Abstract: Objective To summarize the research progress in the clinical safety of antiviral drugs used for chronic hepatitis B and to provide references to related clinical applications and drug development. Methods Based on literature available in PubMed, the China National Knowledge Infrastructure (CNKI), and Wanfang Data over the past five years (between January 2020 and June 2025), this study traced the research progress in marketed drugs as well as agents under clinical development. The safety profiles of both monotherapies and combination therapies were assessed. Results Marketed nucleoside analogues proved to be relatively safe, but long-term use called for vigilance on potential nephrotoxicity, disturbances in bone metabolism, adverse pregnancy outcomes, and dyslipidemia. During interferon therapy, special attention needed to be paid to its potential impacts on the hematopoietic system, neuropsychiatric function, and autoimmune disorders. For investigational drugs under clinical development, hepatic dysfunction, immune-related adverse events, and injection-site reactions were worthy of attention. Conclusion Nucleoside analogues can play a pivotal role in suppressing viral replication, improving liver histology, and reducing the incidence of hepatocellular carcinoma. Despite the multiple systems in adverse events, the overall incidence is low and symptoms are mild. For long-term users, safety is a big concern. Interferon treatment should proceed under the supervision of qualified physicians, with constant monitoring of adverse reactions. Future development of novel pharmaceuticals is to revolve around key stages in the viral life cycle or modulation of host immunity in order to offer safer and more effective options for a complete cure.

Key words: Chronic Hepatitis B, Antiviral Drugs, Nucleoside Analogues, Interferon, Adverse Drug Reactions