Genetic association with cirrhosis and HCC among people without viral hepatitis has been reported for the rs738409 C>G single-nucleotide variant (I148M) in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene (OMIM 609567) in chromosome 22.8 The PNPLA3 I148M variant could modulate the outcomes of alcohol intake and obesity, but its interplay with these 2 risk factors in advanced liver disease remains unclear because of the lack of well-powered longitudinal studies.9 This evidence concerns the gene PNPLA3 and hepatocellular carcinoma.