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

Wenyan Zhang; Jing Zhang; Honglin Shi; Fang Liu; Haibin Yu; Hongbo Shi

doi:10.1007/s12072-023-10520-1

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

Hepatol Int. 2023 Oct;17(5):1170-1181. doi: 10.1007/s12072-023-10520-1. Epub 2023 Jun 6.

Authors

Wenyan Zhang^#^{1

2

3}, Jing Zhang^#⁴, Honglin Shi^{1

5}, Fang Liu^{1

5}, Haibin Yu⁶, Hongbo Shi^{7

8}

Affiliations

¹ Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China.
² State Clinical Drug Trial Institute, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China.
³ Department of Infectious Diseases, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450000, China.
⁴ The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China.
⁵ Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer, Beijing, 100069, China.
⁶ State Clinical Drug Trial Institute, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China. dryuhaibin@ccmu.edu.cn.
⁷ Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China. shihongbo@ccmu.edu.cn.
⁸ Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer, Beijing, 100069, China. shihongbo@ccmu.edu.cn.

^# Contributed equally.

PMID: 37278869
DOI: 10.1007/s12072-023-10520-1

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.

Keywords: Biomarkers; Exosomes; Fibrosis; Glucose transporter 1 (GLUT1); Non-alcoholic fatty liver disease (NAFLD).

MeSH terms

Biomarkers
Biopsy / methods
Exosomes* / pathology
Fibrosis
Glucose Transporter Type 1
Hepatocytes / pathology
Humans
Liver / pathology
Liver Cirrhosis / pathology
Non-alcoholic Fatty Liver Disease* / pathology

Substances

Glucose Transporter Type 1
Biomarkers

Abstract

MeSH terms

Substances

Grants and funding