Internal Medicine Service, Guadalajara University Hospital, University of Alcalá, Guadalajara 19002, Spain.
Department of Biology of Systems, University of Alcalá, Alcalá de Henares (Madrid) 28805, Spain.
World J Gastroenterol. 2018 May 7;24(17):1825-1838. doi: 10.3748/wjg.v24.i17.1825.
Chronic hepatitis B (CHB) remains a challenging global health problem, with nearly one million related deaths per year. Nucleos(t)ide analogue (NA) treatment suppresses viral replication but does not provide complete cure of the hepatitis B virus (HBV) infection. The accepted endpoint for therapy is the loss of hepatitis B surface antigen (HBsAg), but this is hardly ever achieved. Therefore, indefinite treatment is usually required. Many different studies have evaluated NA therapy discontinuation after several years of NA treatment and before HBsAg loss. The results have indicated that the majority of patients can remain off therapy, with some even reaching HBsAg seroconversion. Fortunately, this strategy has proved to be safe, but it is essential to consider the risk of liver damage and other comorbidities and to ensure a close follow-up of the candidates before considering this strategy. Unanswered questions remain, namely in which patients could this strategy be effective and what is the optimal time point at which to perform it. To solve this enigma, we should keep in mind that the outcome will ultimately depend on the equilibrium between HBV and the host's immune system. Viral parameters that have been described as good predictors of response in HBeAg(+) cases, have proven useless in HBeAg(-) ones. Since antiviral immunity plays an essential role in the control of HBV infection, we sought to review and explain potential immunological biomarkers to predict safe NA discontinuation in both groups.
慢性乙型肝炎（CHB）仍然是一个具有挑战性的全球健康问题，每年因此相关死亡人数接近 100 万。核苷（酸）类似物（NA）治疗可抑制病毒复制，但不能完全治愈乙型肝炎病毒（HBV）感染。治疗的公认终点是乙型肝炎表面抗原（HBsAg）的丢失，但这几乎从未实现过。因此，通常需要进行无限期治疗。许多不同的研究已经评估了在 HBsAg 丢失之前进行数年 NA 治疗后的 NA 治疗停药。结果表明，大多数患者可以停止治疗，有些患者甚至可以达到 HBsAg 血清转换。幸运的是，这种策略已被证明是安全的，但在考虑这种策略之前，必须考虑到肝损伤和其他合并症的风险，并确保对候选者进行密切随访。仍然存在一些未解决的问题，即哪些患者可以从该策略中受益，以及进行该策略的最佳时间点是什么。为了解决这个谜团，我们应该记住，最终的结果将取决于 HBV 与宿主免疫系统之间的平衡。在 HBeAg（+）病例中被描述为良好反应预测因子的病毒参数，在 HBeAg（-）病例中已证明无用。由于抗病毒免疫在控制 HBV 感染中起着至关重要的作用，我们试图回顾和解释潜在的免疫标志物，以预测两组患者中安全的 NA 停药。
