Objective:The programmed death receptor 1/programmed death ligand 1 (PD-1/PD-L1) pathway can negatively regulate the immune response of the body, and serum soluble PD-L1 (sPD-L1) can reflect the expression level of PD-L1. This study aims to compare the expressional differences of sPD-L1 in serum between patients with chronic hepatitis B (CHB) and C (CHC) and further explore the factors influencing the clinical cure of CHB.Methods:60 cases with CHB, 40 cases with CHC, and 60 healthy controls were selected. Serum levels of sPD-L1 were detected using an ELISA kit. The relationship between sPD-L1 levels and viral load, liver injury indicators, and others was analyzed in CHB and CHC patients. According to the distribution type of the data, a one-way ANOVA or Kruskal Wallis test as well as Pearson’s correlation or Spearman’s rank correlation analysis were performed. A difference of P<0.05 was considered statistically significant.Results:The serum sPD-L1 levels were significantly higher in CHB patients (414.6 ± 214.9) pg/ml than those in CHC patients (58.9 ± 122.1) pg/ml and the healthy control group (66.27 ± 24.43) pg/ml, and there was no statistically significant difference in serum sPD-L1 between CHC patients and the healthy control group. Further grouping and correlation analysis showed that the level of serum sPD-L1 was positively correlated with the content of HBsAg in CHB patients but not with HBV DNA, alanine transaminase, albumin, and other liver injury indicators. Additionally, there was no correlation between serum sPD-L1 levels, HCV RNA, and liver injury indicators in CHC patients.Conclusion:The serum sPD-L1 levels are significantly higher in CHB patients than those in the healthy control group and the CHC group, and there is a positive correlation between sPD-L1 levels and HBsAg. The persistent presence of HBsAg is an important mechanism for the activity of the PD-1/PD-L1 pathway, indicating that the activity of the PD-1/PD-L1 pathway may be an important factor that cannot be clinically cured in CHB as in CHC.