A Systematic Review and Model-Based Meta-Analysis of Pegylated-Interferon-α-Induced HBsAg Loss in Chronic Hepatitis B Virus Infection

This study synthesizes data from a large body of clinical trials to evaluate rates of hepatitis B surface antigen (HBsAg) loss following pegylated interferon-alpha (Peg-IFNα) treatment in chronic hepatitis B (CHB), using a model-based meta-analysis (MBMA) at end of treatment and 24 weeks post-treatment. The analysis identifies longer treatment duration, lower baseline hepatitis B surface antigen levels, and hepatitis B e-antigen (HBeAg) status as key drivers of response variability across studies, substantially reducing unexplained heterogeneity. Importantly, the work translates these insights into practical value by providing a quantitative framework to predict expected response rates, inform patient selection, optimize clinical trial design, and support simulation and in silico trial approaches. By turning heterogeneous clinical evidence into actionable, predictive guidance, the study establishes a robust benchmark for evaluating existing and emerging hepatitis B virus therapies and advances more efficient, model-informed development strategies aimed at achieving functional cure.