Insulin Resistance as a Dynamic Correlate of Fibrosis Status in Chronic Hepatitis B: A Visit-Level Longitudinal Risk Stratification Framework

Background: Viral replication is a major factor in chronic hepatitis B (CHB). Still, the extent to which host metabolic dysfunction contributes to fibrosis risk remains unclear, particularly in studies that follow patients over time. Because most research relies solely on baseline assessments, it may overlook how metabolic changes and fibrosis interact as the disease progresses. Methods: We conducted a retrospective longitudinal cohort study of 304 adults with CHB using electronic medical records collected across 4 visits over 18 months. Repeated metabolic parameters and non-invasive fibrosis indices were examined using population-averaged and mixed-effects models. The associations we observed represent time-specific co-variation between exposures and outcomes measured at the same time point, rather than earlier predictors of later outcomes. Results: Across 1216 person-visits, 421 visit-level fibrosis risk events were recorded (34.6%). Incident clustered metabolic abnormalities occurred at a rate of 21.43 per 100 person-years. Among the metabolic syndrome components, insulin resistance showed the most consistent independent association with visit-level fibrosis risk status. In contrast, after adjustment, longitudinal trends in BMI, lipid measures, and transaminases did not independently distinguish patients with fibrotic progression. A practical clinical model based on age, AST, platelet count, and fasting glucose demonstrated moderate discrimination across risk strata (AUC = 0.772). Conclusions: In CHB, insulin resistance is consistently linked to visit-level fibrosis risk status. Longitudinal metabolic monitoring using routine clinical data provides a practical, scalable way to assess fibrosis risk, especially in resource-limited settings. These findings support incorporating time-based metabolic assessment into CHB care pathways alongside virological factors.