Chronic hepatitis B virus (HBV) infection is the largest global cause of hepatocellular carcinoma (HCC). Current HBV treatment options include pegylated interferon-alpha and nucleos(t)ide analogues (NAs), which have been shown to be effective in reducing HBV DNA levels to become undetectable. However, the literature has shown that some patients have persistent risk of developing HCC. The mechanism in which this occurs has not been fully elucidated. However, it has been discovered that HBV’s covalently closed circular DNA (cccDNA) integrates into the critical HCC driver genes in hepatocytes upon initial infection; additionally, these are not targets of current NA therapies. Some studies suggest that HBV undergoes compartmentalization in peripheral blood mononuclear cells that serve as a sanctuary for replication during antiviral therapy. The aim of this review is to expand on how patients with HBV may develop HCC despite years of HBV viral suppression and carry worse prognosis than treatment-naive HBV patients who develop HCC. Furthermore, HCC recurrence after initial surgical or locoregional treatment in this setting may cause carcinogenic cells to behave more aggressively during treatment. Curative novel therapies which target the life cycle of HBV, modulate host immune response, and inhibit HBV RNA translation are being investigated.
慢性乙型肝炎病毒（HBV）感染是全球肝细胞癌（HCC）最主要的致病因素。目前针对HBV的治疗方案包括聚乙二醇化干扰素-α和核苷（酸）类似物（NAs），这些疗法已被证实能有效降低HBV DNA水平直至检测不到。然而，文献表明部分患者仍存在持续的HCC发生风险，其发生机制尚未完全阐明。研究发现，HBV在初始感染时其共价闭合环状DNA（cccDNA）会整合入肝细胞的关键HCC驱动基因中，而现有NAs疗法无法靶向该过程。另有研究提示，HBV在外周血单个核细胞中存在区室化分布现象，这可能在抗病毒治疗期间成为病毒复制的庇护所。本综述旨在深入探讨：为何HBV患者在经历多年病毒抑制后仍可能发展为HCC，且其预后较未接受治疗的HBV相关HCC患者更差；同时在此背景下，初始手术或局部治疗后出现的HCC复发，可能导致致癌细胞在治疗过程中表现出更强的侵袭性。目前针对HBV生命周期调控、宿主免疫应答调节及HBV RNA翻译抑制的新型根治性疗法正在研究中。
肿瘤(癌症)患者之家