title: Protein induced by vitamin K absence or antagonist-II production is a strong predictive marker for extrahepatic metastases in early hepatocellular carcinoma: a prospective evaluation.
abstract: BACKGROUND
  Clinicians often experience extrahepatic metastases associated with hepatocellular carcinoma (HCC), even if no evidence of intrahepatic recurrence after treatment is observed. We investigated the pretreatment predictors of extrahepatic metastases in HCC patients.
  
  
  METHODS
  Patients diagnosed with HCC without evidence of extrahepatic metastases were prospectively enrolled. We evaluated the correlation between extrahepatic metastases and pretreatment clinical variables, including serum tumor markers.
  
  
  RESULTS
  A total of 354 patients were included. Seventy-six patients (21%) had extrahepatic metastases during the observation period (median, 25.3 months; range, 0.6-51.3 months). Cox regression multivariate analysis showed that serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) production levels, the intrahepatic tumor stage, platelet count, and portal vein thrombosis were independent risk factors for extrahepatic metastases. Patients with a PIVKA-II production ≥ 300 mAU/mL had a 2.7-fold (95% confidence interval; 1.5-4.8; P < 0.001) and 3.7-fold (95% confidence interval; 2.0-6.6; P < 0.001) increased risk for extrahepatic metastases after adjustment for stage, platelet count, alpha-fetoprotein ≥ 400 ng/mL, and portal vein thrombosis according to the AJCC and BCLC staging systems, respectively.
  
  
  CONCLUSIONS
  PIVKA-II production levels might be a good candidate predictive marker for extrahepatic HCC metastases, especially in patients with smaller and/or fewer tumors in the liver with in stages regardless of serum alpha-fetoprotein.
authors: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
authors: Hyun-Mi
authors: HM
authors: Bae
authors: Jeong-Hoon
authors: JH
authors: Lee
authors: Jung-Hwan
authors: JH
authors: Yoon
authors: Yoon Jun
authors: YJ
authors: Kim
authors: Dae Seog
authors: DS
authors: Heo
authors: Hyo-Suk
authors: HS
authors: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D011516:Prothrombin; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D011516:Prothrombin