Abstract: Chronic hepatitis B (CHB) remains a major global public health issue, and achieving clinical cure, defined as clearance of hepatitis B surface antigen (HBsAg), is a primary goal of current antiviral therapy. Pegylated interferon alpha (PEG-IFNα) possesses both immunomodulatory and direct antiviral effects, making it a key therapeutic agent for promoting clinical cure in CHB. However, its efficacy varies considerably among individuals, and the clinical cure rate is influenced by multiple interacting factors, including virological, host-related, and treatment-related variables. This review focuses on the factors influencing the achievement of clinical cure with PEG-IFNα therapy in CHB. Current evidence indicates that virological markers are helpful in identifying favorable populations, host immune response characteristics are closely associated with treatment response, genetic polymorphisms may affect individual efficacy by modulating interferon signaling pathways, and appropriate selection of treatment strategies also significantly impacts the clinical cure rate. This review also critically evaluates current research bottlenecks, such as the limited predictive efficacy of single markers and insufficient prospective validation, and proposes that future efforts should integrate multidimensional dynamic indicators to construct personalized predictive models, thereby enabling precise screening of favorable populations and optimization of treatment decisions, ultimately further improving the clinical cure rate of CHB.

Key words: Pegylated interferon alpha, Chronic hepatitis B, Clinical cure, Influencing factors, Virology, Immunology