Ultra-high sensitivity HBsAg assay can diagnose HBV reactivation following rituximab-based therapy in patients with lymphoma
Ultra-high sensitivity HBsAg assay can diagnose HBV reactivation following rituximab-based therapy in patients with lymphoma
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DOI：
10.1016/j.jhep.2020.03.009
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发表时间：
2020-08-01
影响因子：
25.7
通讯作者：
Mizokami, Masashi
中科院分区：
文献类型：
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作者：
Kusumoto, Shigeru;Tanaka, Yasuhito;Mizokami, Masashi
背景与目的：在接受抗cd20抗体治疗淋巴瘤的患者中，HBV再激活是一种风险。本事后分析的目的是评估超高灵敏度HBsAg检测在指导淋巴瘤和解决HBV感染患者预防性抗病毒治疗中的有效性，使用来自HBV DNA监测研究的前瞻性存储样本。方法：252例患者中22例确认HBV再激活（定义为HBV DNA水平>= 11 IU/ml）。在基线、确认HBV再激活和HBV再激活后进行常规HBsAg检测（ARCHITECT，临界值：0.05 IU/ml）和采用半自动免疫复合物转移化学发光酶技术（ICT-CLEIA，临界值：0.0005 IU/ml）的超高灵敏度HBsAg检测。结果：4例患者采用ICT-CLEIA检测基线HBsAg；在所有这些实验中，具有高复制能力的前突变体都被重新激活。在基线时检测到HBV DNA低于定量水平的6例患者中，5例显示HBV再激活，其中3例有前期突变。ARCHITECT和ICT-CLEIA HBsAg检测在HBV再激活时或HBV再激活后的下一个采样的灵敏度分别为18.2%（4 / 22）和77.3%（17 / 22）。在ICT-CLEIA检测不到的5例患者中，2例患者HBV再激活自发消退。所有6例preore突变（包括preS缺失）再激活的患者都可以在HBV再激活的早期阶段通过ICT-CLEIA HBsAg检测进行诊断。多因素分析显示，抗乙肝病毒滴度低于10 mIU/ml、检测到HBV DNA但低于定量水平、基线时ICT-CLEIA检测到HBsAg是HBV再激活的独立危险因素(校正危险比分别为15.4、31.2和8.7
Background & Aims: HBV reactivation is a risk in patients receiving anti-CD20 antibodies for the treatment of lymphoma. The purpose of this post hoc analysis was to evaluate the efficacy of an ultra-high sensitivity HBsAg assay to guide preemptive antiviral treatment in patients with lymphoma and resolved HBV infections using prospectively stored samples from an HBV DNA monitoring study.Methods: HBV reactivation (defined as HBV DNA levels of >= 11 IU/ml) was confirmed in 22 of 252 patients. A conventional HBsAg assay (ARCHITECT, cut-off value: 0.05 IU/ml) and an ultra-high sensitivity HBsAg assay employing a semi-automated immune complex transfer chemiluminescence enzyme technique (ICT-CLEIA, cut-off value: 0.0005 IU/ml) were performed at baseline, at confirmed HBV reactivation and monitored after HBV reactivation.Results: Baseline HBsAg was detected using ICT-CLEIA in 4 patients; in all of whom precore mutants with high replication capacity were reactivated. Of the 6 patients with HBV DNA detected below the level of quantification at baseline, 5 showed HBV reactivation and 3 of the 5 had precore mutations. Sensitivity for detection by ARCHITECT and ICT-CLEIA HBsAg assays at HBV reactivation or the next sampling after HBV reactivation was 18.2% (4 of 22) and 77.3% (17 of 22), respectively. Of the 5 patients undetectable by ICT-CLEIA, HBV reactivation resolved spontaneously in 2 patients. All 6 patients reactivated with precore mutations including preS deletion could be diagnosed by ICT-CLEIA HBsAg assay at an early stage of HBV reactivation. Multivariate analysis showed that an anti-HBs titer of less than 10 mIU/ml, HBV DNA detected but below the level of quantification, and HBsAg detected by ICT-CLEIA at baseline were independent risk factors for HBV reactivation (adjusted hazard ratios, 15.4, 31.2 and 8.7, respectively; p