Population-based studies have shown that compared to the normal variant homozygosity for this PNPLA3 risk allele is associated with 2 to 4-fold greater risk for NASH and cirrhosis, with up to a 12-fold increased risk for hepatocellular carcinoma and, most recently, an 18-fold increase in liver-related mortality [6, 7]. Here, PNPLA3 is linked to metabolic dysfunction-associated steatohepatitis.