Serum sPD‐1 and sPD‐L1 as predictive biomarkers for HBsAg clearance in HBeAg‐negative CHB patients undergoing IFN‐based therapy

Summary Background and Aims For chronic hepatitis B (CHB) patients, there is still a need to improve hepatitis B surface antigen (HBsAg) clearance rates. This study aimed to assess the predictive effectiveness of soluble programmed cell death‐1 (sPD‐1) and soluble programmed cell death ligand‐1 (sPD‐L1) for HBsAg clearance in HBeAg‐negative CHB patients undergoing peginterferon (Peg‐IFN)‐based antiviral treatment. Methods This study encompassed 280 patients undergoing treatment with Peg‐IFNα. Serum levels of sPD‐1 and sPD‐L1 were measured using ELISA kits at baseline, as well as at 12, 24 and 48 weeks. The primary endpoint of the study was the determination of HBsAg clearance at 48 weeks. Logistic regression analysis was employed to identify predictors of HBsAg clearance. Results The clearance group demonstrated significantly lower serum sPD‐L1 levels compared to the non‐clearance group. While both groups exhibited an increase in sPD‐1 levels, only the clearance group showed a rise in sPD‐L1 levels. Multivariate analysis identified sPD‐L1 increase at 24 weeks, and HBsAg decline at 24 weeks as predictors for HBsAg clearance at 48 weeks. The combined use of these indicators showed a predictive performance for HBsAg clearance with an AUROC of 0.907 (95% CI: 0.861–0.953, p < 0.001). Conclusions The study revealed an inverse relationship between the trends of sPD‐1/sPD‐L1 and HBsAg clearance during combined IFN and NAs treatment. Moreover, the magnitude of HBsAg reduction and sPD‐L1 increase emerged as significant predictors for HBsAg clearance.