[A possible mechanism for low-level viremia occurrence in nucleos(t)ide analog-treated chronic hepatitis B patients].

The first-line nucleos(t)ide analogs (NAs) based antiviral drugs can effectively inhibit HBV replication and slow down the progression of chronic hepatitis B. However, about 20% of patients receiving standard NAs antiviral therapy will still develop low-level viremia (LLV). Therefore, understanding the occurrence mechanism of LLV will help to optimize antiviral treatment regimens and improve the prognosis of patients with chronic hepatitis B. This article systematically summarizes the possible mechanisms of LLV occurrence, and the important factor of NAs failure. Taking into account the unique limitations of NAs competitive inhibition of virus replication, weakening host's immune response is not enough to directly eliminate infected hepatocytes. This makes it difficult to achieve a complete virological response in some patients with the active compensatory proliferation of residual infected hepatocytes and the accompanying effective removal or dilution of covalent, closed, circular DNA (cccDNA) pools. Therefore, it is speculated that activating host immunity can eliminate infected liver cells and may be more conducive to address LLV.一线抗病毒药物核苷（酸）类似物（NAs）能够有效抑制HBV复制，减缓慢性乙型肝炎进程，但仍约有20%的接受规范NAs抗病毒治疗的患者会发生低病毒血症（LLV）。厘清LLV发生的机制将有助于优化慢性乙型肝炎患者抗病毒治疗方案，改善患者的预后。系统总结LLV发生的可能机制，认为除了NAs竞争性抑制病毒复制所特有的局限性外，宿主较弱的免疫应答使其直接清除感染肝细胞的能力不足，难以诱发残余感染肝细胞的活跃代偿性增殖及伴随的共价闭合环状DNA池被有效清除或稀释，可能也是NAs在部分患者中无法实现完全病毒学应答的重要因素。据此推测，通过激活宿主免疫以清除感染肝细胞，在解决LLV上可能更有优势。.