Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 18, 2017; 9(8): 443-454
Published online Mar 18, 2017. doi: 10.4254/wjh.v9.i8.443
Meta-analysis reveals up-regulation of cholesterol processes in non-alcoholic and down-regulation in alcoholic fatty liver disease
Wasco Wruck, James Adjaye
Wasco Wruck, James Adjaye, Medical Faculty, Institute for Stem Cell Research and Regenerative Medicine, Heinrich Heine University, 40225 Düsseldorf, Germany
Author contributions: Wruck W performed transcriptomics analyses and the meta-analysis; Wruck W and Adjaye J wrote the manuscript; Adjaye J initiated and co-ordinated the work.
Supported by The Medical Faculty of the Heinrich Heine University Düsseldorf.
Conflict-of-interest statement: The authors have no conflict of interest.
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:
Correspondence to: James Adjaye, PhD, Professor, Medical Faculty, Institute for Stem Cell Research and Regenerative Medicine, Heinrich Heine University, Moorenstrasse 5, 40225 Düsseldorf, Germany.
Telephone: +49-0211-8108191 Fax: +49-0211-8117858
Received: October 12, 2016
Peer-review started: October 17, 2016
First decision: November 14, 2016
Revised: November 29, 2016
Accepted: December 13, 2016
Article in press: December 14, 2016
Published online: March 18, 2017

To compare transcriptomes of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) in a meta-analysis of liver biopsies.


Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD.


We observed predominating commonalities at the transcriptome level between ALD and NAFLD, most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction, phagosome and lysosome. However some pathways were regulated in opposite directions in ALD and NAFLD, for example, glycolysis was down-regulated in ALD and up-regulated in NAFLD. Interestingly, we found rate-limiting genes such as HMGCR, SQLE and CYP7A1 which are associated with cholesterol processes adversely regulated between ALD (down-regulated) and NAFLD (up-regulated). We propose that similar phenotypes in both diseases may be due to a lower level of the enzyme CYP7A1 compared to the cholesterol synthesis enzymes HMGCR and SQLE. Additionally, we provide a compendium of comparative KEGG pathways regulation in ALD and NAFLD.


Our finding of adversely regulated cholesterol processes in ALD and NAFLD draws the focus to regulation of cholesterol secretion into bile. Thus, it will be interesting to further investigate CYP7A1-mediated cholesterol secretion into bile - also as possible drug targets. The list of potential novel biomarkers may assist differential diagnosis of ALD and NAFLD.

Keywords: Non-alcoholic fatty liver disease, Alcoholic liver disease cholesterol, Bile, Alcohol dehydrogenase, CYP7A1

Core tip: With a meta-analysis of newly published liver biopsy-derived transcriptome datasets we identified multiple key genes and pathways in common and mutually exclusive in alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). We provide a compendium of comparative regulation for all KEGG pathways in both diseases and propose a list of biomarkers distinguishing both diseases. One surprising finding was that cholesterol metabolism was up-regulated in NAFLD and down-regulated in ALD although leading to the same steatosis phenotype which might be explained by an insufficient conversion rate to bile acids under both conditions.