Article Text
Abstract
Objective Hepatitis B surface antigen (HBsAg) loss is the optimal outcome for patients with chronic hepatitis B (CHB) but this rarely occurs with currently approved therapies. We aimed to develop and validate a prognostic model for HBsAg loss on treatment using longitudinal data from a large, prospectively followed, nationwide cohort.
Design CHB patients receiving nucleos(t)ide analogues as antiviral treatment were enrolled from 50 centres in China. Quantitative HBsAg (qHBsAg) testing was prospectively performed biannually per protocol. Longitudinal discriminant analysis algorithm was used to estimate the incidence of HBsAg loss, by integrating clinical data of each patient collected during follow-up.
Results In total, 6792 CHB patients who had initiated antiviral treatment 41.3 (IQR 7.6–107.6) months before enrolment and had median qHBsAg 2.9 (IQR 2.3–3.3) log10IU/mL at entry were analysed. With a median follow-up of 65.6 (IQR 51.5–84.7) months, the 5-year cumulative incidence of HBsAg loss was 2.4%. A prediction model integrating all qHBsAg values of each patient during follow-up, designated GOLDEN model, was developed and validated. The AUCs of GOLDEN model were 0.981 (95% CI 0.974 to 0.987) and 0.979 (95% CI 0.974 to 0.983) in the training and external validation sets, respectively, and were significantly better than those of a single qHBsAg measurement. GOLDEN model identified 8.5%–10.4% of patients with a high probability of HBsAg loss (5-year cumulative incidence: 17.0%–29.1%) and was able to exclude 89.6%–91.5% of patients whose incidence of HBsAg loss is 0. Moreover, the GOLDEN model consistently showed excellent performance among various subgroups.
Conclusion The novel GOLDEN model, based on longitudinal qHBsAg data, accurately predicts HBsAg clearance, provides reliable estimates of functional hepatitis B virus (HBV) cure and may have the potential to stratify different subsets of patients for novel anti-HBV therapies.
- CHRONIC HEPATITIS
- HEPATITIS B
Data availability statement
Data are available on reasonable request. The data that support the findings of this study are available from the corresponding authors on reasonable request.
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Data availability statement
Data are available on reasonable request. The data that support the findings of this study are available from the corresponding authors on reasonable request.
Footnotes
RF and SZ are joint first authors.
Correction notice This article has been corrected since it published Online First. The author affiliation details have been updated.
Collaborators Chronic Hepatitis B Study Consortium for detailed list, please see online supplemental material.
Contributors JH, RF and NVN contributed to the conception and design of the study. JH and RF coordinated the study. RF, JN, HM, QXie, SY, JX, XD, JShang, HR, QXia, YL, YYang, HG, AS, XL, XY, YJ, YYu, JSun and the other members from chronic Hepatitis B Study Consortium (For detailed list, please see online supplemental material) acquired the data. JH, RF and SZ did the statistical analysis, interpreted the data and verified the underlying data. JH, RF, NVN and SZ prepared the manuscript. All authors contributed to the discissions and interpretation of study results, approved the final manuscript and had final responsibility for the decision to submit for publication. JH and RF are the guarantors.
Funding This work was supported by National Key Research and Development Program of China (2022YFC2303600, 2022YFC2304800), the National Natural Science Foundation of China (82170610) and GuangDong Basic and Applied Basic Research Foundation (2023A1515011211).
Competing interests JH received consulting fees from GlaxoSmithKline, Gilead Sciences and a Grant from Roche. NVN is an independent advisor to HistoIndex and a member of the scientific advisory board for InSphero. The other authors declare no conflicts of interest that pertain to this work.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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