Evidence map›Paper›PMID 34322741›Full record

ReviewArchives of toxicology2021

The application of cytokeratin-18 as a biomarker for drug-induced liver injury.

Samantha Korver, Joanne Bowen, Kara Pearson, Raymond J Gonzalez, Neil French, Kevin Park, Rosalind Jenkins, Christopher Goldring

Open access · hybridAbstract readReview
In one paragraph

Review in Archives of toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
5.0field-weighted citation impact, top 4% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
  2. 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
  3. Article
  4. Review
  5. Circulating Liver-Derived and CD36Journal of extracellular vesicles · 2026
    Article
  6. Review
  7. Review
  8. Review
  9. Subclinical Hepatic Injury and Dysfunction Following Surgery: Evidence From a Young and Aged Laparotomy Murine Model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Vincamine Mitigates Methotrexate-Induced Liver Fibrosis Model.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2025
    Article
  15. In vitro liver models for toxicological research.Drug metabolism and pharmacokinetics · 2025
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
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

8 authors at 3 institutions in 3 countries.

Samantha KorverDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK. S.Korver@liverpool.ac.uk.ORCID 0000-0001-7670-3093
Joanne BowenAdelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia.
Kara PearsonMerck and Co. Inc, Kenilworth, NJ, USA.
Raymond J GonzalezMerck and Co. Inc, Kenilworth, NJ, USA.
Neil FrenchDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
Kevin ParkDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
Rosalind JenkinsDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
Christopher GoldringDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
University of Liverpool · GBMerck & Co., Inc., Rahway, NJ, USA (United States) · USThe University of Adelaide · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Drug-induced liver injury (DILI) is a frequent and dangerous adverse effect faced during preclinical and clinical drug therapy. DILI is a leading cause of candidate drug attrition, withdrawal and in clinic, is the primary cause of acute liver failure. Traditional diagnostic markers for DILI include alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Yet, these routinely used diagnostic markers have several noteworthy limitations, restricting their sensitivity, specificity and accuracy in diagnosing DILI. Consequently, new biomarkers for DILI need to be identified.A potential biomarker for DILI is cytokeratin-18 (CK18), an intermediate filament protein highly abundant in hepatocytes and cholangiocytes. Extensively researched in a variety of clinical settings, both full length and cleaved forms of CK18 can diagnose early-stage DILI and provide insight into the mechanism of hepatocellular injury compared to traditionally used diagnostic markers. However, relatively little research has been conducted on CK18 in preclinical models of DILI. In particular, CK18 and its relationship with DILI is yet to be characterised in an in vivo rat model. Such characterization of CK18 and ccCK18 responses may enable their use as translational biomarkers for hepatotoxicity and facilitate management of clinical DILI risk in drug development. The aim of this review is to discuss the application of CK18 as a biomarker for DILI. Specifically, this review will highlight the properties of CK18, summarise clinical research that utilised CK18 to diagnose DILI and examine the current challenges preventing the characterisation of CK18 in an in vivo rat model of DILI.

Indexed as

BiomarkersChemical and Drug Induced Liver InjuryHumansKeratin-18LiverBiomarkersKeratin-18BiomarkerCytokeratin-18 (CK18)Drug-induced liver injury (DILI)HepatotoxicityIn vivo

Identifiers

PMID34322741
PMCPMC8492595
OpenAlexW3183984279

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.