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. The gene discussed is PNPLA3; the disease is Cirrhosis.