Histone alteration as epigenetic determinants of metabolic dysfunction associated steatotic liver disease pathogenesis

Abstract

Abstract. Metabolic dysfunction associated steatotic liver disease (MASLD) occupies a prominent position in hepatology and is increasingly recognized as a global epidemic. Accumulating evidence indicates that MASLD represents the hepatic manifestation of a systemic metabolic disorder. The pathogenesis of metabolic diseases is complex and multifactorial, involving the interplay of genetic and epigenetic determinants. Although genetic susceptibility plays a well established role in MASLD pathogenesis, the rapidly increasing prevalence of the disease cannot be adequately explained by genetic predisposition and environmental exposures alone. Epigenetic regulation, encompassing reversible and heritable modifications of gene expression without changes in the underlying nucleotide sequence, constitutes a critical mechanistic link in this context. Growing evidence supports the pivotal role of epigenetic mechanisms in the initiation, progression, and clinical heterogeneity of MASLD.