Antiviral modulation of immune responses by sex hormones can also help to explain the prevalence of HCC in men, as in the case of chemically induced HCC by diethylnitrosamine (DEN, a chemical carcinogen), which is more severe in males than in female mice, due to an increased production of IL-6 by Kupffer cells (in a manner dependent on the Toll-like receptor adaptor protein MyD88) in the male liver [98]. This evidence concerns the gene TIRAP and hepatocellular carcinoma.