Serum Level of Antibodies Against Hepatitis B Core Protein Is Associated With Clinical Relapse After Discontinuation of Nucleos(t)ide Analogue Therapy
Serum Level of Antibodies Against Hepatitis B Core Protein Is Associated With Clinical Relapse After Discontinuation of Nucleos(t)ide Analogue Therapy
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乙型肝炎核心蛋白抗体的血清水平与核苷（酸）类似物治疗停止后的临床复发相关
DOI：
10.1016/j.cgh.2018.05.047
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发表时间：
2019-01-01
影响因子：
12.6
通讯作者：
Peng, Jie
中科院分区：
文献类型：
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作者：
Chi, Heng;Li, Zhandong;Peng, Jie
背景与目的：抗乙肝病毒核心蛋白(抗-HBc)抗体水平与慢性乙肝患者对核糖核酸(T)类似物和干扰素(Peg)治疗的反应有关。我们进行了一项前瞻性研究，以确定血清总抗HBc水平(免疫球蛋白M和G)水平是否与停用类似物治疗后的临床复发有关。方法：收集2012年11月至2016年7月在广州一家学术医院招募的慢性乙肝患者按预先指定的停用标准停用类似物治疗的数据。对患者进行了跟踪调查，直至2017年2月。我们在每次就诊时进行全面的生化和病毒学测试，并在治疗停止后的两年内(在基线和第4、8、12、24、48和96周)定量检测抗-HBc。主要终点是临床复发，定义为HBVDNA和GT；2000IU/mL水平和丙氨酸氨基转移酶水平是正常上限的两倍以上-这些也是停药的标准。结果：我们跟踪观察了100名患者(核素(T)类似物治疗开始时HBe抗原阳性的71%，恩替卡韦或替诺福韦治疗的43%)，中位时间为2.5年。39名患者出现临床复发(46%的患者在停药后第4年)。治疗结束时抗-HBc水平高(危险比[HR]，0.31/logIU/ml；P=0.002)和治疗结束时低水平的Hb表面抗原(HbsAg)(HR，1.71/logIU/mL；P=.032)与在调整年龄、开始核素(T)类似物治疗、HBeAg状态和巩固治疗时间后临床复发的风险降低有关。在第4年，在治疗结束时抗-HBc水平为1000IU/ml的患者中，21%的患者出现了临床复发，而在治疗结束时抗-HBc水平为85%的患者中，这一比例为85%
BACKGROUND & AIMS: Levels of antibodies against the hepatitis B virus (HBV) core protein (anti-HBc) have been associated with response to nucleos(t)ide analogue and (peg) interferon therapy in patients with chronic HBV infection. We performed a prospective study to determine whether the total serum level of anti-HBc level (immunoglobulins M and G) is associated with clinical relapse after discontinuation of nucleos(t)ide analogue-based therapy.METHODS: We collected data from patients with chronic HBV infection who discontinued nucleos(t)ide analogue therapy according to pre-specified stopping criteria, recruited from November 2012 through July 2016 at an academic hospital in Guangzhou, China. Patients were followed through February 2017. We performed comprehensive biochemical and virologic tests at every visit, and anti-HBc was quantified for 2 years after treatment cessation (at baseline and weeks 4, 8, 12, 24, 48, and 96). The primary endpoint was clinical relapse, defined as level of HBV DNA >2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal-these were also the criteria for retreatment.RESULTS: We followed 100 patients (71% positive for HB e antigen [HBeAg] at the start of nucleos(t)ide analogue therapy, 43% treated with entecavir or tenofovir) for a median of 2.5 years after stopping therapy. Clinical relapse occurred in 39 patients (in 46% of patients at year 4 after discontinuation). High level of anti-HBc at the end of treatment (hazard ratio [HR], 0.31 per log IU/mL; P = .002) and low level of HB surface antigen (HBsAg) at the end of treatment (HR, 1.71 per log IU/mL; P = .032) were associated with a reduced risk of clinical relapse after adjusting for age, start of nucleos(t)ide analogue therapy, HBeAg-status, and consolidation therapy duration. At year 4, 21% of patients with anti-HBc levels at the end of treatment >= 1000 IU/mL developed a clinical relapse compared to 85% of patients with levels