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Serum aldo–keto reductase family 1 member B10 predicts advanced liver fibrosis and fatal complications of nonalcoholic steatohepatitis

  • Masataka Kanno
  • Kazunori Kawaguchi
  • Masao HondaEmail author
  • Rika Horii
  • Hajime Takatori
  • Tetsuro Shimakami
  • Kazuya Kitamura
  • Kuniaki Arai
  • Taro Yamashita
  • Yoshio Sakai
  • Tatsuya Yamashita
  • Eishiro Mizukoshi
  • Shuichi Kaneko
Original Article—Liver, Pancreas, and Biliary Tract
  • 48 Downloads

Abstract

Background

Nonalcoholic steatohepatitis (NASH) is associated with liver inflammation in patients with nonalcoholic fatty liver disease, and it can progress to liver fibrosis at an advanced stage, as well as hepatocellular carcinoma (HCC) and portal hypertension. Although liver fibrosis is accurately diagnosed via biopsy, noninvasive methods are preferable. Aldo–keto reductase family 1 member B10 (AKR1B10) is associated with HCC and is secreted into the blood by liver cells via a lysosome-mediated nonclassical pathway. Accordingly, we analyzed whether secretion of AKR1B10 protein is associated with advanced NASH.

Methods

We performed histological staging in 85 Matteoni classification type III and IV NASH patients and evaluated the incidence of HCC, formation of gastroesophageal varices, and prognosis according to serum AKR1B10 and Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA(+)-M2BP)(M2BPGi) and by comparison with conventional markers of fibrosis.

Results

 A positive correlation was found between the Brunt classification and serum AKR1B10 level. In Brunt stage 4 patients, AKR1B10 levels were higher than those of other liver fibrosis markers, with higher specificity. The cutoff values for AKR1B10 and WFA(+)-M2BP for stage 4 fibrosis were 1.03 and 3.11, respectively. The rates of stage 4 fibrosis, HCC incidence, and gastroesophageal varix formation were significantly different between the two groups subdivided according to these cutoff levels. Moreover, the patients in the higher value group had significantly worse prognosis after NASH diagnosis

Conclusion

AKR1B10 is a useful serum biomarker for advanced liver fibrosis in NASH and, combined with serum WFA(+)-M2BP, can predict HCC development, gastroesophageal varix formation, and poor prognosis.

Keywords

Aldo–keto reductase family 1 member B10 Wisteria floribunda agglutinin-positive Mac-2 binding protein Nonalcoholic steatohepatitis 

Notes

Acknowledgements

The authors thank Nami Nishiyama for managing the serum samples.

Compliance with ethical standards

Conflict of interest

The author(s) declare that they have no competing interests.

Supplementary material

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Supplementary material 1 (DOCX 19 kb)
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Supplementary material 3 (TIFF 7358 kb)
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Supplementary material 4 (DOCX 14 kb)

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Copyright information

© Japanese Society of Gastroenterology 2019

Authors and Affiliations

  • Masataka Kanno
    • 1
  • Kazunori Kawaguchi
    • 1
  • Masao Honda
    • 1
    Email author
  • Rika Horii
    • 1
  • Hajime Takatori
    • 1
  • Tetsuro Shimakami
    • 1
  • Kazuya Kitamura
    • 1
  • Kuniaki Arai
    • 1
  • Taro Yamashita
    • 1
  • Yoshio Sakai
    • 1
  • Tatsuya Yamashita
    • 1
  • Eishiro Mizukoshi
    • 1
  • Shuichi Kaneko
    • 1
  1. 1.Department of GastroenterologyKanazawa University Graduate School of Medical ScienceKanazawaJapan

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