Schofield Z, Reed MA, Newsome PN, Adams DH, Günther UL, Lalor PF. Changes in human hepatic metabolism in steatosis and cirrhosis. World J Gastroenterol 2017; 23(15): 2685-2695 [PMID: 28487605 DOI: 10.3748/wjg.v23.i15.2685]
Corresponding Author of This Article
Dr. Patricia F Lalor, Centre for Liver Research and National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit, Birmingham B152TT, United Kingdom. p.f.lalor@bham.ac.uk
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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/
World J Gastroenterol. Apr 21, 2017; 23(15): 2685-2695 Published online Apr 21, 2017. doi: 10.3748/wjg.v23.i15.2685
Changes in human hepatic metabolism in steatosis and cirrhosis
Zoe Schofield, Michelle AC Reed, Philip N Newsome, David H Adams, Ulrich L Günther, Patricia F Lalor
Zoe Schofield, Sci-Phy-4-Health, EPSRC Research and Training Centre in Physical Sciences for Health, College of Engineering and Physical Sciences, Birmingham B152TT, United Kingdom
Michelle AC Reed, School of Cancer Sciences at the University of Birmingham, Birmingham B152TT, United Kingdom
Philip N Newsome, David H Adams, Patricia F Lalor, Centre for Liver Research and National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit, Birmingham B152TT, United Kingdom
Author contributions: Günther UL and Lalor PF contributed equally to this work, designed the experiments and write the manuscript; Schofield Z performed the experiments and all authors contributed to analysis of data.
Supported bythe National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.
Institutional review board statement: Human liver samples from patients in the Birmingham liver transplantation programme were used throughout this study, and all samples were collected with informed written patient consent and local ethics committee approval (06/Q2702/61).
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
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: Dr. Patricia F Lalor, Centre for Liver Research and National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit, Birmingham B152TT, United Kingdom. p.f.lalor@bham.ac.uk
Telephone: +44-121-4146967 Fax: +44-121-4158701
Received: November 21, 2016 Peer-review started: November 23, 2016 First decision: December 19, 2016 Revised: January 11, 2017 Accepted: March 15, 2017 Article in press: March 15, 2017 Published online: April 21, 2017 Processing time: 149 Days and 18.3 Hours
Abstract
AIM
To understand the underlying metabolic changes in human liver disease we have applied nuclear magnetic resonance (NMR) metabolomics analysis to human liver tissue.
METHODS
We have carried out pilot study using 1H-NMR to derive metabolomic signatures from human liver from patients with steatosis, nonalcoholic steatohepatitis (NASH) or alcohol-related liver damage (ARLD) to identify species that can predict outcome and discriminate between alcohol and metabolic-induced liver injuries.
RESULTS
Changes in branched chain amino acid homeostasis, tricarboxylic acid cycle and purine biosynthesis intermediates along with betaine were associated with the development of cirrhosis in both ARLD and nonalcoholic fatty liver disease. Species such as propylene glycol and as yet unidentified moieties that allowed discrimination between NASH and ARLD samples were also detected using our approach.
CONCLUSION
Our high throughput, non-destructive technique for multiple analyte quantification in human liver specimens has potential for identification of biomarkers with prognostic and diagnostic significance.
Core tip: We have for the first time performed a comparative analysis of 1H-NMR spectra from human liver derived from patients with different, but histologically similar etiologies, and steatotic donor tissue. In agreement with the fibrotic and inflammatory picture in the diseased livers, analytes relating to energy and protein metabolism and ketone body production were altered compared to the donor samples. More importantly, novel combinations of markers that may have diagnostic or prognostic significance were also identified by this approach.
