Evidence map›Paper›PMID 24335707›Full record

ArticleGenes and immunity2014

Hepatic metallothionein expression in chronic hepatitis C virus infection is IFNL3 genotype-dependent.

K S O'Connor, G Parnell, E Patrick, G Ahlenstiel, V Suppiah, D van der Poorten, S A Read, R Leung, M W Douglas, J Y H Yang and 4 more

Abstract read
PubMed Publisher
In one paragraph

Article in Genes and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.6field-weighted citation impact, top 30% 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

13 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. The Role of Zinc in Antiviral Immunity.Advances in nutrition (Bethesda, Md.) · 2019
    Review
  9. Metallothioneins: Emerging Modulators in Immunity and Infection.International journal of molecular sciences · 2017
    Review
  10. Article
  11. Article
  12. Article
  13. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

K S O'ConnorInstitute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.
G ParnellInstitute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.
E PatrickDepartment of Mathematics, University of Sydney, Sydney, New South Wales, Australia.
G AhlenstielStorr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia.
V Suppiah1] Institute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia [2] Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia.
D van der PoortenStorr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia.
S A Read1] Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia [2] Centre for Infectious Diseases and Microbiology, Sydney Emerging infections and Biosecurity Institute, University of Sydney and Westmead Hospital, Sydney, New South Wales, Australia.
R Leung1] Institute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia [2] Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia.
M W Douglas1] Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia [2] Centre for Infectious Diseases and Microbiology, Sydney Emerging infections and Biosecurity Institute, University of Sydney and Westmead Hospital, Sydney, New South Wales, Australia.
J Y H YangDepartment of Mathematics, University of Sydney, Sydney, New South Wales, Australia.
G J StewartInstitute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.
C LiddleStorr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia.
J GeorgeStorr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia.
D R BoothInstitute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.
The University of Sydney · AUWestmead Hospital · AUWestmead Institute · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The IFNL3 genotype predicts the clearance of hepatitis C virus (HCV), spontaneously and with interferon (IFN)-based therapy. The responder genotype is associated with lower expression of interferon stimulated genes (ISGs) in liver biopsies from chronic hepatitis C patients. However, ISGs represent many interacting molecular pathways, and we hypothesised that the IFNL3 genotype may produce a characteristic pattern of ISG expression explaining the effect of genotype on viral clearance. For the first time, we identified an association between a cluster of ISGs, the metallothioneins (MTs) and IFNL3 genotype. Importantly, MTs were significantly upregulated (in contrast to most other ISGs) in HCV-infected liver biopsies of rs8099917 responders. An association between lower fibrosis scores and higher MT levels was demonstrated underlying clinical relevance of this association. As expected, overall ISGs were significantly downregulated in biopsies from subjects with the IFNL3 rs8099917 responder genotype (P=2.38 × 10(-7)). Peripheral blood analysis revealed paradoxical and not previously described findings with upregulation of ISGs seen in the responder genotype (P=1.00 × 10(-4)). The higher MT expression in responders may contribute to their improved viral clearance and MT-inducing agents may be useful adjuncts to therapy for HCV. Upregulation of immune cell ISGs in responders may also contribute to the IFNL3 genotype effect.

Indexed as

GenotypeHepacivirusHepatitis C, ChronicHumansInterferon-alphaInterferon LambdaInterferon Regulatory FactorsInterferonsInterleukinsLiverLiver CirrhosisMetallothioneinPolyethylene GlycolsPolymorphism, Single NucleotideRecombinant ProteinsRibavirinInterferon-alphaInterferon Lambdainterferon-lambda, humanInterferon Regulatory FactorsInterferonsInterleukinsMetallothioneinpeginterferon alfa-2aPolyethylene GlycolsRecombinant ProteinsRibavirin

Identifiers

PMID24335707
OpenAlexW2105446849

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.