High levels of soluble programmed death-1 are associated with virological response in chronic hepatitis B patients after antiviral treatment

Soluble programmed cell death protein-1 (sPD-1) plays an important role in chronic hepatitis B virus (HBV) infection by counteracting the inhibitory effect of programmed death ligand-1 (PD-L1) on immune cells. Here, we investigated the ability of sPD-1 to predict the virological response (VR) in chronic hepatitis B (CHB) patients undergoing Nucleos(t)ide analogue (NA) therapy.

By combining sPD-1 and HBsAg, we obtained a biomarker significantly associated with VR in CHB patients. The sPD-1 levels could be used to screen out patients with poor prognosis of antiviral therapy.

CHB patients [hepatitis B surface antigen (HBsAg) positive ≥6 months] who initiated NA therapy in March 2007 at Peking University First Hospital (China) were enrolled in this study. Eighty-nine CHB patients were followed-up every 12 weeks for 96 weeks.

Serum sPD-1 levels at baseline were negatively correlated with hepatitis B surface antigen (HBsAg) and HBV DNA. Immune-active CHB patients exhibited higher serum sPD-1 levels at baseline. Patients with VR during the antiviral treatment exhibited higher sPD-1 levels and lower HBsAg levels at baseline. Receiver operating characteristic (ROC) curves were generated to determine the predictive value of sPD-1 and HBsAg for VR in patients who received first-line therapy (entecavir, ETV). The area under ROC (AUROC) values of sPD-1 and HBsAg at baseline were 0.850 (95%CI:0.729-0.971, P = 0.0005) and 0.785 (95%CI: 0.642-0.929, P = 0.005), respectively, and the optimal cut-off values were 459.46 pg/mL and 14,710 IU/mL, respectively. The combination of sPD-1 and HBsAg exhibited a higher AUROC value (0.870,95% CI: 0.748-0.983, P = 0.001) than did sPD-1 or HBsAg alone. In patients administered second-line therapy (lamivudine, LAM/adefovir divipoxil, ADV), baseline sPD-1 levels above 677.2 pg/mL were significantly associated with higher incidence of VR after 96 weeks of antiviral therapy. It is 7.956 times the level of ≤677.2 pg/mL. Conclusions: By combining sPD-1 and HBsAg, we obtained a biomarker significantly associated with VR in CHB patients. The sPD-1 levels could be used to screen out patients with poor prognosis of antiviral therapy.