Clinical Utility of Protein Induced by Vitamin K Absence-II in Patients with Hepatocellular Carcinoma

OBJECTIVE: Despite moderate sensitivity, alpha fetoprotein (AFP) is widely used in screening and prognostication for hepatocellular carcinoma (HCC). The objective of the current study was to assess clinical utility of Prothrombin induced by Vitamin K absence-II (PIVKAII) in addition to AFP in patients with HCC. METHODS: We retrospectively reviewed 244 patients with documented AFP, PIVKA II and dynamic imaging of the liver. Using ROC curves, cutoff values for AFP and PIVKAII for HCC detection, tumor grade and microvascular invasion (MVI) were assessed. In patients who underwent liver transplantation (LT) for HCC, survival was determined using Kaplan Meier curves. RESULTS: The median PIVKAII in healthy living donors was 28.6mAU/ml (15.9-55). In cirrhotics, the sensitivity of an AFP cutoff of 7.6 ng/ml or PIVKAII cutoff of 250 mAU/ml for HCC detection was 91.7% (176/192) and specificity was 62.9%(68/108) (P<0.0001). In patients with HCC, PIVKAII values were significantly elevated with tumor size > 5 cm (P < 0.0001), tumor nodules > 3(P=0.01), and macrovascular invasion(P<0.0001). The high risk group (patients with AFP ≥ 40 ng/ml + PIVKAII ≥ 350 mAU/ml), had a sensitivity of (23/33) 69.6% and specificity of (22/22)100% for MVI (P <0.001). The estimated 3 year RFS after LT in the low risk group (AFP <40 ng/ml or PIVKAII< 350 mAU/ml) was 100% versus 63%(P=0.001). The estimated 3 year RFS based with and without MVI was 80% and 100% (P=0.03). CONCLUSION: PIVKAII in combination with AFP, appears to have a promising role in surveillance and prognostication for HCC. It also allows improved patient selection for liver transplantation.