Nicolas Poté1, François Cauchy2, Miguel Albuquerque3, Hélène Voitot4, Jacques Belghiti5, Laurent Castera6, Hervé Puy7, Pierre Bedossa1, Valérie Paradis8. 1. Department of Pathology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France; INSERM UMR 1149, Inflammation Research Center, Paris-Diderot University, Paris, France. 2. INSERM UMR 1149, Inflammation Research Center, Paris-Diderot University, Paris, France; Department of Hepatobiliary Surgery and Liver Transplantation, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France. 3. Department of Pathology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France. 4. Department of Biochemistry, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France. 5. Department of Hepatobiliary Surgery and Liver Transplantation, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France. 6. Department of Hepatology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France. 7. INSERM UMR 1149, Inflammation Research Center, Paris-Diderot University, Paris, France; Department of Biochemistry, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France. 8. Department of Pathology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France; INSERM UMR 1149, Inflammation Research Center, Paris-Diderot University, Paris, France. Electronic address: vparadis@teaser.fr.
Abstract
BACKGROUND & AIMS: Prothrombin induced by vitamin K absence-II (PIVKA-II) is a diagnostic and surveillance marker for HCC mainly used in Asia, and has also been shown to be a predictor of microvascular invasion (MVI), a major prognostic factor in HCC. However, experience with PIVKA-II in Europe remains limited. METHODS: In a French cohort, we conducted a case-control study to compare the performances of α-fetoprotein (AFP) and PIVKA-II serum levels for diagnosis of early stage HCC, and we determined the value of PIVKA-II serum and tissue expression in pre-operative detection of MVI. 43 cirrhotic control patients and 85 HCC cases were included, of which 54 (63.5%) had early stage HCC (n=22 very early, n=32 early). PIVKA-II tissue expression was assessed by immunohistochemistry in HCC surgical samples. RESULTS: For the diagnosis of early HCC, PIVKA-II had a sensitivity of 77% and a specificity of 82% at a cut-off of 42 mAU/ml, vs. 61% and 50% for AFP at a cut-off of 5.5 ng/ml (AUC 0.81 vs. 0.58, respectively). A PIVKA-II level >90 mAU/ml was an independent predictor of MVI (HR 3.5; 95% CI 1.08-11.8; p=0.043). High PIVKA-II tissue expression was significantly associated with the presence of MVI (p=0.001). When combining PIVKA-II immunostaining with the PIVKA-II serum level, sensitivity and specificity for the diagnosis of MVI increased from 70% to 87% and 63% to 90%, respectively. CONCLUSIONS: PIVKA-II was more efficient than AFP for the diagnosis of early HCC, and could be used as a predictive biomarker of MVI.
BACKGROUND & AIMS: Prothrombin induced by vitamin K absence-II (PIVKA-II) is a diagnostic and surveillance marker for HCC mainly used in Asia, and has also been shown to be a predictor of microvascular invasion (MVI), a major prognostic factor in HCC. However, experience with PIVKA-II in Europe remains limited. METHODS: In a French cohort, we conducted a case-control study to compare the performances of α-fetoprotein (AFP) and PIVKA-II serum levels for diagnosis of early stage HCC, and we determined the value of PIVKA-II serum and tissue expression in pre-operative detection of MVI. 43 cirrhotic control patients and 85 HCC cases were included, of which 54 (63.5%) had early stage HCC (n=22 very early, n=32 early). PIVKA-II tissue expression was assessed by immunohistochemistry in HCC surgical samples. RESULTS: For the diagnosis of early HCC, PIVKA-II had a sensitivity of 77% and a specificity of 82% at a cut-off of 42 mAU/ml, vs. 61% and 50% for AFP at a cut-off of 5.5 ng/ml (AUC 0.81 vs. 0.58, respectively). A PIVKA-II level >90 mAU/ml was an independent predictor of MVI (HR 3.5; 95% CI 1.08-11.8; p=0.043). High PIVKA-II tissue expression was significantly associated with the presence of MVI (p=0.001). When combining PIVKA-II immunostaining with the PIVKA-II serum level, sensitivity and specificity for the diagnosis of MVI increased from 70% to 87% and 63% to 90%, respectively. CONCLUSIONS: PIVKA-II was more efficient than AFP for the diagnosis of early HCC, and could be used as a predictive biomarker of MVI.