Steatosis and Interferon Associated with HBsAg Immune Control in Chronic Hepatitis B: A Real-World Propensity Score-Matched Study

<b>Background/Objectives:</b> The baseline determinants of functional cure in chronic hepatitis B (CHB) are largely unknown. By applying propensity score matching (PSM) to real-world data, we aimed to identify traits associated with functional cure. <b>Methods:</b> We included CHB cases which achieved a functional cure and randomly selected non-achievers from patients followed from 2000 to 2020. Initial screening of baseline candidate traits was conducted using PSM-balanced cases and controls. Subsequently, through multiple rounds of leave-one-covariate-out on the balanced cohorts, we validated the impact of these traits using survival analysis. <b>Results:</b> In total, 85 cases (mean age: 35.78; female/male: 23/62) were compared with 247 controls (mean age: 37.08; female/male: 80/167, out of 3666), with a median follow-up of 69.56 months. Steatosis and interferon (IFN) treatment were significantly more frequent in the cases, as confirmed by forest plots showing significant hazard ratios. During validation, whether through balancing all covariates or leave-one-covariate-out matching, both steatosis and exposure to IFN resulted in a higher number of functional cures and HBsAg seroconversions. Further comparisons revealed that add-on or monotherapy outperformed switching (from IFN to NUC), while the de novo (IFN + NUC, followed by NUC) approach was not observed. <b>Conclusions:</b> We confirmed that individuals with steatosis at baseline or those who received IFN were more likely to achieve HBsAg immune control, with monotherapy/add-on therapy being emphasized.