Cited by 38Liver Disease Diagnosis and TreatmentLiver physiology and pathologyHepatocellular Carcinoma Treatment and Prognosis

The microenvironment in the development of MASLD-MASH-HCC and associated therapeutic in MASH-HCC

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Wu, Qiulin, Yang, Yan, Lin, Shixun, Geller, David A., Yan, Yihe·2025·Frontiers in Immunology

Abstract

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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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
Published
2025-04-30
Volume
16
Pages
1569915-1569915
ISSN
1664-3224 (ISSN-L)
OpenAlex
W4409980710
Cited by
32
References
186
Citations by year
2026: 20 · 2025: 12
FWCI
4.92
Type
journal article
Language
en
Open access
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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