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Introduction <p>Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in patients with acute-on-chronic liver failure (ACLF). Cytokines play essential roles in the pathogenesis of IPA and have been identified as promising diagnostic biomarkers. This study aimed to conduct a comprehensive proof-of-concept evaluation of the diagnostic potential of cytokines for IPA in patients with ACLF.</p> Methods <p>In this single-center prospective study, patients with HBV-ACLF were categorized into IPA (with diagnostic criteria of probable IPA, <i>n</i> = 16), bacterial pneumonia (BP, <i>n</i> = 32), and non-infection (<i>n</i> = 32) groups. Groups were matched for age, gender, and liver decompensation severity. Plasma cytokines, interleukin (IL)-33, IL-17A, IL-23, IL-31, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, interferon-γ, tumor necrosis factor alpha, and soluble IL-2 receptor, were quantified. Diagnostic accuracy was assessed via ROC analysis.</p> Results <p>IL-33 levels were markedly elevated in IPA vs. BP (163.07 [108.30–211.22] vs. 12.82 [4.24–50.55]&#xa0;pg/mL; <i>P</i> &lt; 0.001) and non-infection groups (163.07 [108.30–211.22] vs. 4.24 [4.24–52.51]&#xa0;pg/mL; <i>P</i> &lt; 0.001). ROC analysis identified IL-33 as a strong diagnostic marker for IPA (AUC =&#xa0;0.871; sensitivity 93.80%, specificity 84.40%; <i>P</i> &lt; 0.001) with optimal cutoff at 66.97&#xa0;pg/mL. Furthermore, IL-33 levels were significantly elevated during IPA development compared to both the incubation phase (154.86 vs. 8.29&#xa0;pg/mL, <i>P</i> = 0.005) and the recovery phase (154.86 vs. 28.01&#xa0;pg/mL, <i>P</i> = 0.038).</p> Conclusions <p>Plasma IL-33 demonstrates high accuracy in diagnosing IPA and differentiating it from bacterial infections in patients with HBV-ACLF, offering a minimally invasive diagnostic tool.</p> <p>Graphical abstract available for this article.</p> Graphical Abstract <p></p>

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Novel Diagnostic Marker Interleukin-33 for Invasive Pulmonary Aspergillosis in Acute-on-Chronic Liver Failure: A Proof-of-Concept Prospective Study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月24日

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  • Lanyue Huang,
  • Meng Zhang,
  • Wei Liu,
  • Yunhui Liu,
  • Liang Chen,
  • Yuxin Niu,
  • Yuzhao Feng,
  • Qiuyu Cheng,
  • Tingting Liu,
  • Peng Wang,
  • Mi Song,
  • Guang Chen,
  • Lin Zhu,
  • Tao Chen,
  • Qin Ning

摘要

Introduction

Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in patients with acute-on-chronic liver failure (ACLF). Cytokines play essential roles in the pathogenesis of IPA and have been identified as promising diagnostic biomarkers. This study aimed to conduct a comprehensive proof-of-concept evaluation of the diagnostic potential of cytokines for IPA in patients with ACLF.

Methods

In this single-center prospective study, patients with HBV-ACLF were categorized into IPA (with diagnostic criteria of probable IPA, n = 16), bacterial pneumonia (BP, n = 32), and non-infection (n = 32) groups. Groups were matched for age, gender, and liver decompensation severity. Plasma cytokines, interleukin (IL)-33, IL-17A, IL-23, IL-31, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, interferon-γ, tumor necrosis factor alpha, and soluble IL-2 receptor, were quantified. Diagnostic accuracy was assessed via ROC analysis.

Results

IL-33 levels were markedly elevated in IPA vs. BP (163.07 [108.30–211.22] vs. 12.82 [4.24–50.55] pg/mL; P < 0.001) and non-infection groups (163.07 [108.30–211.22] vs. 4.24 [4.24–52.51] pg/mL; P < 0.001). ROC analysis identified IL-33 as a strong diagnostic marker for IPA (AUC = 0.871; sensitivity 93.80%, specificity 84.40%; P < 0.001) with optimal cutoff at 66.97 pg/mL. Furthermore, IL-33 levels were significantly elevated during IPA development compared to both the incubation phase (154.86 vs. 8.29 pg/mL, P = 0.005) and the recovery phase (154.86 vs. 28.01 pg/mL, P = 0.038).

Conclusions

Plasma IL-33 demonstrates high accuracy in diagnosing IPA and differentiating it from bacterial infections in patients with HBV-ACLF, offering a minimally invasive diagnostic tool.

Graphical abstract available for this article.

Graphical Abstract