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Background <p>We investigated serum-derived extracellular vesicle (EV)-associated proteins as predictors of liver fibrosis (LF) regression following sustained virological responses (SVR) in individuals with chronic hepatitis C (CHC) managed using direct-acting antiviral (DAA) therapy.</p> Methods <p>We retrospectively analyzed 107 CHC patients with pretreatment Mac-2 binding protein glycosylation isomer (M2BPGi) levels ≥ 2.0 cut-off index (COI). Two years after the end of treatment (EOT), participants were grouped according to the M2BPGi levels: regression group (M2BPGi &lt; 1.76 COI) and non-regression group (M2BPGi ≥ 1.76 COI). Twelve patients were selected for the discovery cohort, where comprehensive protein profiling of serum-derived EVs was performed at 12–24&#xa0;weeks post-EOT using quantitative mass spectrometry for label-free quantification. The remaining 95 patients formed the validation group, in which the identified EV proteins were further assessed via protein quantification using parallel reaction monitoring.</p> Results <p>Reelin (RELN) and oncoprotein-induced transcript 3 (OIT3) protein had potential role as predictors of fibrosis regression in both groups. Multivariate analysis incorporating clinical parameters indicated that levels of RELN and OIT3 were associated with fibrosis regression (odds ratio [OR] = 1.510; <i>P</i> = 0.022 for log<sub>2</sub> RELN, and OR = 0.297; <i>P</i> = 0.001 for log<sub>2</sub> OIT3). In cases with advanced fibrosis (baseline M2BPGi ≥ 3.3 COI), RELN showed a borderline significant result (OR = 1.550; <i>P</i> = 0.050 for log<sub>2</sub> RELN).</p> Conclusions <p>Serum-derived EV levels of RELN show promise as predictor of LF regression in CHC patients following SVR.</p>

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Reelin level in serum-derived extracellular vesicles predicts regression of M2BPGi-defined liver fibrosis following hepatitis C virus eradication by direct-acting antiviral agents

  • 期刊论文

  • 发表日期：

    2026年5月30日

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  • Takanori Suzuki,
  • Kentaro Matsuura,
  • Yutaka Hashimoto,
  • Masako Okina,
  • Mayumi Hojo,
  • Hayato Kawamura,
  • Kei Fujiwara,
  • Katsuya Nagaoka,
  • Takehisa Watanabe,
  • Hiromi Kataoka,
  • Yasuhito Tanaka

摘要

Background

We investigated serum-derived extracellular vesicle (EV)-associated proteins as predictors of liver fibrosis (LF) regression following sustained virological responses (SVR) in individuals with chronic hepatitis C (CHC) managed using direct-acting antiviral (DAA) therapy.

Methods

We retrospectively analyzed 107 CHC patients with pretreatment Mac-2 binding protein glycosylation isomer (M2BPGi) levels ≥ 2.0 cut-off index (COI). Two years after the end of treatment (EOT), participants were grouped according to the M2BPGi levels: regression group (M2BPGi < 1.76 COI) and non-regression group (M2BPGi ≥ 1.76 COI). Twelve patients were selected for the discovery cohort, where comprehensive protein profiling of serum-derived EVs was performed at 12–24 weeks post-EOT using quantitative mass spectrometry for label-free quantification. The remaining 95 patients formed the validation group, in which the identified EV proteins were further assessed via protein quantification using parallel reaction monitoring.

Results

Reelin (RELN) and oncoprotein-induced transcript 3 (OIT3) protein had potential role as predictors of fibrosis regression in both groups. Multivariate analysis incorporating clinical parameters indicated that levels of RELN and OIT3 were associated with fibrosis regression (odds ratio [OR] = 1.510; P = 0.022 for log2 RELN, and OR = 0.297; P = 0.001 for log2 OIT3). In cases with advanced fibrosis (baseline M2BPGi ≥ 3.3 COI), RELN showed a borderline significant result (OR = 1.550; P = 0.050 for log2 RELN).

Conclusions

Serum-derived EV levels of RELN show promise as predictor of LF regression in CHC patients following SVR.