Characterization and microRNA Expression Analysis of Serum-Derived Extracellular Vesicles in Severe Liver Injury from Chronic HBV Infection

Min Liu; Xionghao Liu; Mengmeng Pan; Yu Zhang; Xiangling Tang; Wanxi Liu; Mingri Zhao; Jing Ma; Ning Zhou; Yongfang Jiang; Wenlong Wang; Mujun Liu

doi:10.3390/life13020347

Characterization and microRNA Expression Analysis of Serum-Derived Extracellular Vesicles in Severe Liver Injury from Chronic HBV Infection

Life (Basel). 2023 Jan 28;13(2):347. doi: 10.3390/life13020347.

Authors

Min Liu¹, Xionghao Liu^{1

2

3}, Mengmeng Pan¹, Yu Zhang¹, Xiangling Tang¹, Wanxi Liu¹, Mingri Zhao¹, Jing Ma⁴, Ning Zhou⁴, Yongfang Jiang⁴, Wenlong Wang⁴, Mujun Liu^{2

3

5}

Affiliations

¹ Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, China.
² Hunan Key Laboratory of Basic and Applied Hematology, Central South University, Changsha 410078, China.
³ Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha 410078, China.
⁴ Department of Infectious Disease, The Second Xiangya Hospital of Central South University, Changsha 410011, China.
⁵ Department of Cell Biology, School of Life Sciences, Central South University, Changsha 410013, China.

Abstract

Background: Extracellular vesicle (EV) microRNAs have been documented in several studies to have significantly different expressions in hepatitis B virus (HBV)-related liver diseases, such as hepatocellular carcinoma (HCC). The current work aimed to observe the characteristics of EVs and EV miRNA expressions in patients with severe liver injury chronic hepatitis B (CHB) and patients with HBV-associated decompensated cirrhosis (DeCi).

Methods: The characterization of the EVs in the serum was carried out for three different groups, namely, patients with severe liver injury-CHB, patients with DeCi, and healthy controls. EV miRNAs were analyzed using miRNA-seq and RT-qPCR arrays. Additionally, we assessed the predictive and observational values of the miRNAs with significant differential expressions in serum EVs.

Results: Patients with severe liver injury-CHB had the highest EV concentrations when compared to the normal controls (NCs) and patients with DeCi (p < 0.001). The miRNA-seq of the NC and severe liver injury-CHB groups identified 268 differentially expressed miRNAs (|FC| > 2, p < 0.05). In this case, 15 miRNAs were verified using RT-qPCR, and it was found that novel-miR-172-5p and miR-1285-5p in the severe liver injury-CHB group showed marked downregulation in comparison to the NC group (p < 0.001). Furthermore, compared with the NC group, three EV miRNAs (novel-miR-172-5p, miR-1285-5p, and miR-335-5p) in the DeCi group showed various degrees of downregulated expression. However, when comparing the DeCi group with the severe liver injury-CHB group, only the expression of miR-335-5p in the DeCi group decreased significantly (p < 0.05). For the severe liver injury-CHB and DeCi groups, the addition of miR-335-5p improved the predictive accuracy of the serological levels, while miR-335-5p was significantly correlated with ALT, AST, AST/ALT, GGT, and AFP. Conclusions: The patients with severe liver injury-CHB had the highest number of EVs. The combination of novel-miR-172-5p and miR-1285-5p in serum EVs helped in predicting the progression of the NCs to severe liver injury-CHB, while the addition of EV miR-335-5p improved the serological accuracy of predicting the progression of severe liver injury-CHB to DeCi.

Keywords: chronic hepatitis B; cirrhosis liver decompensation; extracellular vesicles; hepatitis B virus; microRNA.

Abstract

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