In search of intrahepatic ISGs associated with immune clearance of HBV, a growing body of evidence implies that ISG20 may be involved in IFN mediated inhibition of HBV, including 1) the upregulation of ISG20 in HBV transgenic mouse hepatocyte cell lines in which the HBV replication was inhibited by IFN [19]; 2) the elevation of ISG20 level in viral clearance phase of an acutely HBV infected Chimpanzee [35]; and 3) the upregulation of ISG20 in chronic hepatitis B patients who responded well to IFN-α therapy [21]. The gene discussed is ISG20; the disease is chronic hepatitis B virus infection.