Evidence map›Paper›PMID 29357190›Full record

ArticleHepatology (Baltimore, Md.)2019

Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort.

Rachel J Church, Gerd A Kullak-Ublick, Jiri Aubrecht, Herbert L Bonkovsky, Naga Chalasani, Robert J Fontana, Jens C Goepfert, Frances Hackman, Nicholas M P King, Simon Kirby and 13 more

Open access · bronzeAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed, 4 pooled it
28.7field-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

126 citing papers in PubMed, 4 syntheses or guidelines pooled it, 234 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. [Chinese guideline for diagnosis and management of drug-induced liver injury (2023 version)].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023
    Guideline
  4. Pooled it
  5. Trial
  6. Trial
  7. Trial
  8. Trial
  9. Trial
  10. Trial
  11. Serum Hepatocyte Growth Factor Predicts Outcomes in Non-Acetaminophen Drug-Induced Acute Liver Failure.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Article
  12. Article
  13. HBV/HCV coinfection and anti-tuberculosis drug-induced liver injury: from risk assessment and exploration of mechanisms to preventive considerations.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 13 institutions in 8 countries.

Rachel J ChurchInstitute for Drug Safety Sciences, University of North Carolina at Chapel Hill, Research Triangle Park, NC.
Gerd A Kullak-UblickDepartment of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Switzerland.
Jiri AubrechtDrug Safety R&D, Pfizer Inc., Groton, CT.
Herbert L BonkovskyWake Forest University School of Medicine, Winston-Salem, NC.
Naga ChalasaniSchool of Medicine, Indiana University, Indianapolis, IN.
Robert J FontanaUniversity of Michigan, Ann Arbor, MI.
Jens C GoepfertNatural and Medical Sciences Institute, Reutlingen, Germany.
Frances HackmanPfizer Inc, New York, NY.
Nicholas M P KingPredictive Safety Testing Consortium, Tucson, AZ.
Simon KirbyPfizer Inc, New York, NY.
Patrick KirbyTakeda Pharmaceuticals, Deerfield, IL.
John MarcinakTakeda Pharmaceuticals, Deerfield, IL.
Sif OrmarsdottirGlobal Patient Safety, AstraZeneca R&D, Gothenburg, Sweden.
Shelli J SchomakerDrug Safety R&D, Pfizer Inc., Groton, CT.
Ina Schuppe-KoistinenScience for Life Laboratory, Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Francis WolenskiTakeda Pharmaceuticals, Deerfield, IL.
Nadir ArberTel Aviv Sourasky Medical Center, Tel Aviv University, Israel.
Michael MerzDepartment of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Switzerland.
John-Michael SauerPredictive Safety Testing Consortium, Tucson, AZ.
Raul J AndradeUnidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Málaga, Spain.
Florian van BömmelSection of Hepatology, Clinic of Gastroenterology and Hepatology, University Hospital Leipzig, Leipzig, Germany.
Thierry PoynardDepartment of Hepatology, Groupe Hospitalier Pitié Salpêtrière, University Pierre et Marie Curie, INSERM UMR 938, Paris, France.
Paul B WatkinsInstitute for Drug Safety Sciences, University of North Carolina at Chapel Hill, Research Triangle Park, NC.
University of North Carolina at Chapel Hill · USDeerfield (United States) · USResearch Triangle Park Foundation · USNatural and Medical Sciences Institute · DEPfizer (United States) · USUniversity of Zurich · CHIndiana University – Purdue University Indianapolis · USKarolinska Institutet · SENovartis Institutes for BioMedical ResearchPredictive Science (United States) · USUniversity Hospital Leipzig · DEUniversity of Michigan–Ann Arbor · USWake Forest University · US

