Evidence map›Paper›PMID 36738840›Full record

ArticleJournal of hepatology2023

A human liver organoid screening platform for DILI risk prediction.

Charles J Zhang, Sophia R Meyer, Matthew J O'Meara, Sha Huang, Meghan M Capeling, Daysha Ferrer-Torres, Charlie J Childs, Jason R Spence, Robert J Fontana, Jonathan Z Sexton

Open access · hybridAbstract read
In one paragraph

Article in Journal of hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed
32.6field-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

96 citing papers in PubMed, 152 citations in OpenAlex.

  1. Review
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  5. Review of in vitro approaches for assessing the toxicity of chemical stressors across diverse physiological systems.Toxicological sciences : an official journal of the Society of Toxicology · 2026
    Review
  6. Review
  7. Article
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  9. Review
  10. Article
  11. New developments and applications of human organoids.Nature reviews. Molecular cell biology · 2026
    Review
  12. Review
  13. Article
  14. Organ-on-a-chip toxicology.Innovation (Cambridge (Mass.)) · 2026
    Review
  15. Review
  16. Article
  17. Review
  18. Review
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36 more citing papers are in PubMed but not listed here.

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

10 authors at 2 institutions in 1 country.

Charles J ZhangDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA.
Sophia R MeyerDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA.
Matthew J O'MearaDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.
Sha HuangDepartment of Internal Medicine, Gastroenterology and Hepatology, Michigan Medicine at the University of Michigan, Ann Arbor, MI, 48109, USA.
Meghan M CapelingDepartment of Internal Medicine, Gastroenterology and Hepatology, Michigan Medicine at the University of Michigan, Ann Arbor, MI, 48109, USA.
Daysha Ferrer-TorresDepartment of Internal Medicine, Gastroenterology and Hepatology, Michigan Medicine at the University of Michigan, Ann Arbor, MI, 48109, USA.
Charlie J ChildsDepartment of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
Jason R SpenceDepartment of Internal Medicine, Gastroenterology and Hepatology, Michigan Medicine at the University of Michigan, Ann Arbor, MI, 48109, USA; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
Robert J FontanaDepartment of Internal Medicine, Gastroenterology and Hepatology, Michigan Medicine at the University of Michigan, Ann Arbor, MI, 48109, USA.
Jonathan Z SextonDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Internal Medicine, Gastroenterology and Hepatology, Michigan Medicine at the University of Michigan, Ann Arbor, MI, 48109, USA; U-M Center for Drug Repurposing, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address: jzsexton@med.umich.edu.
University of Michigan · USMichigan Medicine · 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
University of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OMARY, BISHR · 1986 to 2021
$22.5M
Michigan Hepatotoxicity Clinical Research Network Renewal 2018U01DK065184 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ROBERT J FONTANA · 2003 to 2026
$7.0M
Small molecules for expansion of islet beta-cell mass in diabetesR01DK120623 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NEWGARD, CHRISTOPHER B, SEXTON, JONATHAN ZACHARY · 2019 to 2021
$2.0M
Laser-based high content imaging microscopeS10OD034245 · OD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SEXTON, JONATHAN ZACHARY · 2024 to 2024
$1.4M
NCATS NIH HHS UL1 TR002240NIDDK NIH HHS P30 DK034933NIDDK NIH HHS R01 DK120623NIDDK NIH HHS U01 DK065184NIH HHS S10 OD034245
6 · The paper itself

Abstract

BACKGROUND &

aimsDrug-induced liver injury (DILI), both intrinsic and idiosyncratic, causes frequent morbidity, mortality, clinical trial failures and post-approval withdrawal. This suggests an unmet need for improved in vitro models for DILI risk prediction that can account for diverse host genetics and other clinical factors. In this study, we evaluated the utility of human liver organoids (HLOs) for high-throughput DILI risk prediction and in an organ-on-chip system.

methodsHLOs were derived from three separate iPSC lines and benchmarked on two platforms for their ability to model in vitro liver function and identify hepatotoxic compounds using biochemical assays for albumin, ALT, AST, microscopy-based morphological profiling, and single-cell transcriptomics: i) HLOs dispersed in 384-well-formatted plates and exposed to a library of compounds; ii) HLOs adapted to a liver-on-chip system.

resultsDispersed HLOs derived from the three iPSC lines had similar DILI predictive capacity as intact HLOs in a high-throughput screening format, allowing for measurable IC

conclusionsThe high-throughput and liver-on-chip systems exhibit enhanced in vivo-like functions and demonstrate the potential utility of these platforms for DILI risk assessment. Tenofovir-inarigivr-associated hepatotoxicity was observed and correlates with the clinical manifestation of DILI observed in patients. IMPACT AND IMPLICATIONS: Idiosyncratic (spontaneous, patient-specific) drug-induced liver injury (DILI) is difficult to study due to the lack of liver models that function as human liver tissue and are adaptable for large-scale drug screening. Human liver organoids grown from patient stem cells respond to known DILI-causing drugs in both a high-throughput and on a physiological "chip" culture system. These platforms show promise for researchers in their use as predictive models for novel drugs before entering clinical trials and as a potential in vitro diagnostic tool. Our findings support further development of patient-derived liver organoid lines and their use in the context of DILI research.

Indexed as

Chemical and Drug Induced Liver InjuryDrug-Related Side Effects and Adverse ReactionsAlbuminsHepatocytesHumansLiverOrganoidsAlbuminsdrug developmenthepatotoxicityhigh-content imagingmicrofluidic devices

Identifiers

PMID36738840
PMCPMC11268729
OpenAlexW4319160895

What OpenQuestion holds

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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.