Evidence map›Paper›PMID 28394349›Full record

ArticleNature genetics2017

IFN-λ3, not IFN-λ4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis.

Mohammed Eslam, Duncan McLeod, Kebitsaone Simon Kelaeng, Alessandra Mangia, Thomas Berg, Khaled Thabet, William L Irving, Gregory J Dore, David Sheridan, Henning Grønbæk and 19 more

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Nature genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
10.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 96 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Macrophage heterogeneity in liver fibrosis.Frontiers in immunology · 2025
    Review
  8. Frequencies of anInternational journal of molecular sciences · 2024
    Article
  9. Review
  10. Review
  11. IFN-λ3 is induced byInfection and immunity · 2024
    Article
  12. Interferon-λ3 rs12979860 can regulate inflammatory cytokines production in pulmonary fibrosis.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023
    Article
  13. Review
  14. Article
  15. Review
  16. Biomarkers of Metabolic (Dysfunction)-associated Fatty Liver Disease: An Update.Journal of clinical and translational hepatology · 2022
    Review
  17. Article
  18. Article
  19. Update on genetics and epigenetics in metabolic associated fatty liver disease.Therapeutic advances in endocrinology and metabolism · 2022
    Review
  20. The Impact of IFNλ4 on the Adaptive Immune Response to SARS-CoV-2 Infection.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2021
    Article

2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors at 16 institutions in 7 countries.

Mohammed EslamStorr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia.
Duncan McLeodDepartment of Anatomical Pathology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Sydney, New South Wales, Australia.
Kebitsaone Simon KelaengStorr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia.
Alessandra MangiaDivision of Hepatology, Ospedale Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo, Italy.
Thomas BergSection of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig, Germany.
Khaled ThabetStorr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia.
William L IrvingNIHR Biomedical Research Unit in Gastroenterology and the Liver, University of Nottingham, Nottingham, UK.
Gregory J DoreKirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
David SheridanInstitute of Translational and Stratified Medicine, Plymouth University, Plymouth, UK.
Henning GrønbækDepartment of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
Maria Lorena AbateDivision of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, Turin, Italy.
Rune HartmannDepartment of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0003-1159-066X
Elisabetta BugianesiDivision of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, Turin, Italy.
Ulrich SpenglerDepartment of Internal Medicine I, University of Bonn, Bonn, Germany.
Angela RojasUCM IC Digestive Diseases and ciberehd. University Hospital Virgen del Rocio, Institute of Biomedicine of Seville, Seville, Spain.
David R BoothInstitute of Immunology and Allergy Research, Westmead Hospital and Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.
Martin WeltmanDepartment of Gastroenterology and Hepatology, Nepean Hospital, Sydney, New South Wales, Australia.
Lindsay MollisonDepartment of Gastroenterology and Hepatology, Fremantle Hospital, Fremantle, Western Australia, Australia.
Wendy ChengDepartment of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Western Australia, Australia.
Stephen RiordanGastrointestinal and Liver Unit, Prince of Wales Hospital and University of New South Wales, Sydney, New South Wales, Australia.
Hema MahajanDepartment of Anatomical Pathology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Sydney, New South Wales, Australia.
Janett FischerSection of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig, Germany.
Jacob NattermannDepartment of Internal Medicine I, University of Bonn, Bonn, Germany.
Mark W DouglasStorr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0003-4621-3485
Christopher LiddleStorr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia.
Elizabeth PowellUniversity of Queensland, School of Medicine, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.
Manuel Romero-GomezUCM IC Digestive Diseases and ciberehd. University Hospital Virgen del Rocio, Institute of Biomedicine of Seville, Seville, Spain.
Jacob GeorgeStorr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia.
International Liver Disease Genetics Consortium (ILDGC)
The University of Sydney · AUInstituto de Biomedicina de Sevilla · ESUniversity Hospital Leipzig · DEUniversity of Bonn · DEUniversity of Turin · ITUNSW Sydney · AUWestmead Hospital · AUAarhus University · DKAarhus University Hospital · DKCasa Sollievo della Sofferenza · ITFremantle Hospital · AUNepean Hospital · AURoyal Perth Hospital · AUThe University of Queensland · AUUniversity of Nottingham · GBUniversity of Plymouth · GB

Funding

Medical Research Council MR/N005953/1
6 · The paper itself

Abstract

Genetic variation in the IFNL3-IFNL4 (interferon-λ3-interferon-λ4) region is associated with hepatic inflammation and fibrosis. Whether IFN-λ3 or IFN-λ4 protein drives this association is not known. We demonstrate that hepatic inflammation, fibrosis stage, fibrosis progression rate, hepatic infiltration of immune cells, IFN-λ3 expression, and serum sCD163 levels (a marker of activated macrophages) are greater in individuals with the IFNL3-IFNL4 risk haplotype that does not produce IFN-λ4, but produces IFN-λ3. No difference in these features was observed according to genotype at rs117648444, which encodes a substitution at position 70 of the IFN-λ4 protein and reduces IFN-λ4 activity, or between patients encoding functionally defective IFN-λ4 (IFN-λ4-Ser70) and those encoding fully active IFN-λ4-Pro70. The two proposed functional variants (rs368234815 and rs4803217) were not superior to the discovery SNP rs12979860 with respect to liver inflammation or fibrosis phenotype. IFN-λ3 rather than IFN-λ4 likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis.

Indexed as

HaplotypesFibrosisGene FrequencyGenotypeHepacivirusHepatitis CHumansInflammationInterferon LambdaInterferonsInterleukinsLinkage DisequilibriumLiverLogistic ModelsMultivariate AnalysisPolymorphism, Single NucleotideIFNL4 protein, humanInterferon Lambdainterferon-lambda, humanInterferonsInterleukins

Identifiers

PMID28394349
OpenAlexW2605919588

What OpenQuestion holds

Textmetadata
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Registered trials

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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.