BecauseRIG-1 and MDA5 are the innate immune receptors that recognize microbial PAMPs andthen activate downstream molecules, including IPS-1 and RIP1, which consequentlyresult in activation of pro-inflammatory transcription factors such as IRF3 and IRF7(Reikine et al., 2014;Li et al., 2018), itseems that RIG-1/MDA5 and its downstream molecules can be considered as unknownparts of the CHB-related liver cirrhosis and HCC puzzle. Here, IRF3 is linked to hepatocellular carcinoma.