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Citations to this article

Distinct histopathological phenotypes of severe alcoholic hepatitis suggest different mechanisms driving liver injury and failure
Jing Ma, … , Suthat Liangpunsakul, Bin Gao
Jing Ma, … , Suthat Liangpunsakul, Bin Gao
Published July 15, 2022
Citation Information: J Clin Invest. 2022;132(14):e157780. https://doi.org/10.1172/JCI157780.
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Research Article Gastroenterology Article has an altmetric score of 25

Distinct histopathological phenotypes of severe alcoholic hepatitis suggest different mechanisms driving liver injury and failure

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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.

Authors

Jing Ma, Adrien Guillot, Zhihong Yang, Bryan Mackowiak, Seonghwan Hwang, Ogyi Park, Brandon J. Peiffer, Ali Reza Ahmadi, Luma Melo, Praveen Kusumanchi, Nazmul Huda, Romil Saxena, Yong He, Yukun Guan, Dechun Feng, Pau Sancho-Bru, Mengwei Zang, Andrew MacGregor Cameron, Ramon Bataller, Frank Tacke, Zhaoli Sun, Suthat Liangpunsakul, Bin Gao

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Total citations by year

Year: 2025 2024 2023 2022 Total
Citations: 10 14 11 3 38
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2023 (11)

Title and authors Publication Year
Monocyte-derived macrophages orchestrate multiple cell types to repair necrotic liver lesions
Dechun Feng, Xiaogang Xiang, Yukun Guan, Adrien Guillot, Hongkun Lu, Chingwen Chang, Yong He, Hua Wang, Hongna Pan, Cynthia Ju, Sean Colgan, Frank Tacke, XinWei Wang, George Kunos, Bin Gao
Journal of Clinical Investigation 2023
Alcohol ingestion promotes CGRP-dependent lung fibrosis by the induction of innate lymphoid cells in mice
Liang Chen, Rui Sun, Chao Lei, Zhishan Xu, Yong Song, Zhongbin Deng
Frontiers in immunology 2023
The Roles of Myeloid Cells in Aging-related Liver Diseases
Yao J, Li Y, Wang H
International journal of biological sciences 2023
Experimental models of fatty liver diseases: Status and appraisal
Wang H, Shen H, Seo W, Hwang S
Hepatology Communications 2023
Hepatic inflammatory responses in liver fibrosis.
Hammerich L, Tacke F
Nature reviews. Gastroenterology & hepatology 2023
The intersection between alcohol-related liver disease and nonalcoholic fatty liver disease.
Díaz LA, Arab JP, Louvet A, Bataller R, Arrese M
Nature reviews. Gastroenterology & hepatology 2023
Ambiguous Pathogenic Roles of Macrophages in Alcohol-Associated Liver Diseases
Ait Ahmed Y, Lafdil F, Tacke F
Hepatic medicine : evidence and research 2023
Unraveling the Complex Interplay between Epigenetics and Immunity in Alcohol-Associated Liver Disease: A Comprehensive Review
Liu Y, Liu T, Zhang F, Gao Y
International journal of biological sciences 2023
Activation of cholangiocyte mTORC1 drives alcohol-induced ductular reaction
Mackowiak B, Gao B
Hepatology 2023
Novel treatment of acute and acute-on-chronic liver failure: Interleukin-22.
Hwang S, Hicks A, Hoo CZ, Kwon YS, Cho YE, Moore J, Gao B
Liver international : official journal of the International Association for the Study of the Liver 2023
Cell-Specific Regulation of Inflammatory Cytokines and Acute-Phase Proteins by the Glucocorticoid Receptor
Winkler R, Lu H
Mediators of Inflammation 2023

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