title: Prediction of hepatocellular carcinoma development by plasma ADAMTS13 in chronic hepatitis B and C.
abstract: BACKGROUND
  Chronic liver injury evokes a wound healing response, promoting fibrosis and finally hepatocellular carcinoma (HCC), in which hepatic stellate cells play an important role. Although a blood marker of hepatic stellate cells is not known, those cells importantly contribute to the regulation of plasma a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) activity, a defect of which causes thrombotic thrombocytopenic purpura.
  
  
  METHODS
  Plasma ADAMTS13 was evaluated in chronic hepatitis B or C patients with or without HCC.
  
  
  RESULTS
  Plasma ADAMTS13 activity significantly correlated with serum aspartate aminotransferase and alanine aminotransferase, liver stiffness value, and aspartate aminotransferase-to-platelet ratio index, irrespective of the presence of HCC, suggesting that it may reflect hepatocellular damage and subsequent wound healing and fibrosis as a result of hepatic stellate cell action. During the three-year follow-up period for patients without HCC, it developed in 10 among 81 patients. Plasma ADAMTS13 activity was significantly higher in patients with HCC development than in those without and was a significant risk for HCC development by univariate and multivariate analyses. Furthermore, during the one-year follow-up period for patients with HCC treated with radiofrequency ablation, HCC recurred in 55 among 107 patients. Plasma ADAMTS13 activity or antigen level was significantly higher in patients with HCC recurrence than in those without and was retained as a significant risk for HCC recurrence by multivariate analysis.
  
  
  CONCLUSIONS
  Higher plasma ADAMTS13 activity and antigen level was a risk of HCC development in chronic liver disease.
  
  
  CONCLUSIONS
  Plasma ADAMTS13 as a potential marker of hepatic stellate cells may be useful in the prediction of hepatocarcinogenesis.
authors.affiliation: Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan. ikeda-1im@h.u-tokyo.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ikeda
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tateishi
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Enooku
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Yoshida
authors.forename: Hayato
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Ryota
authors.initials: R
authors.lastname: Masuzaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kondo
authors.forename: Tadashi
authors.initials: T
authors.lastname: Goto
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Shiina
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kume
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Tomiya
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Inoue
authors.forename: Takako
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Natsuko
authors.initials: N
authors.lastname: Ohtomo
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tanoue
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ono
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yatomi
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000071120:ADAMTS13 Protein; D000368:Aged; D000410:Alanine Transaminase / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000302:isolation & purification; D055166:Hepatic Stellate Cells / Q000378:metabolism; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000821:virology; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human