Zheng Jiarui, Wang Zilong, Huang Linxiang, Qiu Zixuan, Xie Yandi, Jiang Suzhen, Feng Bo
Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.
Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.
Virus Res. 2025 Jan;351:199507. doi: 10.1016/j.virusres.2024.199507. Epub 2024 Dec 13.
Chronic hepatitis B (CHB) is a significant global health issue affecting approximately 254 million individuals worldwide. Achieving the loss of hepatitis B surface antigen (HBsAg), either with or without seroconversion to hepatitis B surface antibody (HBsAb), is regarded as a functional cure and the optimal goal for addressing CHB, and can be achieved through various approaches, including induction with nucleos(t)ide analogues (NAs), induction with pegylated interferon alpha (PegIFNα), and spontaneous clearance of HBsAg. Spontaneous clearance of HBsAg is rare, while NAs can directly inhibit HBV DNA, they are unable to act on covalently closed circular DNA (cccDNA), hence inhibiting HBsAg production or clearing HBsAg is extremely challenging. On the other hand, functional cure based on PegIFNα shows good long-term durability, but over 10 % of patients still experience relapse, mostly within 48 weeks after functional cure. Factors related to CHB functional cure with antiviral therapy are complex, including host factors, viral factors, environmental factors, etc. The integration of HBV DNA into liver cells, persistence of HBV cccDNA, insufficient B cell responses and compromised T cell function pose significant barriers to HBV clearance. Therefore, this study systematically reviewed the relevant factors and potential mechanisms influencing functional cure CHB, which can provide a basis for personalized treatment, help predict treatment outcomes and assess prognosis, and provide theoretical support for the advancement of novel treatment strategies and medications.
慢性乙型肝炎（CHB）是一个重大的全球健康问题，全球约有2.54亿人受其影响。实现乙肝表面抗原（HBsAg）消失，无论有无血清学转换为乙肝表面抗体（HBsAb），都被视为功能性治愈，是解决CHB的最佳目标，可通过多种方法实现，包括核苷（酸）类似物（NAs）诱导、聚乙二醇化干扰素α（PegIFNα）诱导以及HBsAg的自发清除。HBsAg的自发清除很少见，虽然NAs可直接抑制HBV DNA，但它们无法作用于共价闭合环状DNA（cccDNA），因此抑制HBsAg产生或清除HBsAg极具挑战性。另一方面，基于PegIFNα的功能性治愈显示出良好的长期持久性，但超过10% 的患者仍会复发，大多在功能性治愈后的48周内。抗病毒治疗实现CHB功能性治愈的相关因素复杂，包括宿主因素、病毒因素、环境因素等。HBV DNA整合入肝细胞、HBV cccDNA的持续存在、B细胞反应不足和T细胞功能受损对HBV清除构成重大障碍。因此，本研究系统综述了影响CHB功能性治愈的相关因素和潜在机制，可为个性化治疗提供依据，有助于预测治疗结果和评估预后，并为新治疗策略和药物的推进提供理论支持。
