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Hepatocyte-derived exosome may be as a biomarker of liver regeneration and prognostic valuation in patients with acute-on-chronic liver failure

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Abstract

Background

The assessment of liver regeneration is particularly critical for patients with acute-on-chronic liver failure (ACLF). Exosome has both the advantages of specificity of liver biopsy and noninvasion of peripheral blood, which may be the potential biomarker of liver disease.

Methods

The patients with chronic hepatitis B (CHB) and ACLF were enrolled from outpatients and inpatients in Beijing Youan Hospital, Capital Medical University. The exosomes in plasma were extracted by ultracentrifuge using Optima XPN-100 Ultracentrifuge. Exosomes were dyed with fluorescent direct-labeled antibody and the expression profile was assayed using ImageStream® X MKII Imaging Flow Cytometer.

Results

The percentage of exosomes with ALB and CD63 was significant higher in ACLF than that in CHB. The percentage of exosomes with ALB and CD63 and VEGF increased in CHB, but decreased in ACLF. The exosomes with ALB, CD63, and VEGF were significant more in survival group than that in dead group in patients with ACLF. The sensitivity and specificity of exosomes with CD63, ALB, and VEGF were significantly higher than the other markers of liver regeneration and prognostic valuation in patients with ACLF including AFP. The hepatocyte-derived exosomes expression profile had no difference in different stages and different AFP levels of patients with ACLF.

Conclusion

The exosomes profile with ALB and VEGF may be a more accurate and specific biomarker of liver regeneration and prognostic valuation than AFP in patients with ACLF. In addition, the exosomes profile with CD63 and ALB may be an early-warning marker in patients with ACLF.

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Funding

This study was funded by Beijing municipal medical research institute public welfare development and reform pilot project (jingyiyan2019-6); The National Natural Science Foundation of China (81672026); the Chinese Foundation for Hepatitis Prevention and Control (TQGB20190050 and 2020033).

Author information

Author notes

  1. Yan Jiao and Wang Lu contributed to this study equally.

Authors and Affiliations

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

    Yan Jiao, Ping Xu, Honglin Shi, Dexi Chen, Hongbo Shi & Yingmin Ma

  2. Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, 100069, China

    Wang Lu & Yu Chen

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

    Yan Jiao, Ping Xu, Honglin Shi, Dexi Chen, Hongbo Shi & Yingmin Ma

Authors
  1. Yan Jiao
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Contributions

YJ performed the experiments and analyzed the data. WL and YC enrolled the patients and provided specimens. PX participated in the collection of specimens. HS carried out routine maintenance and repair of the image flow cytometry. HS designed the study and wrote the paper. DC, YC, YM reviewed and edited the paper.

Corresponding authors

Correspondence to Yu Chen, Hongbo Shi or Yingmin Ma.

Ethics declarations

Conflict of interest

All authors (Yan Jiao, Wang Lu, Ping Xu, Honglin Shi, Dexi Chen, Yu Chen, Hongbo Shi, Yingmin Ma) have no conflicts of interest to declare.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Supplementary Information

Below is the link to the electronic supplementary material.

12072_2021_10217_MOESM1_ESM.tif

Supplementary file1 Supplement.1. The subgroup analysis of hepatocyte-derived exosome in different stages of patients with ACLF. (A) The image of exosomes with CD63 and ALB in different stages of patients with ACLF by image flow cytometry. (B) The percentage of exosomes with CD63 and ALB in different stages of patients with ACLF by image flow cytometry. (C) The comparison of exosomes with CD63 and ALB in different stages of patients with ACLF. (D) The image of exosomes with CD63 and ALB and VEGF in different stages of patients with ACLF by image flow cytometry. (E) The percentage of exosomes with CD63 and ALB and VEGF in different stages of patients with ACLF by image flow cytometry. (F) The comparison of exosomes with CD63 and ALB and VEGF in different stages of patients with ACLF. *indicated P<0.05, **indicated P<0.01. (TIF 19564 KB)

12072_2021_10217_MOESM2_ESM.tif

Supplementary file2 Supplement.2. The subgroup analysis of hepatocyte-derived exosome in different AFP levels of patients with ACLF. (A) The image of exosomes with CD63 and ALB in different AFP levels of patients with ACLF by image flow cytometry. (B) The percentage of exosomes with CD63 and ALB in different AFP levels of patients with ACLF by image flow cytometry. (C) The comparison of exosomes with CD63 and ALB in different AFP levels of patients with ACLF. (D) The image of exosomes with CD63 and ALB and VEGF in different AFP levels of patients with ACLF by image flow cytometry. (E) The percentage of exosomes with CD63 and ALB and VEGF in different AFP levels of patients with ACLF by image flow cytometry. (F) The comparison of exosomes with CD63 and ALB and VEGF in different AFP levels of patients with ACLF. *indicated P<0.05, **indicated P<0.01. (TIF 19573 KB)

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Jiao, Y., Lu, W., Xu, P. et al. Hepatocyte-derived exosome may be as a biomarker of liver regeneration and prognostic valuation in patients with acute-on-chronic liver failure. Hepatol Int 15, 957–969 (2021). https://doi.org/10.1007/s12072-021-10217-3

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  • DOI: https://doi.org/10.1007/s12072-021-10217-3

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