Work

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

Year: 2026

Type: article

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.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1955742