Epigenetic changes and their implications in autoimmune hepatitis

Abstract

Background: The genetic risk of autoimmune hepatitis is insufficient to explain the observed risk, and epigenetic changes may explain disparities in disease occurrence in different populations within and between countries. The goal of this review was to examine how epigenetic changes induced by the environment or inherited as a phenotypic trait may affect autoimmune hepatitis and be amenable to therapeutic intervention. Materials and methods: Pertinent abstracts were identified in PubMed by multiple search terms. The number of abstracts reviewed was 1689, and the number of full-length articles reviewed exceeded 150. Results: Activation of pro-inflammatory genes in autoimmune disease is associated with hypomethylation of deoxyribonucleic acid and modification of histones within chromatin. Organ-specific microribonucleic acids can silence genes by marking messenger ribonucleic acids for degradation, and they can promote inflammatory activity or immunosuppression. High circulating levels of the microribonucleic acids 21 and 122 have been demonstrated in autoimmune hepatitis, and they may increase production of pro-inflammatory cytokines. Microribonucleic acids are also essential for maintaining regulatory T cells. Drugs, pollutants, infections, diet and ageing can induce inheritable epigenetic changes favouring autoimmunity. Reversal is feasible by manipulating enzymes, transcription factors, gene-silencing molecules and toxic exposures or by administering methyl donors and correcting vitamin D deficiency. Gene targets, site specificity, efficacy and consequences are uncertain. Conclusions: Potentially reversible epigenetic changes may affect the occurrence and outcome of autoimmune hepatitis, and investigations are warranted to determine the nature of these changes, key genomic targets, and feasible interventions and their consequences.

Review article: iron disturbances in chronic liver diseases other than haemochromatosis – pathogenic, prognostic, and therapeutic implications

“…The pathogenic basis for the iron dysregulation in chronic liver diseases other than hereditary haemochromatosis is unclear, but it may relate to genetic ( HFE and non‐ HFE genes), epigenetic (toxins, nutrition), and disease‐related (cytokine responses, tissue hypoxia, hepatocyte damage) factors that disrupt iron homeostasis. The serum hepcidin response to the liver injury may be the pivotal factor in understanding the basis for the iron disturbance and directing management.…”

Pathophysiological Role and Therapeutic Implications of Vitamin D in Autoimmunity: Focus on Chronic Autoimmune Diseases

“…Kempinska-Podhorodecka et al found that in PBC livers, either cirrhotic or not, there is a significant impairment in VDR expression, resulting in enhancement of non-coding miR155 and consequent SOCS1 reduction, which probably interferes with the negative feedback on pro-inflammatory cytokines response [275]. Actually, VDR is also an important receptor for ursodeoxycholic acid (UDCA) inducing cathelicidin expression in biliary epithelial cells [243]; it also mediates many epigenetic effects, which contribute to the reduction of pro-inflammatory cytokines synthesis [276].…”

Epigenetics of gastrointestinal diseases: notes from a workshop

“…Genetic mutations have been identified as causing or enhancing susceptibility for each of these diseases; however, such mutations are observed in the minority of patients, suggesting that alternative factors regulate disease incidence. In addition, these diseases have highly variable presentation between patients, and this variability is not fully explained by inherited genetic factors [1–10]. Thus, aspects of these diseases are likely to be regulated by epigenetic mechanisms.…”