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Peer-reviewedCC BY-NC-ND 4.0Digestive and Liver Disease

Circulating hepatocyte-derived extracellular particles as potential biomarker of steatohepatitis progression to fibrogenesis: Exploring the impact of smoking

Abstract

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) encompasses a spectrum of liver conditions, primarily driven by metabolic factors and characterized by steatosis. Extracellular vesicles and particles (EVPs) are emerging as biomarkers for liver diseases as they reflect the state of their cells of origin and carry molecular cargo that can influence disease progression. We aimed to explore the role of EVPs with MASLD progression, smoking impact and EVPs effect on macrophages.Methods: We analyzed EVPs using nanoparticle tracking analysis, transmission electron microscopy and flow cytometry. Cytokine expressions were quantified in EVPs-exposed macrophages.Results: We showed that EVP number is higher in patients with steatohepatitis and they were correlated with the severity of liver inflammation and steatosis, as well as with biological markers. In particular CD63+-ASGR1+-EVPs were notably more prevalent in blood of patients with steatohepatitis. Active smoking further increased EVP numbers and CD63+-ASGR1+-EVPs in MASLD patients. Functionally, exposure of macrophages to CD63+-EVPs from MASLD patients induced TGF-β and TIMP-1 secretion.Conclusion: This study highlights the potential of EVs as biomarkers for MASLD progression and their role in mediating disease mechanisms via intercellular communication, notably by their potential to contribute to fibrogenic signaling. Although exploratory, the study also highlights the potential impact of the exposome, particularly smoking, on MASLD pathogenesis.

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BibTeX
@article{masrour2026circulating,
  title = {{Circulating hepatocyte-derived extracellular particles as potential biomarker of steatohepatitis progression to fibrogenesis: Exploring the impact of smoking}},
  author = {Oumnia Masrour and J Morvan and Alison Rapin and Alexis Aimé and Agnès Burel and Valentine Genet and Stéphanie Brisset and Dominique Lagadic-Gossmann and Edouard Bardou-Jacquet and Corinne Martin-Chouly},
  journal = {Digestive and Liver Disease},
  year = {2026},
  month = oct,
  doi = {10.1016/j.dld.2025.12.003},
  url = {https://hal.science/hal-05493354v1},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Circulating hepatocyte-derived extracellular particles as potential biomarker of steatohepatitis progression to fibrogenesis: Exploring the impact of smoking
AU  - Oumnia Masrour
AU  - J Morvan
AU  - Alison Rapin
AU  - Alexis Aimé
AU  - Agnès Burel
AU  - Valentine Genet
AU  - Stéphanie Brisset
AU  - Dominique Lagadic-Gossmann
AU  - Edouard Bardou-Jacquet
AU  - Corinne Martin-Chouly
PY  - 2026
DA  - 2026/10/13
JO  - Digestive and Liver Disease
DO  - 10.1016/j.dld.2025.12.003
UR  - https://hal.science/hal-05493354v1
AB  - Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) encompasses a spectrum of liver conditions, primarily driven by metabolic factors and characterized by steatosis. Extracellular vesicles and particles (EVPs) are emerging as biomarkers for liver diseases as they reflect the state of their cells of origin and carry molecular cargo that can influence disease progression. We aimed to explore the role of EVPs with MASLD progression, smoking impact and EVPs effect on macrophages.Methods: We analyzed EVPs using nanoparticle tracking analysis, transmission electron microscopy and flow cytometry. Cytokine expressions were quantified in EVPs-exposed macrophages.Results: We showed that EVP number is higher in patients with steatohepatitis and they were correlated with the severity of liver inflammation and steatosis, as well as with biological markers. In particular CD63+-ASGR1+-EVPs were notably more prevalent in blood of patients with steatohepatitis. Active smoking further increased EVP numbers and CD63+-ASGR1+-EVPs in MASLD patients. Functionally, exposure of macrophages to CD63+-EVPs from MASLD patients induced TGF-β and TIMP-1 secretion.Conclusion: This study highlights the potential of EVs as biomarkers for MASLD progression and their role in mediating disease mechanisms via intercellular communication, notably by their potential to contribute to fibrogenic signaling. Although exploratory, the study also highlights the potential impact of the exposome, particularly smoking, on MASLD pathogenesis.
SN  - 1590-8658
ER  -