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©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
Serum autotaxin levels are correlated with hepatic fibrosis and ballooning in patients with non-alcoholic fatty liver disease
Naoyuki Fujimori, Takeji Umemura, Takefumi Kimura, Naoki Tanaka, Ayumi Sugiura, Tomoo Yamazaki, Satoru Joshita, Michiharu Komatsu, Yoko Usami, Kenji Sano, Koji Igarashi, Akihiro Matsumoto, Eiji Tanaka
Naoyuki Fujimori, Takeji Umemura, Takefumi Kimura, Ayumi Sugiura, Tomoo Yamazaki, Satoru Joshita, Michiharu Komatsu, Akihiro Matsumoto, Eiji Tanaka, Department of Internal Medicine, Division of Gastroenterology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
Naoki Tanaka, Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, Matsumoto, Japan, and Research Center for Agricultural Food Industry, Shinshu University, Matsumoto, 390-8621, Japan
Yoko Usami, Kenji Sano, Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto 390-8621, Japan
Koji Igarashi, Bioscience Division, TOSOH Corporation, Kanagawa 252-1123, Japan
Author contributions: Umemura T designed the research; Kimura T, Sugiura A, Yamazaki T, Joshita S, Komatsu M and Matsumoto A treated the patients and collected materials and clinical data from patients; Usami Y and Igarashi K performed the assays; Sano K evaluated the histological findings, Fujimori N and Kimura T analyzed the data; Fujimori N, Kimura T and Tanaka N wrote the paper; Tanaka E supervised it.
Institutional review board statement: The study was reviewed and approved by the Committee for Medical Ethics of Shinshu University School of Medicine Institutional Review Board.
Informed consent statement: Written informed consent was obtained from all patients.
Conflict-of-interest statement: The authors declare that no conflict of interest exists.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Takefumi Kimura, MD, PhD, Doctor, Department of Internal Medicine, Division of Gastroenterology, Shinshu University School of Medicine, Asahi 3-1-1, Nagano, Matsumoto 390-8621, Japan.
t_kimura@shinshu-u.ac.jp
Telephone: +81-263-372634 Fax: +81-263-329412
Received: January 17, 2018
Peer-review started: January 17, 2018
First decision: January 25, 2018
Revised: February 10, 2018
Accepted: March 3, 2018
Article in press: March 3, 2018
Published online: March 21, 2018
Processing time: 58 Days and 1.3 Hours
ARTICLE HIGHLIGHTS
Research background
The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. NAFLD exhibits a wide spectrum, ranging from non-alcoholic fatty liver to non-alcoholic steatohepatitis (NASH) and ensuing cirrhosis and hepatocellular carcinoma. Although the evaluation of NAFLD/NASH depends on the histological findings, there is a limitation and an alternative method is required.
Research motivation
Several studies have attempted to estimate histological severity in NAFLD using various serum biomarkers, but the accuracy of these techniques remains unsatisfactory.
Research objectives
Recently, elevated serum autotaxin (ATX) has been implicated in fibrosis progression in chronic liver disease, especially hepatitis C. So, we examine the relationship between serum ATX concentrations and clinicopathological findings in NAFLD patients.
Research methods
One hundred eighty-six NAFLD patients who had undergone liver biopsy between 2008 and 2017 were retrospectively enrolled. Serum samples were collected at the time of biopsy and ATX was measured by enzyme immunoassays. Sera obtained from 160 healthy, non-obese individuals were used as controls. Histological findings were graded according to an NAFLD scoring system and correlations with serum ATX were calculated by Spearman’s test. Diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve (AUC). Cut-off values were identified by the Youden index, and the nearest clinically applicable value to the cutoff was considered the optimal threshold for clinical convenience.
Research results
Serum ATX levels were significantly higher in NAFLD patients than in controls (0.86 vs 0.76 mg/L, P < 0.001) and correlated significantly with ballooning score and fibrosis stage (r = 0.36, P < 0.001 and r = 0.45, P < 0.001, respectively). Such tendencies were stronger in female patients. There were no remarkable relationships between ATX and serum alanine aminotransferase, lipid profiles, or steatosis scores. The AUC values of ATX for predicting the presence of fibrosis (≥ F1), significant fibrosis (≥ F2), severe fibrosis (≥ F3), and cirrhosis (F4), were all more than 0.70 in respective analyses.
Research conclusions
Serum ATX levels may at least partially reflect histological severity in NAFLD.
Research perspectives
In order to evaluate the severity of NAFLD, it is considered that a method that can simultaneously evaluate activity and fibrosis is necessary.
