The activation of p38 and NF-κB in Kupffer cells plays an important role in this process because mice with p38α or IKKβ knockout in both hepatocytes and myeloid cells, including Kupffer cells, showed markedly reduced hepatic expression of these cytokines after DEN challenge, resulting in reduced future HCC development [21, 78]. This evidence concerns the gene IKBKB and hepatocellular carcinoma.