PIVKAII Utility in Diagnosis and Post-therapeutic Monitoring of Hepatocellular Carcinoma

Background: Protein induced by vitamin K absence (PIVKA-II), also known as des-gamma-carboxyprothrombin, has been described in relation to HCC being released in association with vitamin K deficiency in the presence of HCC. Serum alpha-fetoprotein (AFP) is the traditional biomarker for HCC detection and follow up but it doesn’t have high sensitivity and specificity. Therefore, there is great interest in identifying new more powerful biomarkers. Materials and methods: One hundred and fourteen subjects were divided into four groups: Group 1 included 58 patients (38M, 20 F) with HCC, mean age 73.5; Group 2 included 38 patients (28M, 10F) with liver cirrhosis (LC), mean age 63.7; Group 3 included 28 control healthy subjects (25M, 3F), mean age 54.7 and Group 4 included 16 HCC patients (8M, 8F) who underwent to TACE as therapy for HCC. PIVKA II levels were dosed in an overnight fasting blood sample with commercially available chemiluminescent assay (Architect 1000i System, Abbott, USA). Statistical analysis: data were expressed as mean ± SD when distribution was normal, otherwise as median (min-max). Student’s t, Mann Whitney U, Chi-square tests and Pearson linear regression analysis were used when appropriate. Results: PIVKA II levels were higher in HCC group (82.3 mAU/ml) with respect to LC (31.5 mAU/ml) and healthy control (19.7 mAU/ml ) groups and in particular HCC vs controls (p<0.0001), LC vs controls (p<0.0001), HCC vs LC (p<0.005). Moreover, if using a cut off value of 50.9 mAU/ml none in the control group had PIVKA II levels above the cut off, while about 30% of LC and more than 50% of HCC patients had PIVKA II values higher than the cut off. PIVKA II levels in HCC patients who underwent to TACE treatment were higher after the treatment than at baseline. In particular at baseline 31% of HCC patients had PIVKA II levels higher than cut off, while after TACE they became 75% and this behaviour was observed in particular in non responders patients. Conclusions: Our results confirm data from the literature that hypothesize a role for PIVKA II as a better marker than the traditionally used however its role in monitoring the response to therapies needs further evaluations on larger samples