HCC-Check: A Novel Diagnostic Tool for Early Detection of Hepatocellular Carcinoma Based on Cytokeratin-1 and Epithelial Membrane Antigen: A Cross-Sectional Study.

Background: Hepatocellular carcinoma is frequently diagnosed in advanced stages, leading to a poorer prognosis. Therefore, early diagnosis and identification of biomarkers may significantly improve outcomes. Methods: This cross-sectional study enrolled 486 participants distributed among 3 groups: F1 to F3 = 184, F4 = 183, and hepatocellular carcinoma = 119. Liver fibrosis staging was performed using FibroScan, while imaging features were used for hepatocellular carcinoma detection. Epithelial membrane antigen and cytokeratin-1 levels in serum were quantified through Western blot and ELISA, respectively. Results: Patients diagnosed with hepatocellular carcinoma exhibited significantly elevated levels of epithelial membrane antigen and cytokeratin-1 compared to non-hepatocellular carcinoma patients, with a highly significant statistical difference (P < .0001). Epithelial membrane antigen demonstrated diagnostic performance with an area under the curve of 0.75, a sensitivity of 69.0%, and a specificity of 68.5%. Cytokeratin-1 for the identification of hepatocellular carcinoma showed a sensitivity of 79.0% and a specificity of 81.4%, resulting in an area under the curve of 0.87. The developed HCC-Check, which incorporates epithelial membrane antigen, cytokeratin-1, albumin, and alpha-fetoprotein, displayed a higher area under the curve of 0.95 to identify hepatocellular carcinoma, with a sensitivity of 89.8% and a specificity of 83.9%. Notably, HCC-Check values exceeding 2.57 substantially increased the likelihood of hepatocellular carcinoma, with an estimated odds ratio of 50.65, indicating a higher susceptibility to hepatocellular carcinoma development than those with lower values. The HCC-Check diagnostic test exhibited high precision in identifying patients with hepatocellular carcinoma, particularly those with small tumor sizes (<5 cm) and a single nodule, as reflected in area under the curve values of 0.92 and 0.85, respectively. HCC-Check was then applied to the validation study to test its accuracy and reproducibility, showing superior area under the curves for identifying different stages of hepatocellular carcinoma. These outcomes underscore the effectiveness of the test in the early detection of hepatocellular carcinoma. Conclusion: The HCC-Check test presents a highly accurate diagnostic method for detecting hepatocellular carcinoma in its early stages.