Abstract
Hepatocellular carcinoma (HCC) early identification is crucial for improving patient outcomes. Current screening methods are often complex and costly. This study developed a simplified, cost-effective HCC screening model using serum marker data. A diverse study population from two Chinese hospitals was recruited, including cancer patients, hospital patients, and healthy individuals. A two-stage screening model was created: LASSO logistic regression for preliminary screening, followed by logistic regression incorporating alpha-fetoprotein (AFP). The model's performance was evaluated in multiple cohorts. Across five populations, the model showed strong performance with AUC-ROC ranging from 0.868 to 0.907, accuracy between 87.43% and 96.96%, and sensitivity over 75% with specificity above 90%. Compared with solely AFP models, the second-stage model improved HCC risk estimates in healthy populations, with significantly higher AUC (0.930 vs. 0.827) and net reclassification improvement (NRI) up to 56.2%. This two-stage model offers a practical, cost-efficient tool for early HCC detection, addressing a significant public health need.