone Susser", "Eva Herrmann", "Christian Lange", "Nabila Hamdi", "Tobias Müller", "Thomas Berg", "Dany Perner", "Stefan Zeuzem", "Christoph Sarrazin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112592.t004", "stats"=>{"downloads"=>4, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Multivariate_logistic_regression_of_baseline_predictors_age_HCV_RNA_concentration_liver_fibrosis_IL28B_rs12979860_CC_and_rs8099917_TT_genotype_and_IFN_L4_ss469415590_TT_TT_genotype_in_genotype_1_infected_patients_/1240649", "title"=>"Multivariate logistic regression of baseline predictors (age, HCV RNA concentration, liver fibrosis, <i>IL28B</i> rs12979860 CC and rs8099917 TT genotype, and <i>IFN-L4</i> ss469415590 TT/TT genotype) in genotype 1 infected patients.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-13 03:59:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/1793337"], "description"=>"<p>GT1 (d) – HCV genotype 1 infected patients receiving dual-therapy (PEG-INF + Ribavirin); GT1 (t) – HCV genotype 1 infected patients receiving triple-therapy (TPR + PEG-INF + Ribavirin).</p><p>GT – genotype; BL – baseline; n.a. – not applicable.</p>1<p>p-values from Wilcoxon-Mann-Whitney-U-test, Kruskal-Wallis-test and χ2 test for quantitative and categorical predictors, respectively.</p><p>Predictors of sustained virologic response (age, HCV RNA concentration, liver fibrosis, <i>IL28B</i> rs12979860 CC and rs8099917 TT genotype, and <i>IFN-L4</i> ss469415590 TT/TT genotype) in genotype 1, 2, and 3 infected patients.</p>", "links"=>[], "tags"=>["IL 28B expression", "combination", "genotype 3", "therapy", "svr", "HCV genotype 1", "pi", "snp", "treatment outcome prediction", "pegylated interferon alfa", "generation protease inhibitors", "tt", "Chronic Hepatitis C BackgroundIL 28B gene polymorphism", "IL 28B polymorphisms"], "article_id"=>1240647, "categories"=>["Biological Sciences"], "users"=>["Simone Susser", "Eva Herrmann", "Christian Lange", "Nabila Hamdi", "Tobias Müller", "Thomas Berg", "Dany Perner", "Stefan Zeuzem", "Christoph Sarrazin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112592.t003", "stats"=>{"downloads"=>5, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Predictors_of_sustained_virologic_response_age_HCV_RNA_concentration_liver_fibrosis_IL28B_rs12979860_CC_and_rs8099917_TT_genotype_and_IFN_L4_ss469415590_TT_TT_genotype_in_genotype_1_2_and_3_infected_patients_/1240647", "title"=>"Predictors of sustained virologic response (age, HCV RNA concentration, liver fibrosis, <i>IL28B</i> rs12979860 CC and rs8099917 TT genotype, and <i>IFN-L4</i> ss469415590 TT/TT genotype) in genotype 1, 2, and 3 infected patients.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-13 03:59:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/1793333"], "description"=>"<p>GT1(d), HCV genotype 1 infected patients receiving dual-therapy (PEG-IFN + ribavirin); GT1(t), HCV genotype 1 infected patients receiving triple-therapy (TVR+PEG-IFN + ribavirin).</p><p>GT, genotype.</p><p>SVR, sustained virologic response.</p><p>n. a., not applicable.</p><p>Virologic and histological characteristics of patients infected with HCV genotype 1 (dual and triple therapy), 2, 3, and 4.</p>", "links"=>[], "tags"=>["IL 28B expression", "combination", "genotype 3", "therapy", "svr", "HCV genotype 1", "pi", "snp", "treatment outcome prediction", "pegylated interferon alfa", "generation protease inhibitors", "tt", "Chronic Hepatitis C BackgroundIL 28B gene polymorphism", "IL 28B polymorphisms"], "article_id"=>1240643, "categories"=>["Biological Sciences"], "users"=>["Simone Susser", "Eva Herrmann", "Christian Lange", "Nabila Hamdi", "Tobias Müller", "Thomas Berg", "Dany Perner", "Stefan Zeuzem", "Christoph Sarrazin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112592.t001", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Virologic_and_histological_characteristics_of_patients_infected_with_HCV_genotype_1_dual_and_triple_therapy_2_3_and_4_/1240643", "title"=>"Virologic and histological characteristics of patients infected with HCV genotype 1 (dual and triple therapy), 2, 3, and 4.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-13 03:59:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/1793332"], "description"=>"<p>VLwk4 – HCV RNA concentration at week 4 under therapy Score – includes the baseline parameters: age, HCV RNA concentration at baseline, fibrosis stage, rs12979869 C/C, rs8099917 T/T, and ss469415590 TT/TT.