title: Increased plasma levels of high mobility group box 1 in patients with acute liver failure.
abstract: BACKGROUND
  High-mobility group box 1 (HMGB1) is a monocyte-derived late-acting inflammatory mediator, which is released in conditions such as shock, tissue injury and endotoxin-induced lethality. In this study, we determined the plasma and hepatic tissue levels of HMGB1 in patients with acute liver failure (ALF).
  
  
  METHODS
  We determined the plasma levels of HMGB1 and aspartate aminotransferase (AST) in 7 healthy volunteers (HVs), 40 patients with liver cirrhosis (LC), 37 patients with chronic hepatitis (CH), 18 patients with severe acute hepatitis (AH), and 14 patients with fulminant hepatitis (FH). The 14 patients with FH were divided into two subgroups depending upon the history of plasma exchange (PE) before their plasma sample collection. The hepatic levels of HMGB1 were measured in tissue samples from 3 patients with FH who underwent living-donor liver transplantation and from 3 healthy living donors. Hepatic tissue samples were also subjected to immunohistochemical examination for HMGB1.
  
  
  RESULTS
  The plasma levels of HMGB1 (ng/ml) were higher in patients with liver diseases, especially in FH patients with no history of PE, than in HVs (0.3 ± 0.3 in HVs, 4.0 ± 2.0 in LC, 5.2 ± 2.6 in CH, 8.6 ± 4.8 in severe AH, 7.8 ± 2.7 in FH with a history of PE, and 12.5 ± 2.6 in FH with no history of PE, p < 0.05 in each comparison). There was a strong and statistically significant relationship between the mean plasma HMGB1 level and the logarithm of the mean AST level (R = 0.900, p < 0.05). The hepatic tissue levels of HMGB1 (ng/mg tissue protein) were lower in patients with FH than in healthy donors (539 ± 116 in FH vs. 874 ± 81 in healthy donors, p < 0.05). Immunohistochemical staining for HMGB1 was strong and clear in the nuclei of hepatocytes in liver sections from healthy donors, but little staining in either nuclei or cytoplasm was evident in specimens from patients with FH.
  
  
  CONCLUSIONS
  We confirmed that plasma HMGB1 levels were increased in patients with ALF. Based on a comparison between HMGB1 contents in normal and ALF livers, it is very likely that HMGB1 is released from injured liver tissue.
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Oshima
authors.forename: M
authors.initials: M
authors.lastname: Shinoda
authors.forename: M
authors.initials: M
authors.lastname: Tanabe
authors.forename: H
authors.initials: H
authors.lastname: Ebinuma
authors.forename: R
authors.initials: R
authors.lastname: Nishiyama
authors.forename: K
authors.initials: K
authors.lastname: Takano
authors.forename: S
authors.initials: S
authors.lastname: Yamada
authors.forename: T
authors.initials: T
authors.lastname: Miyasho
authors.forename: Y
authors.initials: Y
authors.lastname: Masugi
authors.forename: S
authors.initials: S
authors.lastname: Matsuda
authors.forename: K
authors.initials: K
authors.lastname: Suda
authors.forename: K
authors.initials: K
authors.lastname: Fukunaga
authors.forename: K
authors.initials: K
authors.lastname: Matsubara
authors.forename: T
authors.initials: T
authors.lastname: Hibi
authors.forename: H
authors.initials: H
authors.lastname: Yagi
authors.forename: T
authors.initials: T
authors.lastname: Hayashida
authors.forename: Y
authors.initials: Y
authors.lastname: Yamagishi
authors.forename: H
authors.initials: H
authors.lastname: Obara
authors.forename: O
authors.initials: O
authors.lastname: Itano
authors.forename: H
authors.initials: H
authors.lastname: Takeuchi
authors.forename: S
authors.initials: S
authors.lastname: Kawachi
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Hibi
authors.forename: I
authors.initials: I
authors.lastname: Maruyama
authors.forename: Y
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D001219:Aspartate Aminotransferases / Q000097:blood; D024243:HMGB1 Protein / Q000097:blood*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000473:pathology; D017114:Liver Failure, Acute / Q000097:blood* / Q000473:pathology
chemical_list: D024243:HMGB1 Protein; D001219:Aspartate Aminotransferases