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

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...

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Published in:Journal of gastroenterology 2019-06, Vol.54 (6), p.549-557
Main Authors: Kanno, Masataka, Kawaguchi, Kazunori, Honda, Masao, Horii, Rika, Takatori, Hajime, Shimakami, Tetsuro, Kitamura, Kazuya, Arai, Kuniaki, Yamashita, Taro, Sakai, Yoshio, Yamashita, Tatsuya, Mizukoshi, Eishiro, Kaneko, Shuichi
Format: Article
Language:English
Subjects:
Abdominal Surgery
Bile
Biliary Tract
Biopsy
Colorectal Surgery
Complications and side effects
Fatty liver
Fibrosis
Gastroenterology
Hepatocellular carcinoma
Hepatocytes
Hepatology
Hypertension
Liver
Liver cancer
Liver diseases
Medicine
Medicine & Public Health
Original Article—Liver
Pancreas
Prognosis
Protein binding
Reductase
Secretion
Surgical Oncology
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Summary: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.
ISSN:0944-1174
1435-5922
DOI:10.1007/s00535-019-01551-3