ObjectiveTo explore the predictive value of serum prothrombin induced by vitamin K absence-Ⅱ (PIVKA-Ⅱ) detection for the biological characteristics of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).MethodsThis retrospective study included 394 patients with HBV-related HCC who were newly diagnosed and treated with surgical resection in West China Hospital of Sichuan University between June 2017 and December 2018. Their clinical information such as tumor size, tumor number, tumor cell differentiation, presence of microvascular invasion (MVI), distant metastasis, and portal vein tumor thrombus was collected from the medical record. The laboratory test results of patients during diagnosis and before surgery were collected, including alpha-fetoprotein (AFP), PIVKA-Ⅱ, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (γ-GGT), etc., and the relationships between PIVKA-Ⅱ levels and tumor biological characteristics were analyzed. Non-normal continuous variables were presented as medium (lower quartile, upper quartile).ResultsCompared with the patients with low HCC serum PIVKA-Ⅱ levels (≤40 mAU/mL), patients with high serum PIVKA-Ⅱ levels (>40 mAU/mL) had larger tumor diameters [5.00 (3.00, 9.00) vs. 2.50 (1.63, 4.95) cm, P<0.001], more severe Barcelona Clinic Liver Cancer (BCLC) stage (P<0.001), and higher AFP [186.05 (6.86, 1 210.00) vs. 17.83 (4.33, 231.95) ng/mL, P<0.001], ALT [38.00 (26.00, 66.25) vs. 32.00 (22.00, 51.00) U/L, P=0.018], AST [42.00 (30.00, 76.00) vs. 34.00 (25.50, 48.25) U/L, P<0.001], and γ-GGT [71.00 (39.00, 165.50) vs. 55.50 (25.00, 93.00) U/L, P=0.005], and were more likely to form portal vein tumor thrombi (16.61% vs. 3.75%, P=0.003) and MVI (43.67% vs. 11.11%, P<0.001). In BCLC stage 0 HCC patients, the positive rate of PIVKA-Ⅱ was only 51.35%. Multivariate logistic regression analysis showed that PIVKA-Ⅱ>40 mAU/mL was an independent predictor of MVI [odds ratio=6.588, 95% confidence interval (CI) (1.645, 26.383), P=0.008]. The area under receiver operating characteristic curve of PIVKA-Ⅱ level predicting MVI was 0.761 [95%CI (0.693, 0.830)], with a sensitivity of 66.22% and a specificity of 79.06%.ConclusionIn HBV-related HCC patients, high PIVKA-Ⅱ is associated with the poor biological characteristics of tumor, and is an independent risk factor for tumor MVI.