title: Increased von Willebrand factor over decreased ADAMTS13 activity may contribute to the development of liver disturbance and multiorgan failure in patients with alcoholic hepatitis.
abstract: BACKGROUND
  Severe alcoholic hepatitis (SAH) in addition to alcoholic hepatitis (AH) is a life-threatening complication of alcohol abuse, and its pathogenesis remains unclear. The deficiency of ADAMTS13 results in an increase of the plasma unusually large von Willebrand factor multimer (UL-VWFM) and finally causes microcirculatory disturbance and multiorgan failure. We investigated the relationship of ADAMTS13 and von Willebrand factor antigen (VWF:Ag) with the clinical features of AH and SAH.
  
  
  METHODS
  The plasma levels of ADAMTS13 activity, VWF:Ag, and UL-VWFM were determined in 24 patients with AH, 5 with SAH, and 10 with alcoholic liver cirrhosis (LC).
  
  
  RESULTS
  The ADAMTS13 activity was significantly lower in SAH (mean 24%), AH (62%), and LC (76%) than in the healthy subjects (102%, n=62). The VWF:Ag levels were higher in SAH (806%), AH (405%), and LC (514%) than in the healthy subjects (100%), resulting in a higher ratio of VWF:Ag to ADAMTS13 activity in SAH (102.2), AH (8.9), and LC (8.6) compared with the healthy subjects (1.0). In 3 nonsurvivors with SAH and multiorgan failure, the protease activity markedly decreased (from 4.5 to 16%), and VWF:Ag remarkably increased (from 560 to 1,202%), resulting in an extremely high ratio of VWF:Ag to the activity (from 35.0 to 240.4). At the recovery stage in the survivors with SAH and AH, the protease activity increased and the VWF:Ag decreased, whereas in a nonsurvivor with SAH, the activity remained extremely low and the VWF:Ag was still high. Unusually large von Willebrand factor multimer was detected in 80.0% of SAH and 55.6% of AH. Multivariate analysis showed that the serum albumin and platelet count independently correlated with VWF:Ag.
  
  
  CONCLUSIONS
  The enhanced production of UL-VWFM over deficient activity of ADAMTS13 may, in part, contribute to not only the progression of liver injury but also the development of multiorgan failure through microcirculatory disturbance in SAH in addition to AH. The imbalance between the plasma ADAMTS13 activity and VWF:Ag could be a useful prognostic marker in AH.
authors.affiliation: Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Masahito
authors.initials: M
authors.lastname: Uemura
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Ishizashi
authors.forename: Seiji
authors.initials: S
authors.lastname: Kato
authors.forename: Chie
authors.initials: C
authors.lastname: Morioka
authors.forename: Masao
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kojima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshiji
authors.forename: Chikara
authors.initials: C
authors.lastname: Takimura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukui
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000071120:ADAMTS13 Protein; D000328:Adult; D000368:Aged; D000941:Antigens / Q000097:blood*; D005260:Female; D006519:Hepatitis, Alcoholic / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood* / Q000175:diagnosis; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood* / Q000175:diagnosis; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D014841:von Willebrand Factor / Q000276:immunology
chemical_list: D000941:Antigens; C029417:Von Willebrand antigen; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human