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Utility of spherical human liver microtissues for prediction of clinical drug-induced liver injury

Overview of attention for article published in Archives of Toxicology, June 2017
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#32 of 2,827)
  • High Attention Score compared to outputs of the same age (95th percentile)
  • High Attention Score compared to outputs of the same age and source (92nd percentile)

Citations

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265 Mendeley
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Title
Utility of spherical human liver microtissues for prediction of clinical drug-induced liver injury
Published in
Archives of Toxicology, June 2017
DOI 10.1007/s00204-017-2002-1
Pubmed ID
Authors

William R. Proctor, Alison J. Foster, Jennifer Vogt, Claire Summers, Brian Middleton, Mark A. Pilling, Daniel Shienson, Monika Kijanska, Simon Ströbel, Jens M. Kelm, Paul Morgan, Simon Messner, Dominic Williams

Abstract

Drug-induced liver injury (DILI) continues to be a major source of clinical attrition, precautionary warnings, and post-market withdrawal of drugs. Accordingly, there is a need for more predictive tools to assess hepatotoxicity risk in drug discovery. Three-dimensional (3D) spheroid hepatic cultures have emerged as promising tools to assess mechanisms of hepatotoxicity, as they demonstrate enhanced liver phenotype, metabolic activity, and stability in culture not attainable with conventional two-dimensional hepatic models. Increased sensitivity of these models to drug-induced cytotoxicity has been demonstrated with relatively small panels of hepatotoxicants. However, a comprehensive evaluation of these models is lacking. Here, the predictive value of 3D human liver microtissues (hLiMT) to identify known hepatotoxicants using a panel of 110 drugs with and without clinical DILI has been assessed in comparison to plated two-dimensional primary human hepatocytes (PHH). Compounds were treated long-term (14 days) in hLiMT and acutely (2 days) in PHH to assess drug-induced cytotoxicity over an 8-point concentration range to generate IC50 values. Regardless of comparing IC50 values or exposure-corrected margin of safety values, hLiMT demonstrated increased sensitivity in identifying known hepatotoxicants than PHH, while specificity was consistent across both assays. In addition, hLiMT out performed PHH in correctly classifying hepatotoxicants from different pharmacological classes of molecules. The hLiMT demonstrated sufficient capability to warrant exploratory liver injury biomarker investigation (miR-122, HMGB1, α-GST) in the cell-culture media. Taken together, this study represents the most comprehensive evaluation of 3D spheroid hepatic cultures up to now and supports their utility for hepatotoxicity risk assessment in drug discovery.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 265 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 265 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 57 22%
Student > Ph. D. Student 42 16%
Student > Bachelor 28 11%
Student > Master 26 10%
Other 18 7%
Other 32 12%
Unknown 62 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 44 17%
Pharmacology, Toxicology and Pharmaceutical Science 43 16%
Agricultural and Biological Sciences 34 13%
Engineering 16 6%
Medicine and Dentistry 12 5%
Other 36 14%
Unknown 80 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 54. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 February 2023.
All research outputs
#760,961
of 25,084,886 outputs
Outputs from Archives of Toxicology
#32
of 2,827 outputs
Outputs of similar age
#15,996
of 323,264 outputs
Outputs of similar age from Archives of Toxicology
#3
of 27 outputs
Altmetric has tracked 25,084,886 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,827 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.6. This one has done particularly well, scoring higher than 98% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 323,264 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 95% of its contemporaries.
We're also able to compare this research output to 27 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 92% of its contemporaries.