Yang M, Olaoba OT, Chinwo SC, LeVasseur H, Zhou B, Kimchi ET, Staveley-O’Carroll KF, Li G. Roles of hepatic immunity in metabolic dysfunction-associated steatotic liver disease: Cellular and molecular mechanisms and clinical trials. World J Gastroenterol 2026; 32(14): 117396 [DOI: 10.3748/wjg.v32.i14.117396]
Corresponding Author of This Article
Guangfu Li, PhD, Professor, Department of Surgery, School of Medicine, University of Connecticut, 263 Farmington Avenue, Farmington, CT 06030, United States. gli@uchc.edu
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Gastroenterology & Hepatology
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Review
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Apr 14, 2026 (publication date) through Apr 3, 2026
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World Journal of Gastroenterology
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1007-9327
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Yang M, Olaoba OT, Chinwo SC, LeVasseur H, Zhou B, Kimchi ET, Staveley-O’Carroll KF, Li G. Roles of hepatic immunity in metabolic dysfunction-associated steatotic liver disease: Cellular and molecular mechanisms and clinical trials. World J Gastroenterol 2026; 32(14): 117396 [DOI: 10.3748/wjg.v32.i14.117396]
World J Gastroenterol. Apr 14, 2026; 32(14): 117396 Published online Apr 14, 2026. doi: 10.3748/wjg.v32.i14.117396
Roles of hepatic immunity in metabolic dysfunction-associated steatotic liver disease: Cellular and molecular mechanisms and clinical trials
Ming Yang, Olamide T Olaoba, Stephanie C Chinwo, Hannah LeVasseur, Beiyan Zhou, Eric T Kimchi, Kevin F Staveley-O’Carroll, Guangfu Li
Ming Yang, Olamide T Olaoba, Stephanie C Chinwo, Eric T Kimchi, Kevin F Staveley-O’Carroll, Guangfu Li, Department of Surgery, School of Medicine, University of Connecticut, Farmington, CT 06030, United States
Olamide T Olaoba, Hannah LeVasseur, Beiyan Zhou, Guangfu Li, Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT 06030, United States
Co-first authors: Ming Yang and Olamide T Olaoba.
Co-corresponding authors: Kevin F Staveley-O’Carroll and Guangfu Li.
Author contributions: Yang M, Olaoba OT and Li G devised the outline; Yang M, Olaoba OT, Chinwo SC, LeVasseur H, Zhou B conducted the literature review; Zhou B, Kimchi ET, Staveley-O’Carroll KF, and Li G critically revised the paper; all authors read and approved the submitted manuscript.
Supported by the National Institutes of Health, No. R01DK130340, No. R01CA274959 and No. R01CA250536.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Corresponding author: Guangfu Li, PhD, Professor, Department of Surgery, School of Medicine, University of Connecticut, 263 Farmington Avenue, Farmington, CT 06030, United States. gli@uchc.edu
Received: December 8, 2025 Revised: December 29, 2025 Accepted: January 27, 2026 Published online: April 14, 2026 Processing time: 118 Days and 13.3 Hours
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common type of chronic liver disease, encompassing a broad spectrum of pathology ranging from hepatic steatosis to metabolic dysfunction-associated steatohepatitis (MASH). Characterized by hepatic inflammation, cell death, and different severities of fibrosis, MASLD can lead to liver cirrhosis and hepatocellular carcinoma (HCC). Although over 100 million people are affected in the United States, effective treatment remains limited, including the only United States Food and Drug Administration-approved resmetirom targeting thyroid hormone receptor-β, which failed to prevent MASLD progression to HCC based on clinic studies. It is necessary and urgent to develop new therapies by advancing the understanding of molecular mechanisms underlying MASLD. Hepatic innate immune cells play an essential role in maintaining liver physiologic homeostasis, as well as actively contributing to MASLD pathogenesis and progression by interacting with liver parenchymal cells and adaptive immune cells in the progression of MASLD and MASH. In this review, we summarize current knowledge about the function of various residential and infiltration innate immune cells in the pathogenesis of MASLD and discuss the molecular mechanisms by which they contribute to liver inflammation, metabolic dysregulation, and fibrogenesis. Additionally, we recapitulate current clinical trials focusing on targeted innate immune cell manipulation and metabolic modulation as therapeutic strategies for MASLD.
Core Tip: Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a broad spectrum of pathology ranging from hepatic steatosis to metabolic dysfunction-associated steatohepatitis (MASH). Effective treatments for MASLD remain limited. Hepatic innate immune cells play an essential role in maintaining liver physiological homeostasis and contributing to MASLD pathogenesis and progression by interacting with liver parenchymal cells and adaptive immune cells in the progression of MASLD and MASH. Treatments targeting innate immune cell manipulation and metabolic modulation, such as fibroblast growth factor 21 analogues, farnesoid X receptor agonists, and chemokine receptor antagonists, can provide therapeutic strategies for MASLD.
