Diagnostic and Prognostic Value of Combined Detection of Serum Protein Induced by Vitamin K Absence or Antagonist-II, Alpha-Fetoprotein, and Spliced Hepatitis B Virus in Hepatitis B Virus-Induced Hepatocellular Carcinoma.

Objective: To demonstrate the diagnostic and prognostic value of combined detection of serum abnormal prothrombin II (PIVKA II), α-fetoprotein (AFP), and spliced variants of hepatitis B virus genomes (spHBV) in HBV-induced hepatocellular carcinoma (HCC). Materials and Methods: From March 2018 to May 2019, samples were collected from 125 patients with HBV-related hepatocellular carcinoma (HBV-HCC), 125 patients with pure HBV (HBV group), and 125 patients with HBV-induced cirrhosis (HBV cirrhosis group), all of whom were receiving treatment at the hospital. Serum levels of PIVKA-II, AFP, and spHBV were measured using an immunochemiluminescence detection system, a fully automated immunoassay analyzer, and a real-time quantitative polymerase chain reaction instrument, respectively. Kaplan-Meier method was applied to analyze relationship among serum PIVKA-II, AFP, spHBV, and prognosis of patients with HBV-HCC; cyclooxygenase (COX) risk regression analyzed factors affecting prognosis of patients with HBV-HCC; receiver operating characteristic (ROC) curve evaluated diagnostic and prognostic predictive efficacy of serum PIVKA-II, AFP, and spHBV alone or combined for HBV-HCC. Results: The serum concentrations of PIVKA-II, AFP, and spHBV in the HBV-HCC group were significantly higher than those in the HBV cirrhosis group and the HBV group (all p < 0.05). The HBV cirrhosis group also showed significantly higher levels compared with the HBV group (p < 0.05). Serum PIVKA-II, AFP, spHBV, tumor number, tumor-node-metastasis (TNM) stage, and extrahepatic metastasis differed markedly between dead patients and surviving patients (p < 0.05). PIVKA-II, AFP, and spHBV in patients with HBV-HCC were related to tumor number, TNM staging, and extrahepatic metastasis (p < 0.05).The 36-month survival rate of patients with high-expression PIVKA-II was inferior to patients with low expression (χ² = 6.561, p = 0.010); the 36-month survival rate of patients with high-expression AFP was inferior to patients with low expression (χ² = 4.789, p = 0.029); and the 36-month survival rate of patients with high-expression spHBV was inferior to patients with low expression (χ² = 5.761, p = 0.016). Multivariate logistic regression analysis showed that high expression of PIVKA-II, AFP, spHBV in serum, multiple tumors, TNM staging of stage III-IV, and extrahepatic metastasis were all risk factors for death in patients with HBV-HCC (p < 0.05). The area under the curve (AUC) of the combination of serum PIVKA-II, AFP, and spHBV in the diagnosis for HBV-HCC was markedly higher than PIVKA-II, AFP, and spHBV alone diagnosis (p < 0.05). The AUC predicted by the combination of serum PIVKA-II, AFP, and spHBV in predicting the prognosis of patients with HBV-HCC was markedly higher than that predicted by the three factors alone (p < 0.05). Conclusions: Serum PIVKA-II, AFP, and spHBV joint detection has significant clinical value for diagnosis and prognosis of HBV-HCC.