Evidence map›Paper›PMID 27634375›Full record

ArticleScientific reports2016

FXR agonist obeticholic acid reduces hepatic inflammation and fibrosis in a rat model of toxic cirrhosis.

Len Verbeke, Inge Mannaerts, Robert Schierwagen, Olivier Govaere, Sabine Klein, Ingrid Vander Elst, Petra Windmolders, Ricard Farre, Mathias Wenes, Massimiliano Mazzone and 4 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.

0numbers the graph read from it
0cells of the map it votes in
119citing papers in PubMed
16.7field-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

119 citing papers in PubMed, 227 citations in OpenAlex.

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  15. Interaction of inflammation and portal hypertension in cirrhosis progression.Nature reviews. Gastroenterology & hepatology · 2025
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59 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

14 authors at 4 institutions in 3 countries.

Len VerbekeDivision of Liver and Biliopancreatic disorders, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium.
Inge MannaertsLiver Cell Biology Laboratory, Vrije Universiteit Brussel, Brussels, Belgium.
Robert SchierwagenDepartment of Internal Medicine I, University of Bonn, Bonn, Germany.
Olivier GovaereTranslational Cell and Tissue Research, Department of Imaging and Pathology, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium.
Sabine KleinDepartment of Internal Medicine I, University of Bonn, Bonn, Germany.
Ingrid Vander ElstDivision of Liver and Biliopancreatic disorders, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium.
Petra WindmoldersDivision of Liver and Biliopancreatic disorders, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium.
Ricard FarreTranslational Research Center for Gastrointestinal Disorders, KU Leuven - University of Leuven, Leuven, Belgium.
Mathias WenesLaboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, Department of Oncology, KU Leuven - University of Leuven, Belgium.
Massimiliano MazzoneLaboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, Department of Oncology, KU Leuven - University of Leuven, Belgium.
Frederik NevensDivision of Liver and Biliopancreatic disorders, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium.
Leo A van GrunsvenLiver Cell Biology Laboratory, Vrije Universiteit Brussel, Brussels, Belgium.
Jonel TrebickaDepartment of Internal Medicine I, University of Bonn, Bonn, Germany.
Wim LalemanDivision of Liver and Biliopancreatic disorders, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium.
KU Leuven · BEUniversity of Bonn · DEVrije Universiteit Brussel · BECentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepatic inflammation drives hepatic stellate cells (HSC), resulting in liver fibrosis. The Farnesoid-X receptor (FXR) antagonizes inflammation through NF-κB inhibition. We investigated preventive and therapeutic effects of FXR agonist obeticholic acid (OCA) on hepatic inflammation and fibrosis in toxic cirrhotic rats. Cirrhosis was induced by thioacetamide (TAA) intoxication. OCA was given during or after intoxication with vehicle-treated rats as controls. At sacrifice, fibrosis, hemodynamic and biochemical parameters were assessed. HSC activation, cell turn-over, hepatic NF-κB activation, pro-inflammatory and pro-fibrotic cytokines were determined. The effect of OCA was further evaluated in isolated HSC, Kupffer cells, hepatocytes and liver sinusoidal endothelial cells (LSEC). OCA decreased hepatic inflammation and fibrogenesis during TAA-administration and reversed fibrosis in established cirrhosis. Portal pressure decreased through reduced intrahepatic vascular resistance. This was paralleled by decreased expression of pro-fibrotic cytokines (transforming growth-factor β, connective tissue growth factor, platelet-derived growth factor β-receptor) as well as markers of hepatic cell turn-over, by blunting effects of pro-inflammatory cytokines (e.g. monocyte chemo-attractant protein-1). In vitro, OCA inhibited both LSEC and Kupffer cell activation; while HSC remained unaffected. This related to NF-κB inhibition via up-regulated IκBα. In conclusion, OCA inhibits hepatic inflammation in toxic cirrhotic rats resulting in decreased HSC activation and fibrosis.

Indexed as

AnimalsApoptosisBiomarkersCell CycleCell LineCell ProliferationChenodeoxycholic AcidCytokinesDisease Models, AnimalEndothelial CellsHemodynamicsHepatic Stellate CellsHepatocytesHumansInflammationInflammation MediatorsBiomarkersChenodeoxycholic AcidCytokinesInflammation MediatorsLipopolysaccharidesNF-kappa BNF-KappaB Inhibitor alphaobeticholic acidReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearThioacetamideTumor Necrosis Factor-alpha

Identifiers

PMID27634375
PMCPMC5025787
OpenAlexW2519114186

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Registered trials

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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.