Combined serum IFN-γ and IL-22 levels as predictive biomarkers for hepatocellular carcinoma risk: A clinical investigation.

Hepatocellular carcinoma (HCC) is predominantly diagnosed at advanced stages due to a lack of reliable biomarkers for early detection. Consequently, identifying predictive biomarkers for HCC development in patients with chronic liver diseases holds significant potential for improving early diagnosis and clinical outcomes of this aggressive malignancy. Serum levels of immune checkpoint proteins and cytokines were quantified by ELISA in patients with chronic hepatitis B, liver cirrhosis, and HCC, with healthy subjects serving as controls. Cytokine profiles were compared between patients with HCC and without HCC using one-way ANOVA and multivariate logistic regression. The diagnostic performance of interferon (IFN)-γ, interleukin (IL)-22, and α-fetoprotein (AFP) was evaluated by receiver operating characteristic (ROC) curve analysis. The serum levels of programmed cell death protein 1 and programmed death-ligand 1 progressively increased with advancing stages of liver disease. IFN-γ emerged as a protective factor against HCC [odds ratio (OR)=0.991; 95% CI, 0.984-0.997], while IL-22 was identified as a risk factor (OR=1.020, 95% CI, 1.004-1.036). The combined evaluation of IFN-γ and IL-22 demonstrated superior diagnostic accuracy [area under the curve (AUC)=0.863; 95% CI, 0.755-0.971] compared with AFP alone (AUC=0.644; 95% CI, 0.483-0.804). The combination of IFN-γ and IL-22 exhibited enhanced diagnostic performance compared with AFP alone in predicting and detecting early-stage HCC, suggesting its potential utility as a novel biomarker panel for HCC screening.