Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is the 6th most common cancer worldwide and the 4th most common cause of cancer related mortality (Globocan, 2018)
The high risk group, had a sensitivity of (23/33) 69.6% and specificity of (22/22)100% for microvascular invasion (MVI) (P
There were 10 donors with Prothrombin induced by Vitamin K absence-II (PIVKAII) values > 40mAU/ ml but all had values within range reported from United States
Summary
Hepatocellular carcinoma (HCC) is the 6th most common cancer worldwide and the 4th most common cause of cancer related mortality (Globocan, 2018). A small percentage of patients are eligible for curative treatment This is due to advanced tumor stage, degree of liver failure and poor performance status of patients (Bhatti et al, 2016). The sensitivity of AFP is only 40-60% for HCC detection [Heinbach et al, 2018; Gao and Song., 2017) Another biomarker, Protein induced by vitamin K absence-II (PIVKAII) appears to have a promising role in detection and prognosis of HCC. Protein induced by vitamin K absence-II (PIVKAII) appears to have a promising role in detection and prognosis of HCC It has been included in the screening protocols of various guidelines(Ertle et al, 2013; Chinese Society of clinical oncology., 2018). PIVKAII testing was randomly performed in healthy voluntary liver donors to determine normal distribution in our population
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