The microenvironment in the development of MASLD-MASH-HCC and associated therapeutic in MASH-HCC
Open accessAbstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a series of obesity-related metabolic liver diseases, ranging from relatively benign hepatic steatosis to metabolic-associated steatohepatitis (MASH). With the changes in lifestyle, its incidence and prevalence have risen to epidemic proportions globally. In recent years, an increasing amount of evidence has indicated that the hepatic microenvironment is involved in the pathophysiological processes of MASH-induced liver fibrosis and the formation of hepatocellular carcinoma (HCC). The hepatic microenvironment is composed of various parenchymal and non-parenchymal cells, which communicate with each other through various factors. In this review, we focus on the changes in hepatocytes, cholangiocytes, liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs), Kupffer cells (KC), dendritic cells (DC), neutrophils, monocytes, T and B lymphocytes, natural killer cells (NK), natural killer T cells (NKT), mucosal-associated invariant T cells (MAIT), γδT cells, and gut microbiota during the progression of MASLD. Furthermore, we discuss promising therapeutic strategies targeting the microenvironment of MASLD-MASH-HCC.
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The results extend current MASLD frameworks into an integrated mechanical-metabolic-inflammatory axis.
“our results extend current MASLD frameworks, traditionally centered on metabolic dysregulation and inflammation, into an integrated mechanical–metabolic–inflammatory axis [44, 45, 46, 47, 48]”
From Liver Stiffness Rises Early in MASLD and Drives Inflammation, Lipid Dysmetabolism, and Fibrosis via Piezo1–YAP Mechanotransduction (2026) · cites this paper as [47]
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Targeting NFATc4 attenuates non-alcoholic steatohepatitis in mice
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Inhibition of Secretin/Secretin Receptor Axis Ameliorates NAFLD Phenotypes
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The effect of feeding and fasting on fenestrations in the liver sinusoidal endothelial cell
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Sterile inflammation in MASH: emerging role of extracellular RNA and therapeutic strategies
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TET3 is a common epigenetic immunomodulator of pathogenic macrophages
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- Authors
- Wu, Q., Yang, Y., Lin, S., Geller, D. A., & Yan, Y.
- Affiliations
- Guangxi Medical University (CN)
- University of Pittsburgh Medical Center (US)
- Corresponding author
- Geller, David A.
- Yan, Yihe
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2025-04-30
- Volume
- 16
- Pages
- 1569915-1569915
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC12074932
- OpenAlex
- W4409980710
- Cited by
- 32
- References
- 186
- Citations by year
- 2026: 20 · 2025: 12
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82360526)
- Natural Science Foundation of Guangxi Province
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK120531)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Keywords
- non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, hepatocellular carcinoma, hepatic microenvironment, liver fibrosis, liver sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells, dendritic cells, neutrophils, T cells, natural killer cells, NKT cells, mucosal-associated invariant T cells, γδ T cells, gut microbiota, obesity, treatment options
- MeSH terms
- Gastrointestinal Microbiome, Animals, Fatty Liver, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Tumor Microenvironment, Non-alcoholic Fatty Liver Disease
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