Importantly, studies reporting an increased incidence of HCC in CHC patients who are homozygous for the PNPLA3 rs738409 G-allele, suggesting a cancerogenic effect of this variant—possibly due to increases in hepatic inflammation [18]—were mostly performed prior to the availability of IFN-free therapies [42]. Here, PNPLA3 is linked to cryohydrocytosis.