title: Performance of PIVKA-II for early hepatocellular carcinoma diagnosis and prediction of microvascular invasion.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pathology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France; INSERM UMR 1149, Inflammation Research Center, Paris-Diderot University, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Poté
authors.affiliation: 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.
authors.forename: François
authors.initials: F
authors.lastname: Cauchy
authors.affiliation: Department of Pathology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France.
authors.forename: Miguel
authors.initials: M
authors.lastname: Albuquerque
authors.affiliation: Department of Biochemistry, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Voitot
authors.affiliation: Department of Hepatobiliary Surgery and Liver Transplantation, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Belghiti
authors.affiliation: Department of Hepatology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Castera
authors.affiliation: INSERM UMR 1149, Inflammation Research Center, Paris-Diderot University, Paris, France; Department of Biochemistry, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Puy
authors.affiliation: Department of Pathology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France; INSERM UMR 1149, Inflammation Research Center, Paris-Diderot University, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bedossa
authors.affiliation: 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.
authors.forename: Valérie
authors.initials: V
authors.lastname: Paradis
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000473:pathology; D016022:Case-Control Studies; D057186:Comparative Effectiveness Research; D055088:Early Detection of Cancer; D005260:Female; D005602:France; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000097:blood / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011379:Prognosis; D011498:Protein Precursors / Q000097:blood / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D012372:ROC Curve; D012680:Sensitivity and Specificity; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D011516:Prothrombin
keywords: Alpha fetoprotein; Diagnosis; Hepatocellular carcinoma; Microvascular invasion; Prothrombin induced by vitamin K absence-II