Mingxia Shou, Rui Shen, Guoqian Xiang, Yulin Wu, Qinghui Xia
Early detection of hepatocellular carcinoma (HCC) remains limited by the incomplete sensitivity of alpha-fetoprotein (AFP), especially in early-stage and AFP-negative tumors. This study evaluated whether abnormal prothrombin/protein induced by vitamin K absence-II (PIVKA-II), AFP, and routine clinical variables could be integrated into a reproducible diagnostic model for HCC. A retrospective training cohort of 205 participants, including 112 imaging-confirmed HCC cases and 93 non-HCC controls, was used for model development. An independent prospective validation cohort of 184 participants, including 58 HCC cases and 126 non-HCC controls, was used for out-of-sample testing without model refitting. Pre-imaging blood samples were used for AFP and PIVKA-II measurement, and clinical variables were extracted from the same diagnostic window. The final multivariable logistic-regression model combined ln(AFP), ln(PIVKA-II), age, sex, albumin, international normalized ratio, and platelet count. The combined model achieved an AUC of 0.93 in the training cohort and 0.89 in the validation cohort. In validation, sensitivity was 84.5% and specificity was 90.5%. Sensitivity remained 72.7% in early-stage HCC and 73.1% in AFP-negative HCC, exceeding AFP alone in both subgroups. Calibration and bootstrap validation supported acceptable model stability. These results show how PIVKA-II, AFP, and routinely available clinical variables can be combined into a practical diagnostic triage tool for high-risk liver disease populations.