In conclusion, this study demonstrate that increased serum sPD-1 levels are associated with the immune activation and liver inflammation associated with HBV viral replication and the hepatocarcinogenesis in chronic HBV infection, suggesting the involvement of sPD-1 in the disease course of chronic HBV infection and the possibility of using sPD-1 as a biomarker of immune activation and HCC development. The gene discussed is HOXD13; the disease is hepatocellular carcinoma.