ArticlePloS one2014
Predictive value of interferon-lambda gene polymorphisms for treatment response in chronic hepatitis C.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Contemporary Insights into Hepatitis C Virus: A Comprehensive Review.Microorganisms · 2024Review
- The Prevalence of Pharmacogenomics Variants and Their Clinical Relevance Among the Pakistani Population.Evolutionary bioinformatics online · 2022Article
- HCV-related liver and lymphoproliferative diseases: association with polymorphisms of IL28B and TLR2.Oncotarget · 2016Article
- Microbial pathogenesis and type III interferons.Cytokine & growth factor reviews · 2016Review
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- IFN-λ: A New Inducer of Local Immunity against Cancer and Infections.Frontiers in immunology · 2016Review
- Immunopathogenesis of Hepatitis C Virus Infection.Gastroenterology clinics of North America · 2015Review
- Interferon Lambda 4 Polymorphism Predicts Sustained Viral Response in Hepatitis C Virus Patients Irrespective of Hepatitis C Virus Genotypes, Ethnicity or Treatment Regimen: Results From a Meta-Analysis.Hepatitis monthly · 2015Review
- Duplex High-Resolution Melting Assay for the Simultaneous Genotyping of IL28B rs12979860 and PNPLA3 rs738409 Polymorphisms in Chronic Hepatitis C Patients.International journal of molecular sciences · 2015Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIL28B 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.
methodsOptimization 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.
resultsFrequencies 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.
conclusionIFN-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%.
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