ArticleGut2015
Progenitor cell expansion and impaired hepatocyte regeneration in explanted livers from alcoholic hepatitis.
Article in Gut, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
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Who cites it
91 citing papers in PubMed, 2 syntheses or guidelines pooled it, 174 citations in OpenAlex.
- Role of granulocyte colony stimulating factor in the treatment of cirrhosis of liver: a systematic review.The Journal of international medical research · 2023Pooled it
- ACG Clinical Guideline: Alcoholic Liver Disease.The American journal of gastroenterology · 2018Guideline
- Article
- Hepatoprotective effects of resolvin D1 in mice exposed to ethanol and galactosamine.Hepatology communications · 2026Article
- Chronic Cholestatic Liver Disease Induced by Larval Ascariasis: Novel Insights Into Immune-Mediated Pathogenesis and Hepatic Fibrosis in Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Acute-on-chronic liver failure: pathophysiological mechanisms and clinical management.Nature reviews. Gastroenterology & hepatology · 2026Review
- Preoperative Beta-Hydroxy-Beta-Methyl-Butyrate Supplementation Reduces Mitochondrial Dynamics Proteins and Preserves Hepatic Mitochondrial Function After Partial Hepatectomy in Mice.Acta physiologica (Oxford, England) · 2026Article
- Deficiency of ZFP36L1 and ZFP36L2 impairs liver homeostasis and initiates cholestatic liver injury.Hepatology communications · 2026Article
- Oxidative Stress and Alcohol-Related Hepatitis: A Role for Future Therapies.Antioxidants (Basel, Switzerland) · 2026Review
- Bilirubin-Driven Phenotype Identifies Higher Mortality Risk in Severe Alcohol-Associated Hepatitis.Gastro hep advances · 2026Article
- Cholestasis in Alcohol-Associated Liver Disease.The American journal of pathology · 2026Review
- Protective anti-fibrotic effect of liraglutide and Pirfenidone combination therapy on liver fibrosis in rats: effects on autophagy and NLRP3 inflammasome.BMC gastroenterology · 2025Article
- Derepression of the epithelial transcription factor GRHL2 promotes direct hepatocyte-to-cholangiocyte transdifferentiation.PLoS biology · 2025Article
- Alcohol-related hepatitis induces a specific fibrosis profile through YAP activation in myofibroblasts.JHEP reports : innovation in hepatology · 2025Article
- Short-chain per- and polyfluoroalkyl substances associate with elevated alanine aminotransferase: Cross-sectional analysis results from the STRIVE cohort.Environmental research · 2025Article
- Liver Progenitor Cells: Cellular Origins, Plasticity, and Signaling Pathways in Liver Regeneration.Biology · 2025Review
- Dysregulated RNA splicing impairs regeneration in alcohol-associated liver disease.Nature communications · 2025Article
- Analysis of the factors influencing liver regeneration after hepatectomy in hepatocellular carcinoma patients and the relationship between liver regeneration and prognosis.Scientific reports · 2025Article
- In vitro liver models for toxicological research.Drug metabolism and pharmacokinetics · 2025Review
- Microenvironmental control of the ductular reaction: balancing repair and disease progression.Cell death & disease · 2025Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
objectiveIn alcoholic hepatitis (AH), development of targeted therapies is crucial and requires improved knowledge of cellular and molecular drivers in liver dysfunction. The unique opportunity of using explanted livers from patients with AH having undergone salvage liver transplantation allowed to perform more in-depth molecular translational studies.
designWe studied liver explants from patients with AH submitted to salvage transplantation (n=16), from patients with alcoholic cirrhosis without AH (n=12) and fragments of normal livers (n=16). Hepatic cytokine content was quantified. Hepatocyte function and proliferation and the presence of hepatic progenitor cells (HPCs) were evaluated by immunohistochemistry, western blot or quantitative PCR. Mitochondrial morphology was evaluated by electron microscopy.
resultsLivers from patients with AH showed decreased cytokine levels involved in liver regeneration (tumour necrosis factor α and interleukin-6), as well as a virtual absence of markers of hepatocyte proliferation compared with alcoholic cirrhosis and normal livers. Electron microscopy revealed obvious mitochondrial abnormalities in AH hepatocytes. Importantly, livers from patients with AH showed substantial accumulation of HPCs that, unexpectedly, differentiate only into biliary cells. AH livers predominantly express laminin (extracellular matrix protein favouring cholangiocyte differentiation); consequently, HPC expansion is inefficient at yielding mature hepatocytes.
conclusionsAH not responding to medical therapy is associated with lack of expression of cytokines involved in liver regeneration and profound mitochondrial damage along with lack of proliferative hepatocytes. Expansion of HPCs is inefficient to yield mature hepatocytes. Manoeuvres aimed at promoting differentiation of HPCs into mature hepatocytes should be tested in AH.
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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.