ArticleThe Journal of clinical investigation2022
Distinct histopathological phenotypes of severe alcoholic hepatitis suggest different mechanisms driving liver injury and failure.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 81 citations in OpenAlex.
- Neutrophil extracellular traps (NETs) and NETosis in alcohol-associated diseases: A systematic review.Alcohol, clinical & experimental research · 2025Pooled it
- From mechanisms to anti-fibrotic drugs in hepatic stellate cell research: a global bibliometric analysis with patent and clinical perspectives (2000-2025).Frontiers in pharmacology · 2025Pooled it
- [Alcohol liver disease: immunoregulatory mechanisms and precision therapeutic targets].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- IL15-mediated crosstalk between LSECs and CD8⁺ tissue-resident memory T cells drives alcohol-associated hepatitis.Hepatology communications · 2026Article
- Patient-specific modeling identifies metabolic interventions for reversing glucose use reprogramming in alcohol-associated hepatitis.Communications biology · 2026Article
- Association of metabolic vulnerability index with various chronic liver diseases and mortality: a large prospective cohort study.BMC gastroenterology · 2026Article
- α-Diversity analysis of hepatic transcriptome reveals distinct pathways in alcohol-associated hepatitis.JCI insight · 2026Article
- Unified platform for multiplex immunofluorescence across liver tissues and engineered models.eGastroenterology · 2026Article
- IL-6 trans-Signaling Regulates Neutrophilic Inflammation in Alcohol-Associated Hepatitis.The American journal of pathology · 2026Article
- An Update on IL-22 Therapies in Alcohol-Associated Liver Disease and Beyond.The American journal of pathology · 2026Review
- Lipid Droplet Dynamics in Alcoholic Steatohepatitis.The American journal of pathology · 2026Review
- Infiltrating macrophages replace Kupffer cells and play diverse roles in severe alcohol-associated hepatitis.Cellular & molecular immunology · 2025Article
- Physiological Mechanisms Vulnerable to Alcohol-Induced Alterations: Role in Chronic Comorbidities.Comprehensive Physiology · 2025Review
- Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.Cellular & molecular immunology · 2025Review
- IgM Antibodies Targeting Malondialdehyde Promote Complement-Mediated Liver Injury in Alcohol-Related Liver Disease.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Dysregulated RNA splicing impairs regeneration in alcohol-associated liver disease.Nature communications · 2025Article
- Inflammation in MASLD progression and cancer.JHEP reports : innovation in hepatology · 2025Review
- Article
- Article
- Non-coding RNAs in alcohol-associated liver disease.Liver research (Beijing, China) · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 9 institutions in 3 countries.
Funding
Abstract
Intrahepatic neutrophil infiltration has been implicated in severe alcoholic hepatitis (SAH) pathogenesis; however, the mechanism underlying neutrophil-induced injury in SAH remains obscure. This translational study aims to describe the patterns of intrahepatic neutrophil infiltration and its involvement in SAH pathogenesis. Immunohistochemistry analyses of explanted livers identified two SAH phenotypes despite a similar clinical presentation, one with high intrahepatic neutrophils (Neuhi), but low levels of CD8+ T cells, and vice versa. RNA-Seq analyses demonstrated that neutrophil cytosolic factor 1 (NCF1), a key factor in controlling neutrophilic ROS production, was upregulated and correlated with hepatic inflammation and disease progression. To study specifically the mechanisms related to Neuhi in AH patients and liver injury, we used the mouse model of chronic-plus-binge ethanol feeding and found that myeloid-specific deletion of the Ncf1 gene abolished ethanol-induced hepatic inflammation and steatosis. RNA-Seq analysis and the data from experimental models revealed that neutrophilic NCF1-dependent ROS promoted alcoholic hepatitis (AH) by inhibiting AMP-activated protein kinase (a key regulator of lipid metabolism) and microRNA-223 (a key antiinflammatory and antifibrotic microRNA). In conclusion, two distinct histopathological phenotypes based on liver immune phenotyping are observed in SAH patients, suggesting a separate mechanism driving liver injury and/or failure in these patients.
Indexed as
Identifiers
What OpenQuestion holds
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.