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Exosome GLUT1 derived from hepatocyte identifies the risk of non-alcoholic steatohepatitis and fibrosis

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Abstract

Background and aims

It is particularly important to identify the progression of non-alcoholic fatty liver disease (NAFLD) for prognosis evaluation and treatment guidance. The aim of this study was to explore the clinic use of exosomal protein-based detection as a valuable non-invasive diagnostic method for NAFLD.

Methods

Exosomes were extracted from plasma of patients with NAFLD using Optima XPN-100 ultrafast centrifuge. The patients were recruited from outpatients and inpatients of Beijing Youan Hospital Affiliated to Capital Medical University. The exosomes were stained with fluorescent-labeled antibody and determined by ImageStream® X MKII imaging flow cytometry. Generalized linear logistic regression model was used to evaluate the diagnostic value of hepatogenic exosomes in NAFLD and liver fibrosis.

Results

The percentage of hepatogenic exosomes glucose transporter 1 (GLUT1) in patients with non-alcoholic steatohepatitis (NASH) was significantly higher than that in patients with non-alcoholic fatty liver (NAFL). According to liver biopsy, we found that the percentage of hepatogenic exosomes GLUT1 in patients with advanced NASH (F2-4) was significantly higher than that in patients with early NASH (F0-1), and the same trend was observed in exosomes with CD63 and ALB. Compared with other clinical fibrosis scoring criteria (FIB-4, NFS, etc.), the diagnostic performance of hepatogenic exosomes GLUT1 was the highest and the area under the receiver-operating curves (AUROC) was 0.85 (95% CI 0.77–0.93). Furthermore, the AUROC of hepatogenic exosomes GLUT1 combined with fibrosis scoring was as high as 0.86–0.91.

Conclusion

Hepatogenic exosome GLUT1 can be a molecular biomarker for early warning of NAFLD to distinguish the NAFL and NASH, and it also can be used as a novel non-invasive diagnostic biomarker for the staging liver fibrosis in NAFLD.

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Data availability

The data used or analyzed during this study are included in this article and available from the corresponding author upon reasonable request.

Abbreviations

NAFLD:

Non-alcoholic fatty liver disease

NASH:

Non-alcoholic steatohepatitis

NAFL:

Non-alcoholic fatty liver

GLUT1:

Glucose transporter 1

ALB:

Serum albumin

FIB4:

Fibrosis-4

NFS:

NAFLD fibrosis score

APRI:

Aspartate aminotransferase to platelet ratio index

BARD:

BMI aspartate aminotransferase/alanine aminotransferase ratio diabetes

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Acknowledgements

This study was funded by Beijing Natural Science Foundation (M22030), Beijing Municipal Medical Research Institute Public Welfare Development and Reform Pilot Project (jingyiyan2019-6, jingyiyan2021-10), and the Chinese Foundation for Hepatitis Prevention and Control (TQGB20190050 and 2020033).

Funding

The authors have not disclosed any funding.

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Author notes

  1. Wenyan Zhang and Jing Zhang: both authors are contributed equally to this study.

Authors and Affiliations

  1. Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China

    Wenyan Zhang, Honglin Shi, Fang Liu & Hongbo Shi

  2. State Clinical Drug Trial Institute, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China

    Wenyan Zhang & Haibin Yu

  3. Department of Infectious Diseases, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450000, China

    Wenyan Zhang

  4. The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China

    Jing Zhang

  5. Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer, Beijing, 100069, China

    Honglin Shi, Fang Liu & Hongbo Shi

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  1. Wenyan Zhang
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Correspondence to Haibin Yu or Hongbo Shi.

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Wenyan Zhang, Jing Zhang, Honglin Shi, Fang Liu, Haibin Yu, and Hongbo Shi have no conflicts of interest to declare.

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Zhang, W., Zhang, J., Shi, H. et al. Exosome GLUT1 derived from hepatocyte identifies the risk of non-alcoholic steatohepatitis and fibrosis. Hepatol Int 17, 1170–1181 (2023). https://doi.org/10.1007/s12072-023-10520-1

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  • DOI: https://doi.org/10.1007/s12072-023-10520-1

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