Evidence map›Paper›PMID 33987435›Full record

ReviewAnnals of translational medicine2021

The role of bile acids in cholestatic liver injury.

Shi-Ying Cai, James L Boyer

Open access · diamondAbstract readReview
In one paragraph

Review in Annals of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 3% 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

56 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.

  1. Dysregulation of serum bile acids in liver cancer: a systematic review and meta-analysis.Metabolomics : Official journal of the Metabolomic Society · 2025
    Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  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

2 authors at 1 institution in 1 country.

Shi-Ying CaiDepartment of Internal Medicine and Liver Center, Yale University School of Medicine, New Haven, CT 06520, USA.
James L BoyerDepartment of Internal Medicine and Liver Center, Yale University School of Medicine, New Haven, CT 06520, USA.
Yale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Liver CenterP30DK034989 · NIDDK · YALE UNIVERSITY · PI WAJAHAT Zafar MEHAL · 1986 to 2026
$31.1M
MECHANISMS OF BILE SECRETION &CHOLESTASISR37DK025636 · NIDDK · YALE UNIVERSITY · PI BOYER, JAMES LORENZEN · 1990 to 2017
$9.7M
MECHANISMS OF BILE SECRETION AND CHOLESTASISR01DK025636 · NIDDK · YALE UNIVERSITY · PI BOYER, JAMES LORENZEN · 1986 to 2007
$6.1M
NCATS NIH HHS UL1 TR001863NIDDK NIH HHS P30 DK034989NIDDK NIH HHS R01 DK025636NIDDK NIH HHS R37 DK025636
6 · The paper itself

Abstract

Clinical disorders that impair bile flow result in retention of bile acids and cholestatic liver injury, characterized by parenchymal cell death, bile duct proliferation, liver inflammation and fibrosis. However, the pathogenic role of bile acids in the development of cholestatic liver injury remains incompletely understood. In this review, we summarize the current understanding of this process focusing on the experimental and clinical evidence for direct effects of bile acids on each major cellular component of the liver: hepatocytes, cholangiocytes, stellate cells and immune cells. During cholestasis bile acids accumulated in the liver, causing oxidative stress and mitochondrial injury in hepatocytes. The stressed hepatocytes respond by releasing inflammatory cytokines through activation of specific signaling pathways and transcription factors. The recruited neutrophils and other immune cells then cause parenchymal cell death. In addition, bile acids also stimulate the proliferation of cholangiocytes and stellate cells that are responsible for bile duct proliferation and liver fibrosis. This review explores the evidence for bile acid involvement in these phenomena. The role of bile acid receptors, TGR5, FXR and the sphingosine-1-phosphate receptor 2 and the inflammasome are also examined. We hope that better understanding of these pathologic effects will facilitate new strategies for treating cholestatic liver injury.

Indexed as

Bile acidcholestatic liver injuryhepatic cellsinflammation

Identifiers

PMID33987435
PMCPMC8106037
OpenAlexW3100713148

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.