Fourth, considering that ERα gene polymorphism is associated with risk of HBV-related acute liver failure [113] and a switch from the authentic ERα to a predominant expression of ERα36 is associated with development and progression of HCC [114–116], the hepatic ERα variants could also play an important role in alcohol and ER stress-associated HCC. This evidence concerns the gene ESR1 and hepatocellular carcinoma.