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MicroRNA-223-3p levels in serum-derived extracellular vesicles predict regression of M2BPGi-based liver fibrosis after hepatitis C virus eradication by direct-acting antiviral agents

  • Original Article―Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

We retrospectively investigated microRNA (miRNA) levels in serum-derived extracellular vesicles (EVs) as predictive indicators for regression of liver fibrosis, after achievement of a sustained virological response (SVR) by direct-acting antiviral (DAA) therapy for chronic hepatitis C (CHC).

Methods

The study subjects were recruited from a historical cohort of 108 CHC patients whose pretreatment serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels were ≥ 2.0 cut-off index (COI). We classified patients with M2BPGi levels < 1.76 and ≥ 1.76 COI at 2 years after the end of treatment (EOT) into the regression and non-regression groups, respectively. Eleven of the patients were assigned to the discovery set, and we comprehensively investigated the miRNAs contained in serum-derived EVs at 24 weeks after the EOT (EOT24W), using RNA sequencing. The remaining 97 patients were assigned to the validation set, and reproducibility was verified by quantitative real-time PCR.

Results

Through analysis of the discovery and validation sets, we identified miR-223-3p and miR-1290 as candidate predictors. Subsequently, we analyzed various clinical data, including these candidate miRNAs. Multivariate analyses revealed that the levels of miR-223-3p at EOT24W were significantly associated with regression of M2BPGi-based liver fibrosis (Odds ratio: 1.380; P = 0.024). Consistent results were obtained, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis (pretreatment M2BPGi levels ≥ 3.3 COI).

Conclusions

The miR-223-3p level in serum-derived EVs at EOT24W is a feasible predictor of regression of M2BPGi-based liver fibrosis after achievement of an SVR by DAA therapy.

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Abbreviations

M2BPGi:

Binding protein glycosylation isomer

CHC:

Chronic hepatitis C

COI:

Cut-off index

DAA:

Direct antiviral agent

EV:

Extracellular vesicle

SVR:

Sustained virological response

EOT:

End of treatment

EOT24W:

24 Weeks after the EOT

MiRNA:

MicroRNA

ALBI:

Albumin–bilirubin

FIB-4:

Fibrosis-4

T-Bil:

Total bilirubin

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Acknowledgements

We thank Sachiko Sakata for keeping samples

Funding

This research was supported by the Japan Agency for Medical Research and Development (AMED) (Grant number JP24fk0210113) and the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant numbers: JP17K09435 and JP20K08314 to Kentaro Matsuura).

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Authors and Affiliations

  1. Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho, Nagoya, Aichi, 467-8601, Japan

    Takanori Suzuki, Kentaro Matsuura, Hayato Kawamura, Kei Fujiwara & Hiromi Kataoka

  2. Department of Gastroenterology, Kasugai Municipal Hospital, Kasugai, Japan

    Yoshihito Nagura

  3. Department of Virology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Kyoko Ito

  4. Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

    Shintaro Ogawa, Katsuya Nagaoka, Etsuko Iio, Takehisa Watanabe & Yasuhito Tanaka

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Contributions

Conception and design: Takanori Suzuki, and Kentaro Matsuura; drafting of manuscript: Takanori Suzuki, and Kentaro Matsuura; acquisition, analysis and interpretation of data: Takanori Suzuki, Kentaro Matsuura, Yoshihito Nagura, Shintaro Ogawa, Hayato Kawamura, Kei Fujiwara, Katsuya Nagaoka, Etsuko Iio, Takehisa Watanabe, Hiromi Kataoka, and Yasuhito Tanaka; critical revision of the manuscript: Takanori Suzuki, and Kentaro Matsuura; study supervision: Hiromi Kataoka and Yasuhito Tanaka.

Corresponding author

Correspondence to Kentaro Matsuura.

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Conflict of interest

Yasuhito Tanaka: Research funding from Gilead Sciences, Fujirebio, Inc., AbbVie GK, Board of Trustees of the Leland Stanford Junior University. Lecture fees from Gilead Sciences, Fujirebio, Inc., AbbVie GK. The editorial board member of Hepatology Research.

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Suzuki, T., Matsuura, K., Nagura, Y. et al. MicroRNA-223-3p levels in serum-derived extracellular vesicles predict regression of M2BPGi-based liver fibrosis after hepatitis C virus eradication by direct-acting antiviral agents. J Gastroenterol (2024). https://doi.org/10.1007/s00535-024-02115-w

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