Objective: To investigate the diagnostic value of abnormal serum prothrombin levels in hepatocellular carcinoma (HCC). Methods: A total of 298 patients were diagnosed with HCC at Hunan Provincial People’s Hospital between January 1, 2019, and December 31, 2024, through imaging or liver biopsy, along with 100 patients with cirrhosis, 100 patients with chronic hepatitis B virus infection, and 89 healthy controls, were included in the study. Basic demographic information, as well as levels of abnormal serum prothrombin and alpha-fetoprotein (AFP), were collected. The levels of abnormal serum prothrombin and AFP across the four groups were compared, and their diagnostic efficacy for HCC was analyzed using ROC curve analysis. Results: Abnormal prothrombin levels were significantly higher in the liver cancer group compared to the cirrhosis, hepatitis, and healthy control groups (P < 0.05). No significant differences in abnormal serum prothrombin levels were observed among the cirrhosis, hepatitis, and healthy control groups (P > 0.05). Serum AFP levels were significantly higher in the liver cancer group compared to the cirrhosis, hepatitis, and healthy control groups (P < 0.05) and were higher in the hepatitis group compared to the cirrhosis and healthy control groups (P < 0.05). However, no significant difference in AFP levels was found between the cirrhosis and healthy control groups (P > 0.05). ROC curve analysis indicated that the area under the curve (AUC) for abnormal serum prothrombin and AFP in diagnosing HCC was 0.925 (95% CI: 0.901–0.949) and 0.810 (95% CI: 0.775–0.845), respectively, with sensitivities and specificities of 84% and 75% for abnormal prothrombin and 94% and 76% for AFP. For the diagnosis of AFP-negative HCC, the AUC for abnormal serum prothrombin was 0.838 (95% CI: 0.774–0.901), with a sensitivity and specificity of 65% and 95%, respectively. Conclusion: Serum abnormal prothrombin levels are highly expressed in HCC patients and demonstrate strong diagnostic efficacy for HCC.
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