title: Prognostic values of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II in hepatitis B virus-related hepatocellular carcinoma: a prospective study.
abstract: OBJECTIVE
  Alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) are most widely used tumor markers in detecting hepatocellular carcinoma (HCC). Recently, there have been some studies about them as prognostic markers in hepatitis C virus-associated HCC. However, prognostic values of AFP and PIVKA-II remain clarified in hepatitis B virus (HBV)-associated HCC. This study was aimed to evaluate the prognostic values of AFP and PIVKA-II in HBV-associated HCC.
  
  
  METHODS
  Patients (n=126) were divided into 4 groups according to median levels of AFP and PIVKA-II (L; low/low, A; high/low, P; low/high, H; high/high) at diagnosis. Clinical characteristics and survival were compared among the groups, and Cox regression analysis was performed to find independent factors for survival.
  
  
  RESULTS
  Baseline host and viral factors were not significantly different among the 4 groups. High PIVKA-II groups (P and H) had more aggressive tumor characteristics (larger size of tumors, higher number of tumors, frequent portal vein thrombosis, P<0.05) and much shorter median survival time than low PIVKA-II groups (L and A) (P<0.05). In multivariate analysis, high PIVKA-II level was an independent predictor for survival (risk ration: 2.377, 95% confidence interval: 1.359-4.157, P=0.002) together with Child-Pugh score, advanced TMN stages, and treatment modality. Even after excluding 33 patients who had Child-Pugh class C and advanced tumor stages (tumor-nodes-metastasis stage III-IV) at diagnosis, high PIVKA-II level was still an independent predictor for survival (risk ration: 4.258, 95% confidence interval: 2.418-8.445, P<0.001).
  
  
  CONCLUSIONS
  Serum PIVKA-II level, not serum AFP, was a valuable independent prognostic factor in HBV-related HCC.
authors.affiliation: Department of Internal Medicine, Kangdong Sacred Heart Hospital of Hallym University Medical Center, Seoul, Republic of Korea.
authors.forename: Hyoung Su
authors.initials: HS
authors.lastname: Kim
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Park
authors.forename: Ji Sun
authors.initials: JS
authors.lastname: Jang
authors.forename: Ha Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Woon Geon
authors.initials: WG
authors.lastname: Shin
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Kim
authors.forename: Jin Heon
authors.initials: JH
authors.lastname: Lee
authors.forename: Hak Yang
authors.initials: HY
authors.lastname: Kim
authors.forename: Myoung Kuk
authors.initials: MK
authors.lastname: Jang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000628:therapy / Q000821:virology; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000628:therapy / Q000821:virology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D011516:Prothrombin; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000032:analysis*
chemical_list: C097353:AFP protein, human; D015415:Biomarkers; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D011516:Prothrombin