Abstract:Objective To explore the clinical diagnostic value of combined serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ), hepatic fibrosis 4 index (FIB-4) and tyrosine urine test (TUT) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods Fifty patients with HBV-related HCC, 50 patients with HBV-related benign liver diseases and 50 healthy people in the First Hospital of Changsha from January 2021 to December 2022 were selected as the study subjects. The differences of serum AFP, PIVKA-Ⅱ, FIB-4, and the positive rates of TUT among three groups were compared. The area under the receiver operating characteristic curve (AUC) of individual detection and combined detection in the diagnosis of HCC were analyzed, and the clinical application value of combined detection in the diagnosis of HBV-related HCC was evaluated. Results The levels of serum AFP, PIVKA-Ⅱ, FIB-4 and the positive rate of TUT among three groups were significantly different (P＜0.05). The levels of AFP, PIVKA-Ⅱ, FIB-4 and the positive rate of TUT in the HBV-related HCC were higher than those in the healthy control group (P＜0.05). The levels of AFP, PIVKA-Ⅱ and the positive rate of TUT in the HBV-related HCC group were higher than those in the HBV-related benign liver disease group (P＜0.05), but there was no significant difference in FIB-4 (P＞0.05). The levels of PIVKA-Ⅱ and FIB-4 in HBV-related benign liver disease group were significantly higher than those in healthy control group (P＜0.05), while the levels of serum AFP and the positive rates of TUT were not significantly different (P＞0.05). Receiver operating characteristic (ROC) curve analysis showed that the AUC of AFP, PIVKA-Ⅱ, FIB-4 and TUT were 0.812, 0.827, 0.722 and 0.761, respectively. The best cut-off values of serum AFP, PIVKA-Ⅱ and FIB-4 for diagnosing HCC were 21.1 ng/mL, 41.32 mAU/mL and 3.27, respectively. In the single test for diagnosis of HBV-related HCC, the TUT had the highest sensitivity of 82.00% and the AFP had the highest specificity of 95.00%. In the combined test for diagnosis of HBV-related HCC, the serum AFP+PIVKA-Ⅱ+FIB-4+TUT had the maximum AUC of 0.935 and the highest sensitivity of 90.00%, while AFP+PIVKA-Ⅱ+FIB-4 had the highest specificity of 97.00%. Conclusion The combined test of serum AFP, PIVKA-Ⅱ, FIB-4 and TUT can improve the diagnostic efficacy of HCC and has a significant clinical value in the early diagnosis of HBV-related HCC.