Ever since the discovery that a substantial proportion of patients with CHC have a strong induction of hundreds of ISGs in the liver (Chen et al, 2005; Asselah et al, 2008; Sarasin‐Filipowicz et al, 2008) it remained unclear why the endogenous IFN system is ineffective against HCV, whereas therapies with recombinant (pegylated) IFN‐α were curative in many patients. Here, IFNA1 is linked to cryohydrocytosis.