Interferon-based HBV function cure therapy reduces hepatocellular carcinoma risk in low-HBsAg chronic hepatitis B patients: a propensity-matched cohort study and dynamic prediction model
- 1Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University
- 2Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University
- 3The Second School of Clinical Medicine, Southern Medical University
Abstract
Background: Functional cure through HBsAg loss is a key treatment goal in chronic hepatitis B (CHB), yet its impact on hepatocellular carcinoma (HCC) risk remains incompletely characterized, especially when achieved via interferon (IFN)-based therapy. We aimed to evaluate the HCC risk reduction associated with IFN-based therapy in low-HBsAg CHB patients and develop a validated prediction model for this population.
Methods: We conducted a retrospective cohort study of 3,367 CHB patients with HBsAg <1,500 IU/mL, including 1,780 receiving IFN-based therapy and 1,587 on nucleos(t)ide analogue (NAs) monotherapy. Propensity score matching (PSM) was used to balance baseline characteristics. Cox regression and time-dependent ROC analyses were employed to develop a dynamic nomogram for HCC prediction.
Results: IFN-based therapy was associated with a significantly lower HCC incidence compared to NAs monotherapy (1.2% vs. 4.9%, p<0.001), with a hazard ratio of 3.03 (95% CI: 1.82–5.06) after PSM. The protective effect was most pronounced in cirrhotic patients (absolute risk reduction 8.8%, NNT = 11). A novel nomogram incorporating treatment modality, AFP, cirrhosis, age, and other variables demonstrated excellent predictive accuracy (5-year AUC: 0.888 in derivation, 0.956 in validation cohorts), outperforming existing HCC prediction models.
Conclusions: IFN-based therapy significantly reduces HCC risk in low-HBsAg CHB patients, particularly those with cirrhosis. We developed and validated a dynamic prediction model that may facilitate personalized surveillance and treatment decisions in functionally cured patients.
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BibTeX
@article{gu2026interferonbased,
title = {{Interferon-based HBV function cure therapy reduces hepatocellular carcinoma risk in low-HBsAg chronic hepatitis B patients: a propensity-matched cohort study and dynamic prediction model}},
author = {Yurong Gu and Peipei Wang and Qinyao Xu and Ting Liu and Huaping Xie and Baoer Wu and Yusheng Jie and Xiangyong Li},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1955742},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1955742/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Interferon-based HBV function cure therapy reduces hepatocellular carcinoma risk in low-HBsAg chronic hepatitis B patients: a propensity-matched cohort study and dynamic prediction model
AU - Yurong Gu
AU - Peipei Wang
AU - Qinyao Xu
AU - Ting Liu
AU - Huaping Xie
AU - Baoer Wu
AU - Yusheng Jie
AU - Xiangyong Li
PY - 2026
DA - 2026/10/19
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1955742
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1955742/full
AB - Background: Functional cure through HBsAg loss is a key treatment goal in chronic hepatitis B (CHB), yet its impact on hepatocellular carcinoma (HCC) risk remains incompletely characterized, especially when achieved via interferon (IFN)-based therapy. We aimed to evaluate the HCC risk reduction associated with IFN-based therapy in low-HBsAg CHB patients and develop a validated prediction model for this population. Methods: We conducted a retrospective cohort study of 3,367 CHB patients with HBsAg <1,500 IU/mL, including 1,780 receiving IFN-based therapy and 1,587 on nucleos(t)ide analogue (NAs) monotherapy. Propensity score matching (PSM) was used to balance baseline characteristics. Cox regression and time-dependent ROC analyses were employed to develop a dynamic nomogram for HCC prediction. Results: IFN-based therapy was associated with a significantly lower HCC incidence compared to NAs monotherapy (1.2% vs. 4.9%, p<0.001), with a hazard ratio of 3.03 (95% CI: 1.82–5.06) after PSM. The protective effect was most pronounced in cirrhotic patients (absolute risk reduction 8.8%, NNT = 11). A novel nomogram incorporating treatment modality, AFP, cirrhosis, age, and other variables demonstrated excellent predictive accuracy (5-year AUC: 0.888 in derivation, 0.956 in validation cohorts), outperforming existing HCC prediction models. Conclusions: IFN-based therapy significantly reduces HCC risk in low-HBsAg CHB patients, particularly those with cirrhosis. We developed and validated a dynamic prediction model that may facilitate personalized surveillance and treatment decisions in functionally cured patients.
SN - 1664-3224
ER -