Off-treatment virologic relapse and outcomes of re-treatment in chronic hepatitis B patients who achieved complete viral suppression with oral nucleos(t)ide analogs.
Off-treatment virologic relapse and outcomes of re-treatment in chronic hepatitis B patients who achieved complete viral suppression with oral nucleos(t)ide analogs.
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DOI：
10.1186/1471-2334-14-439
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发表时间：
2014-08-13
影响因子：
3.7
通讯作者：
Kim JW
中科院分区：
文献类型：
--
作者：
Sohn HR;Min BY;Song JC;Seong MH;Lee SS;Jang ES;Shin CM;Park YS;Hwang JH;Jeong SH;Kim N;Lee DH;Kim JW
在既往使用核苷类似物（NA）治疗达到完全病毒学抑制的慢性B型肝炎（CH B）患者中，停药后病毒学应答的持久性尚未完全阐明。本研究旨在评估停止治疗后病毒学复发率，并描述在完全病毒学抑制后停止口服NA的CHB患者随后再治疗的结局。95例显示病毒学完全抑制的CHB患者停用NAs：恩替卡韦、拉米夫定和克来夫定分别为67例、15例和13例。HBeAg阳性和阴性CHB患者在停药前分别接受6个月和12个月的巩固治疗。病毒学复发采用与停药前诱导完全病毒学应答相同的NA进行管理。12个月和24个月的累积病毒学复发率分别为73.8%和87.1%。复发率与HBeAg阳性、HBeAg血清转换和口服NA类型无关。在多变量分析中，口服NA治疗的持续时间是与停药后病毒学复发相关的唯一显著预测因素。虽然大多数患者恢复了完全的病毒学抑制，但一些患者对初始NA的再治疗没有反应，并出现了基因型耐药。NA巩固治疗6个月和12个月分别与HBeAg阳性和阴性CHB患者的高停药病毒学复发相关。具有高耐药遗传屏障的药物应被视为CHB停药后复发的挽救治疗。本文的在线版本（doi：10.1186/1471-2334-14-439）包含补充材料，可供授权用户使用。
The durability of off-treatment virologic responses has not been fully elucidated in chronic hepatitis B (CHB) patients who have previously achieved complete virologic suppression with nucleos(t)ide analog (NA) therapy. This study aimed to assess off-treatment virologic relapse rates and to characterize the outcomes of subsequent re-treatment in CHB patients who have discontinued oral NA following complete virologic suppression. Ninety-five CHB patients who showed complete virologic suppression were withdrawn from NAs: entecavir, lamivudine, and clevudine in 67, 15, and 13 patients, respectively. Consolidation therapy was given for 6 and 12 months for HBeAg-positive and -negative CHB, respectively, before cessation. Virologic relapse was managed with the same NA that had induced complete virologic response before discontinuation. The cumulative rates of virologic relapse at 12 and 24 months were 73.8% and 87.1%, respectively. The relapse rates were independent of HBeAg positivity, HBeAg seroconversion, and type of oral NA. In a multivariate analysis, duration of oral NA therapy was the only significant predicting factor associated with off-treatment virologic relapse. Although the majority of patients regained complete virologic suppression, some patients did not respond to re-treatment with the initial NA and developed genotypic resistance. NA consolidation therapy for 6 and 12 months is associated with high off-treatment virologic relapse in HBeAg-positive and -negative CHB patients, respectively. Drugs with high genetic barriers to resistance should be considered as a rescue therapy for off-treatment relapse in CHB. The online version of this article (doi:10.1186/1471-2334-14-439) contains supplementary material, which is available to authorized users.