Indeed, in individuals with the most advanced liver disease, there are evidences of selection of somatic variants in Forkhead Box O1 (FOXO1), Cell Death Inducing DFFA Like Effector B (CIDEB) and Glycerol-3-Phosphate Acyltransferase, Mitochondrial (GPAM), involved in the regulation of lipid synthesis and the antioxidant response, leading to a reduction of hepatic fat accumulation possibly accounting for “burnt-out steatohepatitis”, as an adaptive response against chronic lipotoxicity [68, 69]. The gene discussed is FOXO1; the disease is liver disorder.