Predictive value of hepatic, hematological, and immunological markers and their temporal dynamics in chronic...

Hepatitis B virus (HBV) infection remains a major global health burden. While interferon-alpha (IFNα) therapy demonstrates antiviral and immunomodulatory effects, reliable prognostic markers for sustained response are needed. Transaminases, hematological parameters, and cytokines may serve as potential predictors, but their dynamic changes during IFNα therapy remain poorly characterized. In this prospective real-world study, 181 chronic HBV (CHB) patients received weekly PEG-IFNα-2b for 48 weeks, with serial assessments of virological (HBV DNA, hepatitis B surface antigen [HBsAg]), biochemical (alanine aminotransferase [ALT], aspartate aminotransferase [AST]), hematological (white blood cell [WBC], platelets), and cytokine (interleukin [IL]-4/6, tumor necrosis factor-alpha [TNF-α], IFN-γ) profiles every 4 weeks. The primary outcome was functional cure of CHB. Statistical analyses included (i) generalized linear models (GLMs) evaluating associations between cure status and predictor trends; (ii) Cox regression identifying prognostic factors; (iii) trajectory clustering of biomarker dynamics. Results indicated that sustained declines in ALT (β = -0.025, P = 0.029) and AST (β = -0.033, P = 0.039) were predictive of functional cure, as confirmed by Cox models (ALT HR = 1.003, P = 0.002; AST HR = 1.004, P = 0.013). Additionally, the maximum monthly increase in WBC was independently associated with functional cure (β = 0.380, P = 0.009). Elevated baseline IL-4 (HR = 1.144, P < 0.001) and longitudinal changes in IL-4/IFN-γ also predicted functional cure (P < 0.05), although the inclusion of cytokines did not enhance model performance. Trajectory analysis further identified distinct patterns of ALT, AST, and hematological parameter changes linked to functional cure. In conclusion, ALT and AST remain robust predictors of the functional cure of CHB following IFNα therapy, while dynamic WBC and cytokine profiles provide supplementary prognostic value.IMPORTANCEInterferon-alpha (IFNα) therapy, known for its antiviral and immunomodulatory effects, lacks reliable predictors of functional treatment response. This study addresses this gap by systematically analyzing dynamic changes in biochemical, hematological, and immunological markers during IFNα therapy. The findings validate alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as robust predictors for functional cure of chronic Hepatitis B virus (CHB), while highlighting the complementary prognostic value of within-visit fluctuations in white blood cell (WBC) counts and cytokine profiles, particularly IL-4 and IFN-γ. Furthermore, the study identifies longitudinal stability in ALT and AST levels, along with specific hematological patterns characterized by initial decline followed by gradual recovery, as predictors of functional cure. By employing generalized linear models, Cox regression, and trajectory clustering, this research provides a comprehensive framework for understanding functional treatment response dynamics of CHB. These findings are significant for clinicians and researchers aiming to refine therapeutic strategies and achieve better patient outcomes in CHB.