The association of PNPLA3 148M with younger age, shorter history of cirrhosis, and less advanced liver disease at HCC diagnosis in ALD&NAFLD is therefore in line with direct carcinogenic activity of PNPLA3 148M, so that 148M homozygotes develop HCC before the other complications of cirrhosis. This evidence concerns the gene PNPLA3 and hepatocellular carcinoma.