ArticleHepatology (Baltimore, Md.)2009
Variants in interferon-alpha pathway genes and response to pegylated interferon-Alpha2a plus ribavirin for treatment of chronic hepatitis C virus infection in the hepatitis C antiviral long-term treatment against cirrhosis trial.
Article in Hepatology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
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- An IL28B genotype-based clinical prediction model for treatment of chronic hepatitis C.PloS one · 2011Trial
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- IFNAR2 relevance in the clinical outcome of individuals with severe COVID-19.Frontiers in immunology · 2022Article
- Progress and Challenges in the Use of a Liver-on-a-Chip for Hepatotropic Infectious Diseases.Micromachines · 2021Review
- Liver Disease: Induction, Progression, Immunological Mechanisms, and Therapeutic Interventions.International journal of molecular sciences · 2021Review
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- Congenital Zika Syndrome Is Associated With Interferon Alfa Receptor 1.Frontiers in immunology · 2021Article
- A proline deletion in IFNAR1 impairs IFN-signaling and underlies increased resistance to tuberculosis in humans.Nature communications · 2018Article
- ADAR1 polymorphisms are related to severity of liver fibrosis in HIV/HCV-coinfected patients.Scientific reports · 2017Article
- Hepatitis-C-virus-induced microRNAs dampen interferon-mediated antiviral signaling.Nature medicine · 2016Article
- Integrative role of vitamin D related and Interleukin-28B genes polymorphism in predicting treatment outcomes of Chronic Hepatitis C.BMC gastroenterology · 2016Article
- Association of symptoms and severity of rift valley fever with genetic polymorphisms in human innate immune pathways.PLoS neglected tropical diseases · 2015Article
- An RNA editor, adenosine deaminase acting on double-stranded RNA (ADAR1).Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2014Review
- Myxovirus resistance, osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B.Clinics (Sao Paulo, Brazil) · 2013Article
- The impact of ethnicity on hepatitis C virus treatment decisions and outcomes.Digestive diseases and sciences · 2013Review
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Authors and funding
22 authors at 17 institutions in 1 country.
Funding
Abstract
unlabelledCombination treatment with pegylated-interferon-alpha (PEG IFN-alpha) and ribavirin, the current recommended therapy for chronic hepatitis C virus (HCV) infection, results in a sustained virological response (SVR) in only about half of patients. Because genes involved in the interferon-alpha pathway may affect antiviral responses, we analyzed the relationship between variants in these genes and SVR among participants in the Hepatitis C Antiviral Long-Term treatment Against Cirrhosis (HALT-C) trial. Patients had advanced chronic hepatitis C that had previously failed to respond to interferon-based treatment. Participants were treated with peginterferon-alpha2a and ribavirin during the trial. Subjects with undetectable HCV RNA at week 72 were considered to have had an SVR. Subjects with detectable HCV RNA at week 20 were considered nonresponders. We used TaqMan assays to genotype 56 polymorphisms found in 13 genes in the interferon-alpha pathway. This analysis compares genotypes for participants with an SVR to nonresponders. The primary analysis was restricted to European American participants because a priori statistical power was low among the small number (n = 131) of African American patients. We used logistic regression to control the effect of other variables that are associated with treatment response. Among 581 European American patients, SVR was associated with IFNAR1 IVS1-22G (adjusted odds ratio, 0.57; P = 0.02); IFNAR2 Ex2-33C (adjusted odds ratio, 2.09; P = 0.02); JAK1 IVS22+112T (adjusted odds ratio, 1.66; P = 0.04); and ADAR Ex9+14A (adjusted odds ratio, 1.67; P = 0.03). For the TYK2-2256A promoter region variant, a borderline association was present among European American participants (OR, 1.51; P = 0.05) and a strong relationship among African American patients; all 10 with SVR who were genotyped for TYK2 -2256 carried the A variant compared with 68 of 120 (57%) nonresponders (P = 0.006).
conclusionGenetic polymorphisms in the interferon-alpha pathway may affect responses to antiviral therapy of chronic hepatitis C.
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