Predictors of Durable Hepatitis B Surface Antigen Loss After Pegylated Interferon–Based Therapy in Patients with Hepatitis B e Antigen–Negative Chronic Hepatitis B: A Multicenter Real-World Study

BACKGROUND: Hepatitis B surface antigen (HBsAg) loss is durable in some patients with chronic hepatitis B (CHB) after pegylated interferon α (Peg-IFNα)-based treatment. However, factors associated with durable HBsAg loss are not clear. This study aimed to investigate predictors of durable HBsAg loss. METHODS: Patients with CHB and HBsAg loss were enrolled from 2018 to 2022 in the Everest Project and followed up for 48 weeks after Peg-IFNα 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, while recurrence was characterized by HBsAg reversal and/or detectable HBV DNA during follow-up. Data on the risk factors of durable HBsAg loss were analyzed between SR and recurrence. RESULTS: A total of 1046 patients were included in this study: 822 with SR and 224 with recurrence. At end of follow-up, 1.41% (224/1046) had relapsed. HBsAb at the end of Peg-IFNα treatment and Peg-IFNα consolidation therapy time were associated with SR (area under the receiver operating curve [AUROC], 0.709 [P < .001]; AUROC, 0.620 [P < .001], respectively), with the optimal cutoff values of 25.67 IU/L and 12.786 weeks. The prediction model was based on HBsAb at end of treatment and consolidation therapy time, and AUROCs of the model for predicting efficacy in the training and validation sets were 0.7071 and 0.736. CONCLUSIONS: HBsAb at end of treatment and Peg-IFNα consolidation therapy time are potential predictors of durable HBsAg loss.