ArticleJournal of hepatology2015
Comparison of functional variants in IFNL4 and IFNL3 for association with HCV clearance.
Article in Journal of hepatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 91 citations in OpenAlex.
- Reduced ITPase activity and favorable IL28B genetic variant protect against ribavirin-induced anemia in interferon-free regimens.PloS one · 2018Trial
- Vitamin D Status and Virologic Response to HCV Therapy in the HALT-C and VIRAHEP-C Trials.PloS one · 2016Trial
- Pharmacogenomics of antibacterial and antiviral therapies: Clinical actionability, evidence gaps, and future directions.Pharmacological reviews · 2026Review
- Targets of protective immunity and opportunities in hepatitis C virus vaccine development.Nature reviews. Immunology · 2026Review
- Sex based relative expression of estrogen receptors and tumor necrosis factor-alpha in liver affects hepatitis C virus viral pathogenesis.World journal of gastroenterology · 2025Article
- Structural studies of the IFNλ4 receptor complex using cryoEM enabled by protein engineering.Nature communications · 2025Article
- Interferon Upregulation Associates with Insulin Resistance in Humans.Current diabetes reviews · 2025Review
- FURIN, IFNL4, and TLR2 gene polymorphisms in relation to COVID-19 severity: a case-control study in Egyptian patients.Infection · 2024Article
- Interferon lambda 4 is a gut antimicrobial protein.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Like a Rolling Stone? A Review on Spontaneous Clearance of Hepatitis C Virus Infection.Viruses · 2024Review
- Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Article
- No Association of IFNL4 Genotype With Opportunistic Infections and Cancers Among Men With Human Immunodeficiency Virus 1 Infection.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Article
- Polymorphisms of theFrontiers in cellular and infection microbiology · 2023Article
- The role of IFNL4 in liver inflammation and progression of fibrosis.Genes and immunity · 2022Review
- Distinct molecular phenotypes involving several human diseases are induced by IFN-λ3 and IFN-λ4 in monocyte-derived macrophages.Genes and immunity · 2022Article
- Genetic polymorphisms in thePeerJ · 2022Article
- Monocytes differentiated into macrophages and dendritic cells in the presence of human IFN-λ3 or IFN-λ4 show distinct phenotypes.Journal of leukocyte biology · 2021Article
- IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children.Genes and immunity · 2021Article
- IFN-λ4 genetic variants influence clinical malaria episodes in a cohort of Kenyan children.Malaria journal · 2021Article
- Article
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Authors and funding
14 authors at 9 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsGenetic polymorphisms within the interferon lambda (IFN-λ) region are strongly associated with hepatitis C virus (HCV) clearance; the IFNL4-ΔG/TT (rs368234815) polymorphism, which controls the generation of IFN-λ4 protein, is more strongly associated with HCV clearance than rs12979860 (the 'IL28B variant'). An IFNL3 3' untranslated region polymorphism (rs4803217) has been proposed as a causal variant that may affect HCV clearance by altering IFNL3 mRNA stability.
methodsWe compared IFNL4-ΔG/TT and rs4803217 for association with response to pegylated-IFN-α/ribavirin in the VIRAHEP-C and HALT-C trials, and spontaneous HCV clearance in the ALIVE, UHS and WIHS studies. Genotyping was performed with TaqMan assays. We compared differences in mean reduction in HCV RNA levels by genotype and haplotype. For HCV clearance, we calculated p-values comparing c-statistics for IFNL4-ΔG/TT and rs4803217 genotypes by a bootstrap approach.
resultsAmong European Americans, linkage disequilibrium between IFNL4-ΔG/TT and rs4803217 was strong (r(2)=0.89-0.99) and there were no significant differences between the variants. In African American (AA) individuals enrolled in VIRAHEP-C, HCV RNA at treatment day 28 was more strongly associated with IFNL4-ΔG/TT than rs4803217 (p=0.003); the IFNL4-ΔG:rs4803217-G haplotype, which includes the putatively favorable IFNL3 allele, was actually associated with the poorest day 28 response (p=0.03, comparison to IFNL4-ΔG:rs4803217-T haplotype). Among AA participants, associations were stronger for IFNL4-ΔG/TT than rs4803217 for undetectable HCV RNA at week 24 in Virahep-C (p=0.03) and week 20 in HALT-C (p=0.03), as well as for spontaneous HCV clearance (p=0.048).
conclusionIFNL4-ΔG/TT is the primary IFN-λ region polymorphism for impaired HCV clearance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.