</p>", "links"=>[], "tags"=>["IL 28B expression", "combination", "genotype 3", "therapy", "svr", "HCV genotype 1", "pi", "snp", "treatment outcome prediction", "pegylated interferon alfa", "generation protease inhibitors", "tt", "Chronic Hepatitis C BackgroundIL 28B gene polymorphism", "IL 28B polymorphisms"], "article_id"=>1240642, "categories"=>["Biological Sciences"], "users"=>["Simone Susser", "Eva Herrmann", "Christian Lange", "Nabila Hamdi", "Tobias Müller", "Thomas Berg", "Dany Perner", "Stefan Zeuzem", "Christoph Sarrazin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112592.g003", "stats"=>{"downloads"=>5, "page_views"=>165, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Results_of_the_Delong_test_for_comparison_of_ROC_curves_paired_were_as_follows_Test_1_VLwk4_AUC_8202_8202_0_793653_SD_8202_8202_0_025563_CI_8202_8202_0_743552_0_843755_Test_2_Score_AUC_8202_8202_0_729519_SD_8202_8202_0_028006_CI_8202_8202_0_674629_0_7844/1240642", "title"=>"Results of the Delong-test for comparison of ROC-curves (paired) were as follows: Test 1 (VLwk4): AUC = 0.793653, SD = 0.025563, CI = [0.743552; 0.843755]; Test 2 (Score): AUC = 0.729519, SD = 0.028006, CI = [0.674629; 0.784410].", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-13 03:59:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/1793341"], "description"=>"<p>Calculation is based on HCV genotype 1, 2, and 3 infected patients with available data on ALT, HCV RNA concentration and fibrosis stage. P-values are from Wilcoxon-Mann-Whitney-U-test and are not corrected for multiple testing.</p><p>Correlation of biochemical, virologic and histological parameters of genotype 1 (n = 371 dual and n = 81 triple therapy) and 2/3 (n = 198) infected patients with rs12979860, rs8099917, and ss469415590 genotypes.</p>", "links"=>[], "tags"=>["IL 28B expression", "combination", "genotype 3", "therapy", "svr", "HCV genotype 1", "pi", "snp", "treatment outcome prediction", "pegylated interferon alfa", "generation protease inhibitors", "tt", "Chronic Hepatitis C BackgroundIL 28B gene polymorphism", "IL 28B polymorphisms"], "article_id"=>1240651, "categories"=>["Biological Sciences"], "users"=>["Simone Susser", "Eva Herrmann", "Christian Lange", "Nabila Hamdi", "Tobias Müller", "Thomas Berg", "Dany Perner", "Stefan Zeuzem", "Christoph Sarrazin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112592.t005", "stats"=>{"downloads"=>5, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Correlation_of_biochemical_virologic_and_histological_parameters_of_genotype_1_n_8202_8202_371_dual_and_n_8202_8202_81_triple_therapy_and_2_3_n_8202_8202_198_infected_patients_with_rs12979860_rs8099917_and_ss469415590_genotypes_/1240651", "title"=>"Correlation of biochemical, virologic and histological parameters of genotype 1 (n = 371 dual and n = 81 triple therapy) and 2/3 (n = 198) infected patients with rs12979860, rs8099917, and ss469415590 genotypes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-13 03:59:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/1793324"], "description"=>"<p>Frequencies of interferon-lambda genotypes in different patient and control cohorts.</p>", "links"=>[], "tags"=>["IL 28B expression", "combination", "genotype 3", "therapy", "svr", "HCV genotype 1", "pi", "snp", "treatment outcome prediction", "pegylated interferon alfa", "generation protease inhibitors", "tt", "Chronic Hepatitis C BackgroundIL 28B gene polymorphism", "IL 28B polymorphisms"], "article_id"=>1240636, "categories"=>["Biological Sciences"], "users"=>["Simone Susser", "Eva Herrmann", "Christian Lange", "Nabila Hamdi", "Tobias Müller", "Thomas Berg", "Dany Perner", "Stefan Zeuzem", "Christoph Sarrazin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112592.g001", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Frequencies_of_interferon_lambda_genotypes_in_different_patient_and_control_cohorts_/1240636", "title"=>"Frequencies of interferon-lambda genotypes in different patient and control cohorts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-13 03:59:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/1793335"], "description"=>"<p>GT1(d) – HCV genotype 1 infected patients receiving dual-therapy (PEG-INF + Ribavirin); GT1(t) – HCV genotype 1 infected patients receiving triple-therapy (TPR + PEG-INF + Ribavirin); <sup>1</sup>p-value from χ2 test; <sup>2</sup>p-value from Fisher-Freeman-Halton’s exact test.</p><p>Frequencies of <i>IFN-L4</i> and <i>IFN-L3</i> genotypes (ss469415590, rs12979860, rs8099917) in HCV genotype 1, 2, 3, and 4 infected patients and different treatment outcomes.</p>", "links"=>[], "tags"=>["IL 28B expression", "combination", "genotype 3", "therapy", "svr", "HCV genotype 1", "pi", "snp", "treatment outcome prediction", "pegylated interferon alfa", "generation protease inhibitors", "tt", "Chronic Hepatitis C BackgroundIL 28B gene polymorphism", "IL 28B polymorphisms"], "article_id"=>1240645, "categories"=>["Biological Sciences"], "users"=>["Simone Susser", "Eva Herrmann", "Christian Lange", "Nabila Hamdi", "Tobias Müller", "Thomas Berg", "Dany Perner", "Stefan Zeuzem", "Christoph Sarrazin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112592.t002", "stats"=>{"downloads"=>3, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Frequencies_of_IFN_L4_and_IFN_L3_genotypes_ss469415590_rs12979860_rs8099917_in_HCV_genotype_1_2_3_and_4_infected_patients_and_different_treatment_outcomes_/1240645", "title"=>"Frequencies of <i>IFN-L4</i> and <i>IFN-L3</i> genotypes (ss469415590, rs12979860, rs8099917) in HCV genotype 1, 2, 3, and 4 infected patients and different treatment outcomes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-13 03:59:24"}

PMC Usage Stats | Further Information

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Relative Metric

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