Epigenetics in liver disease
Open accessAbstract
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)
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The multiple hits theory is supported by rodent models of MASH characterised by excess calorie intake, weight gain and onset of insulin resistance in which increased hepatic lipid accumulation is observed, but additional insults are required to initiate inflammation and fibrosis.
“The 'multiple hits' theory is supported by rodent models of MASH characterised by excess calorie intake, weight gain and the onset of IR in which increased hepatic lipid accumulation is observed, but additional insults are required to initiate inflammation and fibrosis.”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [225]
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Experimental — accuracy not yet measuredAdditional insults in MASH include altered gut flora and increased intestinal permeability, circadian rhythm misalignment, epigenetic modifications, and changes to the composition of liver myeloid cell populations.
“These include altered gut flora and an increase in intestinal permeability(222, 223), circadian rhythm misalignment(224), epigenetic modifications(210, 225) and changes to the composition of liver myeloid cell populations(210, 211, 226).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [225]
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- Authors
- Mann, D. A.
- Affiliations
- Newcastle University (GB)
- Corresponding author
- Mann, Derek A.
- ORCID
- Mann, Derek A.
- Venue
- Hepatology
- Published
- 2014-10
- Volume
- 60
- Issue
- 4
- Pages
- 1418-1425
- ISSN
- 0270-9139 (ISSN-L)
- PMC
- PMC4258082
- OpenAlex
- W2000252175
- Cited by
- 153
- References
- 64
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 13 · 2023: 5 · 2022: 11 · 2021: 7 · 2020: 11 · 2019: 11 · 2018: 18 · 2017: 16 · 2016: 17 · 2015: 24 · 2014: 3
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Hepatology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- Medical Research Council (MR/K001949/1)
- National Institute on Alcohol Abuse and Alcoholism (U01AA018663)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- epigenetics, liver disease, DNA methylation, histone modifications, chromatin remodeling, transcriptional regulation, non-coding RNA, liver cancer, liver fibrosis, nonalcoholic steatohepatitis, epigenetic therapy, epigenetic inheritance, epigenetic profiling
- MeSH terms
- Chromatin, Histones, Humans, Liver Diseases, Transcription, Genetic, DNA Methylation, Disease Management, RNA, Untranslated, Epigenomics
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