Prediction of hepatocellular carcinoma development by plasma ADAMTS13 in chronic hepatitis B and C.

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http://cebp.aacrjournals.org/content/early/2011/08/26/1055-9965.EPI-11-0464.abst\

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Prediction of hepatocellular carcinoma development by plasma ADAMTS13 in chronic

hepatitis B and C.

Hitoshi Ikeda1,*,

Ryosuke Tateishi2,

Kenichiro Enooku3,

Haruhiko Yoshida2,

Hayato Nakagawa4,

Ryota Masuzaki5,

Yuji Kondo6,

Tadashi Goto6,

Shuichiro Shiina7,

Yukio Kume8,

Tomoaki Tomiya2,

Yukiko Inoue6,

Takako Nishikawa6,

Natsuko Ohtomo7,

Yasushi Tanoue7,

Tomoko Ono9,

Kazuhiko Koike10, and

Yutaka Yatomi8

+ Author Affiliations

1Department of Clinical Laboratory Medicine, The University of Tokyo

2Department of Gastroenterology, The University of Tokyo

3Department of Gastroenterology, Graduate School of Medicine, the University of

Tokyo

4Department of Gastroenterology, University of Tokyo

5University of Tokyo

6The University of Tokyo

7Gastroenterology, University of Tokyo

8Department of Laboratory Medicine, The University of Tokyo

9Mitsubishi Chemical Medicine Corporation

10Department of Gatroenterology, The University of Tokyo

↵*Corresponding Author:

Hitoshi Ikeda, Department of Clinical Laboratory Medicine, The University of

Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan ikeda-1im@...

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

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 AST and ALT, 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, HCC 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. Impact:Plasma

ADAMTS13 as a potential marker of hepatic stellate cells may be useful in the

prediction of hepatocarcinogenesis.

Received May 18, 2011.

Revision received August 19, 2011.

Accepted August 20, 2011.

Copyright © 2011, American Association for Cancer Research.