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

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.