Epigenetics in inflammatory liver diseases: A clinical perspective (Review)

Abstract

Inflammatory liver diseases are, nowadays, multifactorial and wide-spread, thus having an important socio-economic impact. Although the therapeutic algorithms are well-known in hepatitis, regardless of etiology, strategies to identify inflammatory hepatic lesions in early stages and to develop new epigenetic therapies should be prioritized. The main entities of inflammatory liver disease are: alcoholic and non-alcoholic fatty liver disease, autoimmune hepatitis, viral hepatitis and Wilson disease. The main epigenetic processes include: DNA methylation/demethylation, which imply changes in DNA tertiary structure; post-translational histone covalent changes (methylation/demethylation, acetylation/deacetylation, ubiquitination), that cause DNA-histone instability; synthesis of small, non-coding RNA molecules, called microRNAs, that modulate translational potential of transcripts (mRNAs) and post-translational modification of polypeptide chains. Consequently, the epigenetic interactions aforementioned, play an important modulatory role in disease progression and response to conventional therapies The present review focused on the main epigenetic changes in inflammatory liver conditions, considering a new perspective: Epigenetic therapy. This approach is more than welcomed, taking into consideration that conventional therapeutic strategies are almost exhausted.

Keywords: Wilson disease; acetylation; alcoholic fatty liver disease; autoimmune hepatitis; epigenetics; methylation; microRNA; non-alcoholic fatty liver disease; viral hepatitis.

Figure 1

Cytosine methylation. DNMT, DNA methyltransferases; SAM, S-adenosil-metionine; SAH, S-adenosil-homocysteine.

Figure 2

Histone acetylation and deacetylation.

Figure 3

miRNA regulatory mechanism.