Epigenetic basis for environmentally induced liver disease

The liver, which is central to detoxification and metabolism, interacts with growing threats from environmental exposures that alter epigenetic mechanisms and contributes to the development of liver disease. Dietary contaminants, industrial chemicals, and lifestyle factors induce aberrant DNA methylation, histone modifications, and epitranscriptomic shifts that create persistent cellular memories. These epigenetic alterations may be inherited via germline transmission, disrupting hepatic gene networks across generations. Addressing environmentally induced liver disease requires a systems-level approach that takes into account interconnected epigenetic pathways rather than a reductionist approach of targeted gene/promoter-based analyses. This review discusses mechanisms related to how environmental cues induce liver disease development, the shifts in biological pathways linked to liver pathology, the role of the environmentally established epigenetic landscape in liver disease progression, and possible methods for the mitigation of environmentally induced liver disease, particularly nonalcoholic fatty liver disease (also called metabolic dysfunction-associated steatotic liver disease (MASLD)), since this disease has no FDA-approved drug for treatment.