Epigenetics in liver disease

Abstract

Epigenetics is a term that encompasses a variety of regulatory processes that are able to crosstalk in order to influence gene expression and cell phenotype in response to environmental cues. A deep understanding of epigenetics offers the potential for fresh insights into the basis for complex chronic diseases and improved diagnostic and prognostic tools. Moreover, as epigenetic modifications are highly plastic and responsive to the environment, there is much excitement around the theme of epigenetic therapeutics, including not only new drugs but also more informed patient advice on lifestyle choices and their impact on pathology. This review briefly explains the molecular nature of the individual regulatory process that constitute epigenetics, including DNA methylation, histone modifications, chromatin remodeling, transcriptional control, and noncoding RNAs. The ways in which these epigenetic mechanisms influence liver physiology and disease will be considered in detail, particularly in the context of cancer, fibrosis, and nonalcoholic steatohepatitis. The current limitations associated with epigenetic profiling and therapeutics in liver disease are discussed, as is the intriguing possibility that environmental-induced epigenetic changes may become stable and heritable. Conclusion: The aim of the review is to inform hepatologists of the emerging key epigenetic ideas of relevance to liver diseases that are highly likely to form a component of patient management and care in the next decade. (Hepatology 2014;60:1418–1425)

Pathobiology of liver fibrosis: a translational success story

“…Epigenetic regulation is an especially important mode of controlling stellate cell activation, because regulatory events must occur quickly following injurious stimuli, either by activating or repressing gene transcription, or by post-transcriptional control 37 (see figure 3). Among epigenetic signals, microRNAs are an important layer of regulatory control in stellate cell activation and fibrosis.…”

To die or not to die: death signaling in nonalcoholic fatty liver disease

“…They include DNA methylation, altered expression of non-coding RNAs, histone modification, and chromatin remodeling [102, 103]. Epigenetic changes can be reversed by interventional approaches [104], raising clinical interest in this area [105–107]. This chapter will mainly focus on non-coding RNAs, the most intensively investigated form of epigenetic machinery and the one most related to hepatocyte death signaling [108].…”

Hepatic DNA Methylation Is Affected by Hepatocellular Carcinoma Risk in Patients with and without Hepatitis Virus

“…In the virus-related HCC group, liver fibrosis was more prominent in HCV- than in HBV-positive patients; this might lead to methylation status differences of DM-CpGs between cirrhotic and non-cirrhotic livers [28]. Alternatively, the duration of hepatitis, which should be related fibrosis progression, could affect DM-CpG loci methylation within the background liver.…”