Combining AFP, PIVKA-II, and GP73 has diagnostic utility for hepatitis B-associated hepatocellular carcinoma and is consistent with liver pathology results.

Although liquid biopsy has garnered increasing attention in recent years for diagnosing hepatocellular carcinoma (HCC), serum biomarkers continue to hold significant value for HCC diagnosis due to their simple operation, cost-effectiveness, and high efficiency. This study aimed to screen for the optimal diagnostic combinations of alpha fetoprotein (AFP), a protein induced by vitamin K deficiency or antagonist II (PIVKA-II), golgi glycoprotein 73 (GP73), and routine clinical indicators for diagnosing hepatitis B-associated HCC (HBV-HCC). A retrospective analysis was conducted on 358 HBV-HCC patients treated at Taizhou People's Hospital from August 2015 to October 2021; 124 patients with chronic hepatitis B (CHB) and 241 patients with hepatitis B cirrhosis composed the control group. With liver pathology as the gold standard, the concordance between the screened indicators and liver pathology for HCC diagnosis was analyzed by Cohen's kappa coefficient. In the CHB group, AFP, PIVKA-II, and GP73 were statistical significance, and the triple biomarker combination achieved the highest AUC (0.908) for HCC diagnosis, surpassing the efficacy of both individual indicators and two biomarker combinations. In both the Child‒Pugh A and Child‒Pugh B&C cirrhosis groups, AFP and PIVKA-II were significantly different between patients with and without HCC, and the AUC values of AFP combined with PIVKA-II for HCC diagnosis were 0.969 and 0.956, respectively. Using liver pathology as the gold standard, the Kappa values of the above combinations in the three groups were 0.866, 0.780, and 0.800, respectively. The triple combination of AFP, PIVKA-II, and GP73 in the CHB group and the combination of AFP and PIVKA-II in both the Child‒Pugh A and Child‒Pugh B&C cirrhosis groups had excellent diagnostic accuracy for HCC, consistent with liver pathology, and were superior to the diagnostic ability of individual biomarkers.