Genetic insight on non alcoholic fatty liver disease

Abstract

30–32 percent of the total population worldwide suffers from non-alcoholic fatty liver disease (NAFLD). It includes a continuum with conditions such as simple steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. The conventional wisdom has long believed that such lifestyle-related factors as overconsumption of calories, inactive behavior, and insulin resistance are the key perpetrators of its development. Nevertheless, there is mounting evidence that genetic predisposition, epigenetic alterations, and gut microbiome interactions are vital factors that determine the susceptibility, progression, and outcome of this disease. Genetic variations influence the regulation of lipids, inflammation, and fibrosis, while epigenetic modifications impact diet, obesity, and early-life exposures through mechanisms such as DNA methylation, histone modifications, and the actions of non-coding RNAs, often resulting in long-term consequences. Meanwhile, the loss of intestinal barrier integrity in gut microbial dysbiosis exacerbates hepatic disease in a reciprocally reactive relationship with host genetic components. Collective insight from all three disciplines genetics, epigenetics, and microbiome provides healthy insight into the pathophysiology of NAFLD to identify potential opportunities to discover biomarkers, stratified risks, and precision medicine-based interventions. New and promising treatment products, such as targeted dietary supplements, enteric microbiota manipulation, and epigenetic reset, support the possible comparison of primary and individualized interventions to minimize the worldwide NAFLD problem.