title: Time-dependent analysis of predisposing factors for the recurrence of hepatocellular carcinoma.
abstract: OBJECTIVE
  There are many reports dealing with the risk factors for hepatocellular carcinoma (HCC) recurrence. However, in most of these reported studies, factors were analysed only at the initial treatment stage, and the predisposing factors for the recurrence during follow-up have not been well studied. The aim of this study is to evaluate the predisposing factors after treatments.
  
  
  METHODS
  Two hundred and seventy-one consecutive HCC patients curatively treated between January 1994 and March 2004 were followed up and analysed. The recurrence rate was estimated by the Kaplan- Meier method and the predisposing factors were evaluated by time-fixed Cox regression analysis and by time-dependent covariate analysis using multiple parameters.
  
  
  RESULTS
  The mean follow-up period was 4.86 years and recurrence was observed in 169 patients (62.4%). The recurrence rates were 27.9, 65.1 and 84.3% at 1, 3 and 5 years respectively. Among the variables determined before treatment, predisposing factors for recurrence were low serum albumin [< or =3.5 g/dl, hazard ratio (HR)=1.47, 95% confidence interval (CI)=1.07-2.01] and multiple tumour number (HR=2.04, 95% CI=1.46-2.84) by time-fixed multivariate analysis. In the time-dependent analysis, six variables with 12 013 plots were examined. The multivariate analysis revealed that high des- gamma-carboxy prothrombin (DCP > or =40 mAU/ml, HR=2.33, 95% CI=1.61-3.39), high alpha-fetoprotein (AFP > or =100 ng/ml, HR=2.01, 95% CI=1.3-3.35) and high alanine aminotransferase (ALT > or = 40 IU/L, HR= 1.52, 95% CI=1.1-2.1) were significant predisposing factors for recurrence.
  
  
  CONCLUSIONS
  Predisposing factors for the recurrence of HCC after treatment are different from those before treatments and special cautions are required when AFP, DCP or ALT is high during follow-up.
authors.affiliation: Department of Internal Medicine, Hiroshima City Hospital, Hiroshima, Japan.
authors.forename: Shouta
authors.initials: S
authors.lastname: Iwadou
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nouso
authors.forename: Kenji
authors.initials: K
authors.lastname: Kuwaki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakamura
authors.forename: Hironori
authors.initials: H
authors.lastname: Tanaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miyake
authors.forename: Hidenori
authors.initials: H
authors.lastname: Shiraha
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shiratori
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D016016:Proportional Hazards Models; D011498:Protein Precursors / Q000097:blood*; D011516:Prothrombin; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: C097353:AFP protein, human; D015415:Biomarkers; D014408:Biomarkers, Tumor; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D011516:Prothrombin; D000410:Alanine Transaminase