Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2015; 21(17): 5138-5148
Published online May 7, 2015. doi: 10.3748/wjg.v21.i17.5138
Reversibility and heritability of liver fibrosis: Implications for research and therapy
Hussein M Atta
Hussein M Atta, Department of Surgery, Faculty of Medicine, Minia University, El-Minia 61519, Egypt
Author contributions: Atta HM solely contributed to this paper.
Supported by Egyptian Science and Technology Development Fund under Project 1550.
Conflict-of-interest: No potential conflicts of interest relevant to this article were reported.
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: Hussein M Atta, MD, PhD, Professor, Department of Surgery, Faculty of Medicine, Minia University, Misr-Aswan Road, El-Minia 61519, Egypt. atta@mu.edu.eg
Telephone: +20-1-001407222 Fax: +20-2-22917077
Received: January 10, 2015
Peer-review started: January 11, 2015
First decision: February 10, 2015
Revised: February 20, 2015
Accepted: March 31, 2015
Article in press: March 31, 2015
Published online: May 7, 2015

Liver fibrosis continues to be a major health problem worldwide due to lack of effective therapy. If the etiology cannot be eliminated, liver fibrosis progresses to cirrhosis and eventually to liver failure or malignancy; both are associated with a fatal outcome. Liver transplantation, the only curative therapy, is still mostly unavailable. Liver fibrosis was shown to be a reversible process; however, complete reversibility remains debatable. Recently, the molecular markers of liver fibrosis were shown to be transmitted across generations. Epigenetic mechanisms including DNA methylation, histone posttranslational modifications and noncoding RNA have emerged as major determinants of gene expression during liver fibrogenesis and carcinogenesis. Furthermore, epigenetic mechanisms have been shown to be transmitted through mitosis and meiosis to daughter cells and subsequent generations. However, the exact epigenetic regulation of complete liver fibrosis resolution and inheritance has not been fully elucidated. This communication will highlight the recent advances in the search for delineating the mechanisms governing resolution of liver fibrosis and the potential for multigenerational and transgenerational transmission of fibrosis markers. The fact that epigenetic changes, unlike genetic mutations, are reversible and can be modulated pharmacologically underscores the unique opportunity to develop effective therapy to completely reverse liver fibrosis, to prevent the development of malignancy and to regulate heritability of fibrosis phenotype.

Keywords: Epigenetics, Epimutations, Inheritance, Liver cirrhosis, Hepatic stellate cells, Histone modification, DNA methylation, MicroRNA, Long noncoding RNA, Transcription regulation

Core tip: Liver fibrosis, if untreated, progresses to cirrhosis and liver failure or malignancy. Liver fibrosis is reversible and potentially heritable process. Heritability and complete reversibility of liver fibrosis although debatable are of profound importance for research and therapy. Epigenetic mechanisms regulate both processes and hold the key for deciphering their regulatory mechanisms and providing new and much needed therapeutic options.