Evidence map›Paper›PMID 30723271›Full record

ArticleScientific reports2019

A variant in the MICA gene is associated with liver fibrosis progression in chronic hepatitis C through TGF-β1 dependent mechanisms.

Rasha El Sharkawy, Ali Bayoumi, Mayada Metwally, Alessandra Mangia, Thomas Berg, Manuel Romero-Gomez, Maria Lorena Abate, William L Irving, David Sheridan, Gregory J Dore and 23 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
0.3field-weighted citation impact, top 42% 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, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. Pooled it
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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

33 authors at 16 institutions in 7 countries.

Rasha El SharkawyStorr Liver Centre, The Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, and Westmead Hospital NSW, Sydney, Australia.
Ali BayoumiStorr Liver Centre, The Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, and Westmead Hospital NSW, Sydney, Australia.
Mayada MetwallyStorr Liver Centre, The Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, and Westmead Hospital NSW, Sydney, 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.
Manuel Romero-GomezUnit for The Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario Virgen del Rocío, University of Seville, Sevilla, Spain.ORCID 0000-0001-8494-8947
Maria Lorena AbateDivision of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, Turin, Italy.
William L IrvingNIHR Biomedical Research Unit in Gastroenterology and the Liver, University of Nottingham, Nottingham, United Kingdom.
David SheridanInstitute of Translational and Stratified Medicine, Plymouth University, Plymouth, United Kingdom.ORCID 0000-0001-5100-814X
Gregory J DoreKirby Institute, The University of New South Wales, Sydney, NSW, Australia.
Ulrich SpenglerDepartment of Internal Medicine I, University of Bonn, Bonn, Germany.
Pietro LamperticoUniversità degli Studi di Milano Centro A.M. e A. Migliavacca, First Division of Gastroenterology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation Milan Italy, Milan, Italy.
Elisabetta BugianesiDivision of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, Turin, Italy.
Martin WeltmanDepartment of Gastroenterology and Hepatology, Nepean Hospital, Sydney, NSW, Australia.
Lindsay MollisonDepartment of Gastroenterology and Hepatology, Fremantle Hospital, Fremantle, WA, Australia.
Wendy ChengDepartment of Gastroenterology & Hepatology, Royal Perth Hospital, Wellington, WA, Australia.
Stephen RiordanGastrointestinal and Liver Unit, Prince of Wales Hospital and University of New South Wales, Sydney, NSW, Australia.
Rosanna SantoroDivision of Hepatology, Ospedale Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo, Italy.
Rocío Gallego-DuránUnit for The Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario Virgen del Rocío, University of Seville, Sevilla, Spain.
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.
Roberta D'AmbrosioUniversità degli Studi di Milano Centro A.M. e A. Migliavacca, First Division of Gastroenterology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation Milan Italy, Milan, Italy.
Duncan McLeodDepartment of Anatomical Pathology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Sydney, Australia.
Elizabeth PowellThe University of Queensland, School of Medicine, Princess Alexandra Hospital, Woolloongabba, QLD, Australia.
Olivier LatchoumaninStorr Liver Centre, The Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, and Westmead Hospital NSW, Sydney, Australia.
Khaled ThabetStorr Liver Centre, The Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, and Westmead Hospital NSW, Sydney, Australia.
Mustafa A M NajimStorr Liver Centre, The Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, and Westmead Hospital NSW, Sydney, Australia.
Mark W DouglasStorr Liver Centre, The Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, and Westmead Hospital NSW, Sydney, Australia.ORCID 0000-0003-4621-3485
Christopher LiddleStorr Liver Centre, The Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, and Westmead Hospital NSW, Sydney, Australia.ORCID 0000-0003-3936-6790
Liang QiaoStorr Liver Centre, The Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, and Westmead Hospital NSW, Sydney, Australia.ORCID 0000-0002-9627-4887
Jacob GeorgeStorr Liver Centre, The Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, and Westmead Hospital NSW, Sydney, Australia. jacob.george@sydney.edu.au.
Mohammed EslamStorr Liver Centre, The Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, and Westmead Hospital NSW, Sydney, Australia.
International Liver Disease Genetics Consortium (ILDGC)
The University of Sydney · AUUNSW Sydney · AUHospital Universitario Virgen del Rocío · ESUniversity Hospital Leipzig · DEUniversity of Turin · ITCasa Sollievo della Sofferenza · ITFremantle Hospital · AUUniversity of Bonn · DEUniversity of Milan · ITUniversity of Plymouth · GBNepean Hospital · AUNewcastle University · GBRoyal Perth Hospital · AUThe University of Queensland · AUUniversity of Nottingham · GBWestmead Hospital · AU

Funding

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

Abstract

Hepatocarcinogenesis is tightly linked to liver fibrosis. Recently, two GWAS variants, MICA rs2596542 and DEPDC5 rs1012068 were identified as being associated with the development of HCV-induced hepatocellular carcinoma (HCC) in Japanese patients. The role of these variants on hepatic inflammation and fibrosis that are closely associated with HCC development is not known, nor are the biological mechanisms underlying their impact on the liver. Here, we demonstrate in 1689 patients with chronic hepatitis C (CHC) (1,501 with CHC and 188 with HCV-related HCC), that the MICA (T) allele, despite not being associated with HCC susceptibility, is associated with increased fibrosis stage (OR: 1.47, 95% CI: 1.05-2.06, p = 0.02) and fibrosis progression rate (hazards ratio: 1.41, 95% CI: 1.04-1.90, p = 0.02). The DEPDC5 variant was not associated with any of these phenotypes. MICA expression was down-regulated in advanced fibrosis stages. Further, (T) allele carriage was associated with lower MICA expression in liver and serum. Transforming growth factor-β1 (TGF-β1) expression suppresses MICA expression in hepatic stellate cells. Our findings suggest a novel mechanism linking susceptibility to advanced fibrosis and subsequently indirectly to HCC, to the level of MICA expression through TGF-β1-dependent mechanisms.

Indexed as

Polymorphism, Single NucleotideFemaleGTPase-Activating ProteinsHepatitis C, ChronicHistocompatibility Antigens Class IHumansLiverLiver CirrhosisMaleSignal TransductionTransforming Growth Factor beta1DEPDC5 protein, humanGTPase-Activating ProteinsHistocompatibility Antigens Class IMHC class I-related chain ATransforming Growth Factor beta1

Identifiers

PMID30723271
PMCPMC6363805
OpenAlexW2912816320

What OpenQuestion holds

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LicenceCC BY
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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.