Nucleos(t)ide analogue therapy combined with pegylated interferon α-2b guided by the GOLDEN prediction model for functional cure of chronic hepatitis B: study protocol (GIFT project)
Shiqi Chai, Jingjing Jiang, Chuanna Wang, Yingli He, Xiaoli Jia, Qi Xi, Fuchun Jing, Lijun Chang, Wei Zhang, Ying Guo, Feng Du, Jing Feng, Yuefeng Chai, Yaozhang Cao, Fenxiang Li, Li Zhang, Suling Chen, Yan Wang, Yongmei Lin, Haifang Cao, Yu Zhang, Yunlei Liang, Fangwei Li, Yanqin Hao, Xiaohong Gao, Huaichang Li, Ye Zhang, Wen KangIntroduction
The limited efficacy and tolerability of interferon (IFN)-based therapies make refining patient selection a critical step towards achieving a functional cure in chronic hepatitis B (CHB). The novel GOLDEN model, based on sequential changes in quantitative HBsAg (qHBsAg), accurately predicts hepatitis B surface antigen (HBsAg) loss in patients with CHB receiving nucleos(t)ide analogue (NA) therapy. However, it remains unvalidated in patients receiving sequential pegylated IFN α-2b (Peg-IFN α-2b)-based therapy. We aim to validate the GOLDEN model and the optimised cut-off value for the predictive index (Pi) to prospectively identify optimal candidates for clinical cure among patients receiving sequential Peg-IFN α-2b therapy using pre-IFN treatment qHBsAg kinetics across multiple centres.
Methods and analysis
This prospective multicentre observational cohort study will enrol 300 NA-experienced patients with CHB from 22 centres in China. Patients, stratified by the Pi calculated from pre-treatment qHBsAg dynamics, will be classified into two groups: favourable (Pi>0.15, n=150) and unfavourable candidates (Pi≤0.15, n=150). All patients will receive 48 weeks of combination therapy with Peg-IFN α-2b plus ongoing NAs. The primary endpoint is the HBsAg clearance rate at week 48, with clearance defined as HBsAg loss at any time during the treatment period. Secondary endpoints include HBsAg seroconversion and sustained clearance rates. The sample size provides 80% power to detect a significant difference between the assumed clearance rates (35% vs 20%, favourable vs unfavourable group). Between-group comparisons will be performed using the χ 2 or Fisher’s exact test. Long-term follow-up studies are warranted to assess sustained HBsAg clearance and its impact on clinical outcomes. Concurrently, we will explore establishing novel predictive models using this framework alongside other baseline indicators. Future research could focus on analysing serial inflammatory cytokine profiles from stored blood samples to elucidate the immunological mechanisms driving treatment response.
Ethics and dissemination
The study protocol has been reviewed, and ethical approval has been obtained from the ethics committee of Tangdu Hospital, Fourth Military Medical University (approval no. K202509-69). Approval has also been secured from 21 additional participating centres.
Trial registration number
ChiCTR2500095819.