Increased plasma levels of high mobility group box 1 in patients with acute liver failure

Go Oshima, Masahiro Shinoda, M. Tanabe, H. Ebinuma, R. Nishiyama, K. Takano, S. Yamada, T. Miyasho, Yohei Masugi, Satoru Matsuda, K. Suda, Koichi Fukunaga, Kentaro Matsubara, T. Hibi, Hiroshi Yagi, Tetsu Hayashida, Y. Yamagishi, Hideaki Obara, O. Itano, H. Takeuchi & 5 others S. Kawachi, Hidetsugu Saito, T. Hibi, I. Maruyama, Yuukou Kitagawa

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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). Patients and 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)154-162
Number of pages9
JournalEuropean Surgical Research
Volume48
Issue number3
DOIs
Publication statusPublished - 2012 Jun

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Acute Liver Failure
Hepatitis
Plasma Exchange
Liver
Healthy Volunteers
Living Donors
Tissue Donors
Chronic Hepatitis
Aspartate Aminotransferases
Liver Cirrhosis
Staining and Labeling
Endotoxins
Liver Transplantation
Liver Diseases
Monocytes
Hepatocytes
Shock
Cytoplasm

Keywords

  • Acute liver failure
  • Fulminant hepatitis
  • High-mobility group box 1
  • Human
  • Liver transplantation

ASJC Scopus subject areas

  • Surgery

Cite this

Increased plasma levels of high mobility group box 1 in patients with acute liver failure. / Oshima, Go; Shinoda, Masahiro; Tanabe, M.; Ebinuma, H.; Nishiyama, R.; Takano, K.; Yamada, S.; Miyasho, T.; Masugi, Yohei; Matsuda, Satoru; Suda, K.; Fukunaga, Koichi; Matsubara, Kentaro; Hibi, T.; Yagi, Hiroshi; Hayashida, Tetsu; Yamagishi, Y.; Obara, Hideaki; Itano, O.; Takeuchi, H.; Kawachi, S.; Saito, Hidetsugu; Hibi, T.; Maruyama, I.; Kitagawa, Yuukou.

In: European Surgical Research, Vol. 48, No. 3, 06.2012, p. 154-162.

Research output: Contribution to journalArticle

Oshima, G, Shinoda, M, Tanabe, M, Ebinuma, H, Nishiyama, R, Takano, K, Yamada, S, Miyasho, T, Masugi, Y, Matsuda, S, Suda, K, Fukunaga, K, Matsubara, K, Hibi, T, Yagi, H, Hayashida, T, Yamagishi, Y, Obara, H, Itano, O, Takeuchi, H, Kawachi, S, Saito, H, Hibi, T, Maruyama, I & Kitagawa, Y 2012, 'Increased plasma levels of high mobility group box 1 in patients with acute liver failure', European Surgical Research, vol. 48, no. 3, pp. 154-162. https://doi.org/10.1159/000338363
Oshima, Go ; Shinoda, Masahiro ; Tanabe, M. ; Ebinuma, H. ; Nishiyama, R. ; Takano, K. ; Yamada, S. ; Miyasho, T. ; Masugi, Yohei ; Matsuda, Satoru ; Suda, K. ; Fukunaga, Koichi ; Matsubara, Kentaro ; Hibi, T. ; Yagi, Hiroshi ; Hayashida, Tetsu ; Yamagishi, Y. ; Obara, Hideaki ; Itano, O. ; Takeuchi, H. ; Kawachi, S. ; Saito, Hidetsugu ; Hibi, T. ; Maruyama, I. ; Kitagawa, Yuukou. / Increased plasma levels of high mobility group box 1 in patients with acute liver failure. In: European Surgical Research. 2012 ; Vol. 48, No. 3. pp. 154-162.
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T1 - Increased plasma levels of high mobility group box 1 in patients with acute liver failure

AU - Oshima, Go

AU - Shinoda, Masahiro

AU - Tanabe, M.

AU - Ebinuma, H.

AU - Nishiyama, R.

AU - Takano, K.

AU - Yamada, S.

AU - Miyasho, T.

AU - Masugi, Yohei

AU - Matsuda, Satoru

AU - Suda, K.

AU - Fukunaga, Koichi

AU - Matsubara, Kentaro

AU - Hibi, T.

AU - Yagi, Hiroshi

AU - Hayashida, Tetsu

AU - Yamagishi, Y.

AU - Obara, Hideaki

AU - Itano, O.

AU - Takeuchi, H.

AU - Kawachi, S.

AU - Saito, Hidetsugu

AU - Hibi, T.

AU - Maruyama, I.

AU - Kitagawa, Yuukou

PY - 2012/6

Y1 - 2012/6

N2 - 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). Patients and 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. Conclusion: 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.

AB - 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). Patients and 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. Conclusion: 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.

KW - Acute liver failure

KW - Fulminant hepatitis

KW - High-mobility group box 1

KW - Human

KW - Liver transplantation

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