Funding

Michigan Institute for Clinical and Health Research (MICHR)UL1TR002240 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUMENG, JULIE C, MASHOUR, GEORGE ALEXANDER · 2017 to 2022
$54.9M
MICHIGAN INSTITUTE FOR CLINICAL AND HEALTH RESEARCH (MICHR) (UL1): (BPCA)UL1RR024986 · NCRR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHANLEY, THOMAS P. · 2007 to 2011
$51.2M
UNC CLINICAL AND TRANSLATIONAL SCIENCE AWARD: BPCAUL1RR025747 · NCRR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RUNGE, MARSCHALL S. · 2008 to 2011
$44.6M
UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Melissa A. Troester · 2001 to 2026
$36.3M
Wake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3M
Drug Induced Liver Injury Network Data Coordinating CenterU01DK065176 · NIDDK · DUKE UNIVERSITY · PI Huiman X Barnhart · 2003 to 2026
$25.5M
INDIANA CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE (UL1): BPCAUL1RR025761 · NCRR · INDIANA UNIVERSITY INDIANAPOLIS · PI SHEKHAR, ANANTHA · 2008 to 2011
$21.0M
IU Clinical Center: Drug Induced Liver Injury NetworkU01DK065211 · NIDDK · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI NAGA P CHALASANI · 2003 to 2026
$7.5M
University of North Carolina Clinical Center for DILINU01DK065201 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PAUL B WATKINS · 2003 to 2026
$7.3M
Michigan Hepatotoxicity Clinical Research Network Renewal 2018U01DK065184 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ROBERT J FONTANA · 2003 to 2026
$7.0M
The Drug Induced Liver Injury Network (DILIN): Focus on Herbal and DietarySupplementsU01DK083027 · NIDDK · THOMAS JEFFERSON UNIVERSITY · PI Dina Halegoua-DeMarzio · 2008 to 2026
$7.0M
USC-UCLA Drug-Induced Liver Injury (DILI) Clinical Center.U01DK083020 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Lily Dara · 2008 to 2026
$5.9M
European Federation of Pharmaceutical Industries and Associations companiesEuropean Union's Seventh Framework Programme FP7/2007-2013Innovative Medicines Initiative Joint Undertaking 115003National Institute for Health Research Nottingham Digestive Diseases Biomedical Research Unit at the Nottingham University Hospitals National Health Service TrustNCATS NIH HHS TL1 TR001107NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR002240NCRR NIH HHS UL1 RR024986NCRR NIH HHS UL1 RR025747NCRR NIH HHS UL1 RR025761NIDDK NIH HHS U01 DK065176NIDDK NIH HHS U01 DK065184NIDDK NIH HHS U01 DK065193NIDDK NIH HHS U01 DK065201NIDDK NIH HHS U01 DK065211NIDDK NIH HHS U01 DK065238NIDDK NIH HHS U01 DK082992NIDDK NIH HHS U01 DK083020NIDDK NIH HHS U01 DK083023NIDDK NIH HHS U01 DK083027NIDDK NIH HHS U01-DK083027NIDDK NIH HHS U01 DK100928NIEHS NIH HHS P30 ES010126University of Nottingham
6 · The paper itself

Abstract

Current blood biomarkers are suboptimal in detecting drug-induced liver injury (DILI) and predicting its outcome. We sought to characterize the natural variabilty and performance characteristics of 14 promising DILI biomarker candidates. Serum or plasma from multiple cohorts of healthy volunteers (n = 192 and n = 81), subjects who safely took potentially hepatotoxic drugs without adverse effects (n = 55 and n = 92) and DILI patients (n = 98, n = 28, and n = 143) were assayed for microRNA-122 (miR-122), glutamate dehydrogenase (GLDH), total cytokeratin 18 (K18), caspase cleaved K18, glutathione S-transferase α, alpha-fetoprotein, arginase-1, osteopontin (OPN), sorbitol dehydrogenase, fatty acid binding protein, cadherin-5, macrophage colony-stimulating factor receptor (MCSFR), paraoxonase 1 (normalized to prothrombin protein), and leukocyte cell-derived chemotaxin-2. Most candidate biomarkers were significantly altered in DILI cases compared with healthy volunteers. GLDH correlated more closely with gold standard alanine aminotransferase than miR-122, and there was a surprisingly wide inter- and intra-individual variability of miR-122 levels among healthy volunteers. Serum K18, OPN, and MCSFR levels were most strongly associated with liver-related death or transplantation within 6 months of DILI onset. Prediction of prognosis among DILI patients using the Model for End-Stage Liver Disease was improved by incorporation of K18 and MCSFR levels. Conclusion: GLDH appears to be more useful than miR-122 in identifying DILI patients, and K18, OPN, and MCSFR are promising candidates for prediction of prognosis during an acute DILI event. Serial assessment of these biomarkers in large prospective studies will help further delineate their role in DILI diagnosis and management.

Indexed as

AdultBiomarkersCase-Control StudiesChemical and Drug Induced Liver InjuryFemaleHumansMaleMiddle AgedPrognosisBiomarkers

Identifiers

PMID29357190
PMCPMC6054900
OpenAlexW2789357631

What OpenQuestion holds

Textmetadata
LicenceTDM
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.