Effectiveness of PIVKA-II in the detection of hepatocellular carcinoma based on real-world clinical data

Abstract

BackgroundProtein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) is an efficient biomarker specific for hepatocellular carcinoma (HCC). Some researchers have proved that levels of PIVKA-II reflect HCC oncogenesis and progression. However, the effectiveness of PIVKA-II based on real-world clnical data has barely been studied.MethodsA total of 14,861 samples were tested in Southwest Hospital in over 2 years’ time. Among them, 4073 samples were PIVKA-II positive. Finally, a total of 2070 patients with at least two image examinations were enrolled in this study. Levels of AFP and PIVKA-II were measured by chemiluminescence enzyme immunoassay (CLEIA) and chemiluminescent microparticle Immunoassay (CMIA), respectively.ResultsA total of 1016 patients with HCC were detected by PIVKA-II in a real-world application. In all these cases, 88.7% cases primarily occurred and patients with advanced HCC covered 61.3%. Levels of PIVKA-II were significantly higher in advanced group (4650.0 mAU/ml, 667.0–33,438.0 mAU/ml) than early-stage group (104.5 mAU/ml, 61.0–348.8 mAU/ml; P < 0.001). Levels of PIVKA-II elevated significantly in recurrence and residual group than recovery group (P < 0.001). A total of 1054 PIVKA-II positive patients were non-HCC cases. Among them, cirrhosis took the largest part (46.3%), followed by hepatitis (20.6%) and benign nodules (15.3%). High-levels of PIVKA-II in at-risk patients is an indicator of HCC development in two-year time.ConclusionsOur data showed that PIVKA-II effectively increases the detection rate of HCC was a valid complement to AFP and image examination in HCC surveillance.

Transient increases in serum α fetoprotein and protein induced by vitamin K antagonist II levels following proton therapy does not necessarily indicate progression of hepatocellular carcinoma

“…As the combination of PIVKA-II and AFP may increase sensitivity without decreasing specificity, the guidelines of the Japan Society of Hepatology recommended to measure these biomarkers during HCC surveillance (10). A recent study showed that the tumor markers might elevate at 0.5-1.5 years before the HCC lesion becomes obvious on diagnostic imaging (23). Furthermore, AFP and PIVKA-II elevation may suggest micrometastases, which may result in early recurrence within weeks or months after primary treatment (21,24).…”

Biomarkers in Diagnosis and Prediction of Hepatocellular Carcinoma Recurrence (Review)

“…Des-gamma carboxyprothrombin may be used to assess not only the risk of HCC development but to predict its recurrence after surgical treatment. In the prospective study [107], application of DCP with AFP made it possible to suspect HCC 2 years before the diagnose verification. Further investigations are necessary in order to evaluate the effectiveness of this marker combination in the diagnosis of HCC [44].…”

Hepatocellular Carcinoma: Known and Emerging Risk Factors

“…PIVKA-II is considered a suitable serum marker of HCC due to its high specificity. Thanks to the development of accurate measuring methods, Japanese Society Hepatology (JSH) recommends it as a marker of surveillance for HCC hepatitis, steatosis, benign nodules, liver abscess, pregnancy) [127]. Furthermore, an Italian observational cohort study in patients with US evidence of liver nodules, shows a higher specificity and positive predictive value (PPV) of PIVKA-II as compared to αFP; furthermore, the combined use of PIVKA-II and αFP improves the diagnostic accuracy as compared to either PIVKA-II or αFPalone (Table 1) [128].…”