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In logistic regression analysis, IL-27 20.79 pg/mL was an independent risk factor for HCE biological viability with receiver operating characteristic analysis at a 44.23 pg/mL cut-off resulting in 0.72 area under the curve. Our findings correlate multiple cytokine and chemokine secretion patterns in HAE and HCE patients with different disease progression stages. IL-27 could serve as a referring biomarker for distinguishing HCE biological viability and provide a preliminary foundation for clinical decision-making. Our findings correlate