Evidence mapPaperPMID 36927865Full record

SynthesisNature communications2023

Clinically important alterations in pharmacogene expression in histologically severe nonalcoholic fatty liver disease.

Nicholas R Powell, Tiebing Liang, Joseph Ipe, Sha Cao, Todd C Skaar, Zeruesenay Desta, Hui-Rong Qian, Philip J Ebert, Yu Chen, Melissa K Thomas and 1 more

Open access · goldFull text readMeta-Analysis
In one paragraph

Synthesis in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
7.9field-weighted citation impact, top 2% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Impact of PNPLA3 I148M on Drug-Induced Hepatocellular Liver Injury: A Systematic Review and Meta-Analysis.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Pooled it
  2. Integrative Multi-Omics Analysis Elucidates the Progressive Disease Landscape and Reveals Dynamic Protein Biomarkers for MASLD Surveillance.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  3. Genomic Impacts of Biological Exposures.Journal of developmental biology · 2026
    Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Effect ofPharmaceuticals (Basel, Switzerland) · 2025
    Article
  9. Article
  10. Drug-Induced Liver Injury in Patients With Chronic Liver Disease.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Review
  11. Liver-specific actions of GH and IGF1 that protect against MASLD.Nature reviews. Endocrinology · 2025 · on this map
    Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
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

11 authors at 2 institutions in 1 country.

Nicholas R PowellIndiana University School of Medicine, Department of Medicine, Division of Clinical Pharmacology, Indianapolis, IN, USA.ORCID 0000-0003-4572-0733
Tiebing LiangIndiana University School of Medicine, Department of Medicine, Division of Gastroenterology Hepatology, Indianapolis, IN, USA.ORCID 0000-0002-8445-3765
Joseph IpeIndiana University School of Medicine, Department of Medicine, Division of Clinical Pharmacology, Indianapolis, IN, USA.
Sha CaoIndiana University School of Medicine, Department of Medicine, Division of Gastroenterology Hepatology, Indianapolis, IN, USA.ORCID 0000-0002-8645-848X
Todd C SkaarIndiana University School of Medicine, Department of Medicine, Division of Clinical Pharmacology, Indianapolis, IN, USA.
Zeruesenay DestaIndiana University School of Medicine, Department of Medicine, Division of Clinical Pharmacology, Indianapolis, IN, USA.
Hui-Rong QianEli Lilly and Company, Indianapolis, IN, USA.
Philip J EbertEli Lilly and Company, Indianapolis, IN, USA.
Yu ChenEli Lilly and Company, Indianapolis, IN, USA.
Melissa K ThomasEli Lilly and Company, Indianapolis, IN, USA.
Naga ChalasaniIndiana University School of Medicine, Department of Medicine, Division of Gastroenterology Hepatology, Indianapolis, IN, USA. nchalasa@iu.edu.ORCID 0000-0003-4082-3178
Indiana University School of MedicineEli Lilly (United States) · US

Funding

Indiana University Comprehensive Training in Clinical PharmacologyT32GM008425 · NIGMS · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · 1992 to 2025
$2.0M
Genomic and drug-drug interaction mechanisms of interindividual variability in drug dispositionR35GM145383 · INDIANA UNIVERSITY INDIANAPOLIS · 2025 to 2025
$396k
NIGMS NIH HHS R35 GM131812NIGMS NIH HHS R35 GM145383NIGMS NIH HHS T32 GM008425
6 · The paper itself

Abstract

Polypharmacy is common in patients with nonalcoholic fatty liver disease (NAFLD) and previous reports suggest that NAFLD is associated with altered drug disposition. This study aims to determine if patients with NAFLD are at risk for altered drug response by characterizing changes in hepatic mRNA expression of genes mediating drug disposition (pharmacogenes) across the histological NAFLD severity spectrum. We utilize RNA-seq for 93 liver biopsies with histologically staged NAFLD Activity Score (NAS), fibrosis stage, and steatohepatitis (NASH). We identify 37 significant pharmacogene-NAFLD severity associations including CYP2C19 downregulation. We chose to validate CYP2C19 due to its actionability in drug prescribing. Meta-analysis of 16 independent studies demonstrate that CYP2C19 is significantly downregulated to 46% in NASH, to 58% in high NAS, and to 43% in severe fibrosis. Our data demonstrate the downregulation of CYP2C19 in NAFLD which supports developing personalized medicine approaches for drugs sensitive to metabolism by the CYP2C19 enzyme.

Indexed as

Non-alcoholic Fatty Liver DiseaseBiopsyCytochrome P-450 CYP2C19HumansLiverLiver CirrhosisCytochrome P-450 CYP2C19

Identifiers

PMID36927865
PMCPMC10020163
OpenAlexW4327675663

What Socratic holds

Textfull text, public
LicenceCC BY
measurements read39
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.