Observational Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2017; 23(4): 712-722
Published online Jan 28, 2017. doi: 10.3748/wjg.v23.i4.712
Association between endotoxemia and histological features of nonalcoholic fatty liver disease
Hiroyuki Kitabatake, Naoki Tanaka, Naoyuki Fujimori, Michiharu Komatsu, Ayaka Okubo, Kyogo Kakegawa, Takefumi Kimura, Ayumi Sugiura, Tomoo Yamazaki, Soichiro Shibata, Yuki Ichikawa, Satoru Joshita, Takeji Umemura, Akihiro Matsumoto, Masayoshi Koinuma, Kenji Sano, Toshifumi Aoyama, Eiji Tanaka
Hiroyuki Kitabatake, Naoki Tanaka, Toshifumi Aoyama, Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan
Hiroyuki Kitabatake, Naoyuki Fujimori, Michiharu Komatsu, Ayaka Okubo, Kyogo Kakegawa, Takefumi Kimura, Ayumi Sugiura, Tomoo Yamazaki, Soichiro Shibata, Yuki Ichikawa, Satoru Joshita, Takeji Umemura, Akihiro Matsumoto, Eiji Tanaka, Department of Internal Medicine, Division of Gastroenterology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
Masayoshi Koinuma, Center for Clinical Research, Shinshu University Hospital, Matsumoto 390-8621, Japan
Masayoshi Koinuma, Faculity of Pharmaceutical Sciences, Teikyo Heisei University, Tokyo 164-8530, Japan
Kenji Sano, Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto 390-8621, Japan
Author contributions: Tanaka N designed research; Kitabatake H, Tanaka N, Okubo A, Kakegawa K and Sano K performed research; Kitabatake H, Tanaka N, Fujimori N and Koinuma M analyzed data; Tanaka N, Fujimori N, Komatsu M, Kimura T, Sugiura A, Yamazaki T, Shibata S, Ichikawa Y, Joshita S, Umemura T and Matsumoto A collected data; Kitabatake H and Tanaka N wrote the manuscript; Aoyama T and Tanaka E supervised the manuscript.
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: Informed written consent was obtained from all patients.
Conflict-of-interest statement: The authors declare that no conflicts of interest exist.
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: Naoki Tanaka, MD, PhD, Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan. naopi@shinshu-u.ac.jp
Telephone: +81-263-372634 Fax: +81-263-329412
Received: September 13, 2016
Peer-review started: September 16, 2016
First decision: September 20, 2016
Revised: November 14, 2016
Accepted: January 2, 2017
Article in press: January 3, 2017
Published online: January 28, 2017
Processing time: 127 Days and 21.8 Hours
Abstract
AIM

To assess whether surrogate biomarkers of endotoxemia were correlated with the histological features of nonalcoholic fatty liver disease (NAFLD).

METHODS

One hundred twenty-six NAFLD patients who had undergone percutaneous liver biopsy were enrolled. Serum lipopolysaccharide (LPS)-binding protein (LBP) and anti-endotoxin core immunoglobulin G (EndoCab IgG) antibody concentrations at the time of liver biopsy were measured using the enzyme-linked immunosorbent assays to examine for relationships between biomarker levels and histological scores.

RESULTS

Serum LBP concentration was significantly increased in nonalcoholic steatohepatitis (NASH) patients as compared with nonalcoholic fatty liver (NAFL) subjects and was correlated with steatosis (r = 0.38, P < 0.0001) and ballooning scores (r = 0.23, P = 0.01), but not with the severity of lobular inflammation or fibrosis. Multivariate linear regression analysis revealed that LBP was associated with steatosis score and circulating C-reactive protein, aspartate aminotransferase, and fibrinogen levels. Serum EndoCab IgG concentration was comparable between NASH and NAFL patients. No meaningful correlations were detected between EndoCab IgG and histological findings.

CONCLUSION

LBP/EndoCab IgG were not correlated with lobular inflammation or fibrosis. More accurate LPS biomarkers are required to stringently assess the contribution of endotoxemia to conventional NASH.

Keywords: Nonalcoholic steatohepatitis; Endotoxemia; Lipopolysaccharide-binding protein; EndoCab IgG; Fibrosis; Steatosis

Core tip: This is the first study simultaneously measuring two surrogate endotoxemia markers, lipopolysaccharide-binding protein (LBP) and EndoCab IgG, in biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients in order to assess for relationships with the histological features of NAFLD. Serum LBP/EndoCab IgG were not correlated with lobular inflammation or fibrosis. It remains elusive whether portal endotoxemia promotes hepatitis/fibrosis in human conventional NAFLD/nonalcoholic steatohepatitis.