Predictors of durable HBsAg loss after pegylated interferon-based therapy in HBeAg-negative CHB patients: a multicenter real-world study

Abstract Background Hepatitis B surface antigen (HBsAg) loss is durable in some chronic hepatitis B (CHB) patients after pegylated interferon alpha (Peg-IFNɑ)-based treatment. However, factors associated with durable HBsAg loss are not clear. This study aimed to investigate predictors of durable HBsAg loss. Methods CHB patients with HBsAg loss were enrolled from 2018 to 2022 in the Everest Project and were followed up for 48 weeks after Peg-IFNɑ therapy discontinuation. Sustained response (SR) was defined as durable HBsAg loss with or without hepatitis B surface antibody (HBsAb) appearance at the end of follow-up (EOF), while recurrence was characterized by HBsAg reversal and/or HBV DNA detectable during follow-up. Data on the risk factors of durable HBsAg loss were analyzed between SR and recurrence. Results 1046 patients were included in this study (822 with SR and 224 with recurrence). 21.41% (224/1046) of patients relapsed at EOF. HBsAb at the end of Peg-IFN treatment (EOT) and Peg-IFN consolidation therapy time were associated with SR (AUROC = 0.709, p < 0.001 and AUROC = 0.620, p < 0.001, respectively), with the optimal cut-off values of 25.67 IU/L and 12.786 weeks, respectively. The prediction model was developed based on HBsAb at EOT and consolidation therapy time, and AUROCs of the model for predicting efficacy in the training and validation sets were 0.7071 and 0.736, respectively. Conclusions HBsAb at EOT and Peg-IFN consolidation therapy time are potential predictors of durable HBsAg loss.