治疗结束时“双阴性”HBV水平降低了复发风险

StephenW

‘Double negative’ HBV levels at end of treatment mark lower relapse risk

Fan R, et al. Clin Gastroenterol Hepatol. 2019;doi:10.1016/j.cgh.2019.07.046.
July 29, 2019

Patients who demonstrated negative results from tests for both hepatitis B DNA and RNA at the cessation of nucleos(t)ide treatment were less likely to experience clinical or virological relapse years later compared with those with only one negative test result.

In the study published in Clinical Gastroenterology and Liver Disease, researchers explained that although patients positive for HBV e-antigen patients may discontinue NA if they achieve therapeutic endpoints, the risk of off-treatment relapse remains still high. “Double negative” tests results may therefore provide a potent biomarker to guide treatment discontinuation.


Rong Fan, MD, from the Southern Medical University in China, and colleagues enrolled 130 patients in an evaluation cohort who had ceased treatment for chronic HBV.

After 4 years, patients who had HBV DNA results of “target not detected” at end of treatment had lower incidence of clinical relapse compared with those with either HBV DNA less than 20 IU/mL (20% vs. 39.8%; P = .036) or more than 20 IU/mL (40%; P = .036). Similarly, those with negative HBV RNA results had a lower risk for clinical relapse (15.3% vs. 37%; P = 0.029).

However, patients with both negative DNA and RNA status at end of treatment had the lowest risk for clinical relapse compared with those with either positive HBV DNA or RNA (8% vs. 31.4%; P = .018) with a predictive value of 92%.

Multivariate analysis revealed that HBV DNA and RNA levels at end of treatment were the strongest independent predictors of clinical relapse (HR = 4.54; 95% CI, 1.08-19) and virologic relapse (HR = 11.1; 95% CI, 2.69-45.8).

Additionally, in a validation cohort comprising 40 patients with HBeAg-positive infection, the researchers found that those with double negative status had numerically lower clinical relapse rates than those who were positive for either HBV DNA or RNA (15.4% vs. 33.3%).

“Based on these findings, we propose that the overall HBV nucleic acid level ... could be used as a reliable biomarker for guiding NA discontinuation decisions,” Fan and colleagues wrote. “Meanwhile, there is a need to develop a new kit that can directly detect overall HBV nucleic acid levels for better, simpler monitoring of treatment response and guidance for withdrawal.” – by Talitha Bennett

Disclosure: The study was funded by National Science and Technology Major Project, the National Natural Science Foundation of China, the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program and Novartis. Fan reports no relevant financial disclosures. Please see the full study for all other authors’ relevant financial disclosures.

StephenW

治疗结束时“双阴性”HBV水平降低了复发风险

Fan R，et al。 Clin Gastroenterol Hepatol。 2019; DOI：10.1016 / j.cgh.2019.07.046。
2019年7月29日

在核苷（t）治疗停止时对乙型肝炎DNA和RNA检测结果呈阴性的患者与仅有一个阴性检测结果的患者相比，在几年后出现临床或病毒学复发的可能性较小。

在临床胃肠病学和肝病发表的研究中，研究人员解释说，虽然HBV e抗原患者阳性的患者如果达到治疗终点可能会中断NA，但治疗后复发的风险仍然很高。 “双阴性”测试结果可能因此提供有效的生物标志物来指导治疗中止。


来自中国南方医科大学的荣范医师和同事在一个已经停止慢性HBV治疗的评估队列中招募了130名患者。

4年后，治疗结束时“未检测到目标”HBV DNA结果的患者临床复发率低于HBV DNA低于20 IU / mL的患者（20％vs。39.8％; P =。 036）或大于20 IU / mL（40％; P = .036）。类似地，HBV RNA阴性的患者临床复发风险较低（15.3％对37％; P = 0.029）。

然而，与HBV DNA或RNA阳性的患者相比，治疗结束时DNA和RNA状态均为负的患者临床复发风险最低（8％vs。31.4％; P = .018），预测值为92 ％。

多变量分析显示，治疗结束时HBV DNA和RNA水平是临床复发的最强独立预测因子（HR = 4.54; 95％CI，1.08-19）和病毒学复发（HR = 11.1; 95％CI，2.69-45.8） 。

此外，在验证队列中包括40名HBeAg阳性感染患者，研究人员发现那些双重阴性患者的临床复发率在数值上低于HBV DNA或RNA阳性的患者（15.4％对33.3％）。

“基于这些发现，我们建议整体HBV核酸水平......可以作为指导NA中止决定的可靠生物标志物，”Fan及其同事写道。 “同时，需要开发一种新的试剂盒，可以直接检测HBV的总体核酸水平，以便更好，更简单地监测治疗反应和退出指导。” - 作者：Talitha Bennett

披露：该研究由国家科技重大项目，国家自然科学基金，广东珠江人才项目和诺华地方创新研究团队项目资助。 Fan报告没有相关的财务披露。请参阅完整的研究报告所有其他作者的相关财务披露。