High Level of Soluble Programmed Death-1 Is Associated with Functional Cure in Chronic Hepatitis B Upon Long-Term Treatment

Background & Aims: Some studies showed that soluble forms of programmed death1(sPD-1) could interact with programmed death ligand-1 (PD-L1) expressed on the membrane and counteract its inhibitory influence on immune cells. This study aimed to investigate the predictive value of sPD-1 in chronic hepatitis B (CHB) for functional cure during Nucleos(t)ide analogues (NAs) therapy. Methods: Eighty-four CHB patients were enrolled and started antiviral treatment in March 2007 at the Department of Infectious Diseases at Peking University First Hospital in Beijing. Findings: After 10 years of follow-up, 44 patients achieved low hepatitis B surface antigen(HBsAg) levels. The results indicated that a baseline sPD-1 level ≥500 pg/mL was associated with a higher incidence of low HBsAg levels (n=30/34, 88.2% at year 10) compared with a level <500 pg/mL (n=14/29, 48.3% at year 10) (HR 2.94; P<0.001). Moreover, sPD-1≥500 pg/mL at baseline (OR 17.33; P=0.001) and age (OR 1.11; P=0.031) could predict low HBsAg levels after 10-year follow-up. Interpretation: Baseline sPD-1≥500 pg/mL could predict low HBsAg levels and was associated with a higher incidence of low HBsAg levels after the 10-year follow-up. High serum sPD-1 levels and age might be used to distinguish patients with a higher incidence of a functional cure. Funding Statement: The 13th Five-Year Plan, No.2018ZX09206005-002，Ministry of Science and Technology of the People’s Republic of China. Declaration of Interests: There are no conflicts of interest to report. Ethical Approval Statement: The study was approved by the Institutional Review Board of the Peking University First Hospital. The study protocol conformed to the ethical guidelines of the Declaration of Helsinki and was approved by the Ethics Committee of Shanghai Jing An Central Hospital (Approval no. 090f51e6809a26e1 v1.0).