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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2016; 22(1): 72-88
Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.72
Molecular changes in hepatic metabolism and transport in cirrhosis and their functional importance
Christoph G Dietrich, Oliver Götze, Andreas Geier
Christoph G Dietrich, Bethlehem Center of Health, Department of Internal Medicine, D-52222 Stolberg (Rhineland), Germany
Oliver Götze, Andreas Geier, University of Würzburg, Division of Hepatology, Department of Internal Medicine II, D-97080 Würzburg, Germany
Author contributions: Dietrich CG, Götze O and Geier A researched the literature and wrote the manuscript; all authors approved the final version of the manuscript.
Conflict-of-interest statement: No potential conflict of interest. No financial support.
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: Christoph G Dietrich, MD, PhD, Bethlehem Center of Health, Department of Internal Medicine, Bethlehem-Gesundheitszentrum, Steinfeldstrasse 5, D-52222 Stolberg (Rhineland), Germany.
Telephone: +49-2402-1074223 Fax: +49-2402-1074431
Received: April 29, 2015
Peer-review started: May 8, 2015
First decision: August 25, 2015
Revised: September 24, 2015
Accepted: November 13, 2015
Article in press: November 13, 2015
Published online: January 7, 2016

Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma. The progress of liver fibrosis and cirrhosis is accompanied by deteriorating liver function. This review summarizes the regulatory and functional changes in phase I and phase II metabolic enzymes as well as transport proteins and provides an overview regarding lipid and glucose metabolism in cirrhotic patients. Interestingly, phase I enzymes are generally downregulated transcriptionally, while phase II enzymes are mostly preserved transcriptionally but are reduced in their function. Transport proteins are regulated in a specific way that resembles the molecular changes observed in obstructive cholestasis. Lipid and glucose metabolism are characterized by insulin resistance and catabolism, leading to the disturbance of energy expenditure and wasting. Possible non-invasive tests, especially breath tests, for components of liver metabolism are discussed. The heterogeneity and complexity of changes in hepatic metabolism complicate the assessment of liver function in individual patients. Additionally, studies in humans are rare, and species differences preclude the transferability of data from rodents to humans. In clinical practice, some established global scores or criteria form the basis for the functional evaluation of patients with liver cirrhosis, but difficult treatment decisions such as selection for transplantation or resection require further research regarding the application of existing non-invasive tests and the development of more specific tests.

Keywords: Liver cirrhosis, Drug metabolism, Transport, Breath tests, Lipid metabolism, Glucose metabolism

Core tip: Liver cirrhosis is a common endpoint for many hepatic diseases and is accompanied by the extensive gene regulation of cytokines and enzymes for hepatic metabolism. The resulting organ deficiency complicates treatment decisions, especially regarding transplantation and the resection of hepatocellular carcinoma. This review summarizes the regulatory events involving the metabolism in the cirrhotic liver and puts these events into the context of the non-invasive testing of liver function. This combination can help to better estimate the liver function of individual patients.