↓ Skip to main content

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
Altmetric Badge

About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#18 of 1,915)
  • High Attention Score compared to outputs of the same age (94th percentile)
  • High Attention Score compared to outputs of the same age and source (93rd percentile)

Citations

dimensions_citation
56 Dimensions

Readers on

mendeley
125 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
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.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 125 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 125 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 32 26%
Student > Ph. D. Student 26 21%
Student > Master 17 14%
Unspecified 11 9%
Other 11 9%
Other 28 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 27 22%
Agricultural and Biological Sciences 26 21%
Pharmacology, Toxicology and Pharmaceutical Science 26 21%
Unspecified 19 15%
Medicine and Dentistry 7 6%
Other 20 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 50. 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 31 October 2018.
All research outputs
#354,537
of 13,722,218 outputs
Outputs from Archives of Toxicology
#18
of 1,915 outputs
Outputs of similar age
#11,379
of 224,485 outputs
Outputs of similar age from Archives of Toxicology
#1
of 15 outputs
Altmetric has tracked 13,722,218 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,915 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.3. This one has done particularly well, scoring higher than 99% 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 224,485 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 94% of its contemporaries.
We're also able to compare this research output to 15 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 93% of its contemporaries.