PNPLA3 and metabolic dysfunction-associated steatohepatitis: These include the Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M gene variant, which has been demonstrated to represent a major determinant of interindividual and ethnicity-related differences in hepatic fat content independent of IR and serum lipid concentration, and a determinant of the progression towards NASH and fibrosis [19, 20].