Evidence map›Paper›PMID 25568858›Full record

ReviewHepatobiliary surgery and nutrition2014

Immune mechanisms in acetaminophen-induced acute liver failure.

Oliver Krenkel, Jana C Mossanen, Frank Tacke

3 registry-linked trialsAbstract readReview
In one paragraph

Review in Hepatobiliary surgery and nutrition, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 123 papers.

0numbers the graph read from it
0cells of the map it votes in
123citing papers in PubMed
18.8field-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.

NCT02593721 phase2 / phase3completednot on this mapstarted 2015, after this paper: background citation

Hypoalgesic Effect of Median Nerve Neural Mobilization Versus Ibuprofen Pharmacologic Treatment in Patients With Cervicobrachial Pain

TypeinterventionalSponsorUniversidad Europea de MadridRan2015 to 2015Enrolled50ConditionsCervicobrachial NeuralgiaArmsMedian Nerve Neural Mobilization, Ibuprofen
NCT02595294 nacompletednot on this mapstarted 2015, after this paper: background citation

Hypoalgesic Effect of Neural Mobilization in Cervicobrachial Pain Compared to a Controlled Group

TypeinterventionalSponsorUniversidad Europea de MadridRan2015 to 2015Enrolled52ConditionsCervicobrachial NeuralgiaArmsCervical Lateral Glide neural mobilization
NCT02596815 nacompletednot on this mapstarted 2015, after this paper: background citation

Hypoalgesic Effect of Median Nerve Neural Mobilization in Cervicobrachial Pain Compared to a Controlled Group

TypeinterventionalSponsorUniversidad Europea de MadridRan2015 to 2015Enrolled51ConditionsCervicobrachial NeuralgiaArmsMedian Nerve Neural Mobilization, Goniometer
3 · Its place in the literature

Who cites it

123 citing papers in PubMed, 219 citations in OpenAlex.

  1. Trial
  2. Mesenchymal Stromal Cell-Based Cell-Drug Conjugates for the Treatment of Acute Liver Failure.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Article
  4. Article
  5. Review
  6. Pharmacological inhibition of G protein-coupled receptor kinase 2 (GRK2) by paroxetine attenuates acetaminophen-induced hepatotoxicity.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Discovery of intrahepatic CD103Experimental & molecular medicine · 2025
    Article
  13. Iron overload in CD11cCommunications biology · 2025
    Article
  14. Article
  15. Protective Effects of Methanolic Extract ofInternational journal of molecular sciences · 2025
    Article
  16. Article
  17. Article
  18. Article
  19. In vitro liver models for toxicological research.Drug metabolism and pharmacokinetics · 2025
    Review
  20. Article

63 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

3 authors at 2 institutions in 1 country.

Oliver KrenkelDepartment of Medicine III, RWTH-University Hospital Aachen, Aachen, Germany.
Jana C MossanenDepartment of Medicine III, RWTH-University Hospital Aachen, Aachen, Germany.
Frank TackeDepartment of Medicine III, RWTH-University Hospital Aachen, Aachen, Germany.
Universitätsklinikum Aachen · DERWTH Aachen University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

An overdose of acetaminophen (N-acetyl-p-aminophenol, APAP), also termed paracetamol, can cause severe liver damage, ultimately leading to acute liver failure (ALF) with the need of liver transplantation. APAP is rapidly taken up from the intestine and metabolized in hepatocytes. A small fraction of the metabolized APAP forms cytotoxic mitochondrial protein adducts, leading to hepatocyte necrosis. The course of disease is not only critically influenced by dose of APAP and the initial hepatocyte damage, but also by the inflammatory response following acetaminophen-induced liver injury (AILI). As revealed by mouse models of AILI and corresponding translational studies in ALF patients, necrotic hepatocytes release danger-associated-molecular patterns (DAMPs), which are recognized by resident hepatic macrophages, Kupffer cell (KC), and neutrophils, leading to the activation of these cells. Activated hepatic macrophages release various proinflammatory cytokines, such as TNF-α or IL-1β, as well as chemokines (e.g., CCL2) thereby further enhancing inflammation and increasing the influx of immune cells, like bone-marrow derived monocytes and neutrophils. Monocytes are mainly recruited via their receptor CCR2 and aggravate inflammation. Infiltrating monocytes, however, can mature into monocyte-derived macrophages (MoMF), which are, in cooperation with neutrophils, also involved in the resolution of inflammation. Besides macrophages and neutrophils, distinct lymphocyte populations, especially γδ T cells, are also linked to the inflammatory response following an APAP overdose. Natural killer (NK), natural killer T (NKT) and T cells possibly further perpetuate inflammation in AILI. Understanding the complex interplay of immune cell subsets in experimental models and defining their functional involvement in disease progression is essential to identify novel therapeutic targets for human disease.

Indexed as

Acetaminophen (APAP)acute liver failure (ALF)immune responseliver injurymacrophages

Identifiers

PMID25568858
PMCPMC4273118
OpenAlexW1959937474

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.