These results suggest that elevated sPD-1 level is indicative of the immune activation in chronic HBV infection and the measurement of sPD-1 level may be used as a biomarker of the breaking of immune tolerence in chronic HBV infection which is an important reference for the initiation of treatment using either interferon or nucleos(t)ide analogues [6] and a potential rationale for the design of cancer immunotherapy [38]. Here, HOXD13 is linked to cancer.