Relapses are observed in most hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B patients who discontinue treatment with nucleos(t)ide analogues (NAs); however, the rates of relapse vary widely among studies, and whether all patients with relapse need retreatment is unclear. The aim of this study was to assess the impact of different definitions on the rates of posttreatment relapse and therefore on the probability of retreatment in patients who have discontinued effective long‐term NA therapy. In total, 130 HBeAg‐negative chronic hepatitis B patients without cirrhosis and before NA treatment were included. All had on‐therapy virological remission for ≥24 months and close follow‐up for ≥12 months after stopping NA treatment or until retreatment, which started on stringent predefined criteria. Relapses rates based on several predetermined definitions of virological and perhaps biochemical criteria were assessed. The median duration of therapy was 60 months and the median duration of on‐therapy virological remission was 43 months. During a median off‐NAs follow‐up of 15 months, no patient experienced liver decompensation or died. Cumulative relapse rates were 2%‐49%, 4%‐73%, 11%‐82%, and 16%‐90% at 3, 6, 12, and 24 months, respectively, whereas cumulative retreatment rates were 15%, 22%, and 40% at 6, 12, and 24 months, respectively, after discontinuation of NA therapy. No patient characteristic was independently associated with the probability of relapse based on at least two definitions or of retreatment. Conclusion: In HBeAg‐negative chronic hepatitis B patients who discontinue NA therapy, the definition of relapse has a great impact on off‐NAs relapse rates and potentially on the probability of retreatment. Regardless of definition, off‐NAs relapses cannot be easily predicted by patient characteristics. A substantial proportion of such patients may not require retreatment if stringent criteria are adopted. (Hepatology 2017).

中文翻译：

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HBeAg 阴性慢性乙型肝炎停用口服抗病毒药物后复发定义的意义

大多数乙型肝炎e抗原（HBeAg）阴性慢性乙型肝炎患者停止使用核苷（酸）类似物（NAs）治疗后会出现复发；然而，研究之间的复发率差异很大，是否所有复发患者都需要再次治疗尚不清楚。本研究的目的是评估不同定义对治疗后复发率的影响，从而对已停止有效长期 NA 治疗的患者再次治疗的可能性进行评估。共纳入 130 名 HBeAg 阴性慢性乙型肝炎患者，无肝硬化且未接受 NA 治疗。所有患者的治疗中病毒学缓解≥24 个月，并在停止 NA 治疗后或直至再治疗后密切随访≥12 个月，这开始于严格的预定义标准。评估了基于病毒学和生化标准的几个预定定义的复发率。治疗的中位持续时间为 60 个月，治疗中病毒学缓解的中位持续时间为 43 个月。在 15 个月的中位非 NAs 随访期间，没有患者出现肝功能失代偿或死亡。3、6、12 和 24 个月的累积复发率分别为 2%-49%、4%-73%、11%-82% 和 16%-90%，而累积再治疗率为 15%、22分别在停止 NA 治疗后 6、12 和 24 个月时的 % 和 40%。根据至少两种定义或再治疗，没有患者特征与复发概率独立相关。结论：在停止 NA 治疗的 HBeAg 阴性慢性乙型肝炎患者中，复发的定义对非 NAs 的复发率和再治疗的可能性有很大影响。无论定义如何，患者特征都不能轻易预测非 NAs 的复发。如果采用严格的标准，很大一部分此类患者可能不需要再治疗。（肝病学 2017）。