AASLD2019[646]双重阴性HBV核酸（DNA- / RNA-） 预测核素（T）的非

StephenW

646
DOUBLE NEGATIVE HBV NUCLEIC ACID (DNA-/RNA-)
PREDICTS OFF-TREATMENT DURABILITY OF NUCLES(T)IDE
ANALOGUE IN A PROSPECTIVE COHORT
Rong Fan1, Bin Zhou1, Min Xu2, Deming Tan3, Junqi Niu4, Hao
Wang5, Hong Ren6, Xinyue Chen7, Maorong Wang8, Qin Ning9,
Guangfeng Shi10, Jifang Sheng11, Hong Tang12, Xuefan Bai13,
Shi Liu1, Fengmin Lu14, Jie Peng15, Jian Sun15, Qing Xie16, Jinlin
Hou15 and Chinese Chronic Hepatitis B Study Consortium, (1)
Nanfang Hospital, Southern Medical University, Guangzhou,
China, (2)8th People’s Hospital, Guangzhou, China, (3)
Xiangya Hospital, Central South University, Changsha, China,
(4)The First Hospital of Jilin University, (5)Peking University
People’s Hospital, Beijing, China, (6)Department of Infectious
Diseases, Institute for Viral Hepatitis, the Key Laboratory of
Molecular Biology for Infectious Diseases, Chinese Ministry
of Education, the Second Affiliated Hospital of Chongqing
Medical University, Chongqing, China, (7)Beijing Youan
Hospital, Capital Medical University, Beijing, China, (8)81st
PLA Hospital, Nanjing, China, (9)Tongji Hospital of Tongji
Medical College, Huazhong University of Science and
Technology, (10)Department of Infectious Diseases, Huashan
Hospital, Fudan University, Shanghai, China, (11)The First
Affiliated Hospital of Medical School of Zhejiang University,
Hangzhou, China, (12)West China Hospital, Chengdu,
China, (13)Tangdu Hospital, Xi’an, China, (14)School of
Basic Medical Sciences, Peking University Health Science
Center, Beijing, China, (15)Department of Infectious Diseases
, Nanfang Hospital, Southern Medical University, (16)
Department of Infectious Diseases, Ruijin Hospital, Shanghai
Jiaotong University School of Medicine
Background: The response durability after nuleos(t)ide
analogue (NAs) discontinuation in chronic hepatitis B (CHB)
was unsatisfactory The aim of this study was to determine
the performance of HBV DNA and HBV RNA as predictors
for durability Methods: The evaluation cohort included 130
HBeAg-positive patients (30 8 ± 6 9 years, 72 3% male)
from a multi-center prospective trial who stopped telbivudinebased
therapy after achieving HBeAg seroconversion and
HBV DNA <300 copies/mL for >48 weeks and were followed
up until clinical relapse occurred As validation, 40 patients
(36 5 ± 9 4 years, 72 5% male) treated with entecavir
or tenofovir before discontinuation were analyzed The
negative HBV DNA at end of treatment (EOT) was strictly
defined as “Target Not detected” by using COBAS Taqman
assay with LLOD of 20 IU/mL. The negative HBV RNA was
defined as both not targeted detection in RT-qPCR with two
different pairs of primers The primary off-treatment outcome
evaluated was clinical relapse, defined as HBV DNA >
2000 IU/mL plus ALT >2 × ULN. The secondary outcomes
included virologic relapse defined as HBV DNA >2000 IU/
mL and HBeAg reversion defined as the reappearance of
HBeAg at two consecutive protocol-defined visits.Results: In
the evaluation cohort, the 4-year cumulative rates of clinical
relapse, virologic relapse and HBeAg reversion were 30 8%,
54 7% and 16 8%, respectively The percentages of patients
with double negative HBV DNA and RNA (DNA-/RNA-),
mono negative HBV DNA (DNA-/RNA+), mono negative HBV
RNA (DNA+/RNA-), and double positive HBV DNA and RNA
(DNA+/RNA+) were 19 7% (25/127), 29 1% (37/127), 6 3%
(8/127) and 44 9% (57/127), respectively Patients with EOT
HBV DNA of “Target Not detected” had significantly lower
cumulative incidence of clinical relapse, than those with either
HBV DNA <20 or >20 IU/mL (20.0% vs. 39.8% vs. 40.0%,
P=0.036). Similarly, patients with negative EOT HBV RNA
level also had significantly lower risk of clinical relapse (15.3%
vs 37 0%, P =0 029) at off-treatment year 4 The multivariate
regression analysis showed that HBV DNA + RNA level at
EOT (either positive vs double negative) was the strongest
independent risk factor for clinical relapse (Hazard ratio [HR],
4.549; 95% confidence interval [CI], 1.089 - 19.002, P =0.038)
and virologic relapse (HR, 11 100; 95% CI, 2 690 - 45 809;
P =0 001), respectively At year 4, patients with EOT double
negative HBV DNA and RNA (DNA-/RNA-) had significantly
lower risk of clinical relapse than those with either positive
HBV DNA or RNA (8.0% [2/25] vs. 31.4% [32/102], P=0.018).
In the validation cohort, the patients with EOT HBV DNA-/
RNA- also had the lowest clinical relapse rate during up to
5.5-year follow-up (15.4% [2/13] vs. 33.3% [9/27], P=0.286).
Conclusion: Double negative HBV nucleic acid (DNA-/RNA-)
at EOT with more rigorous definition is a potent biomarker for
guiding NAs safety discontinuation in CHB HBeAg positive
patients.

StephenW

646
双重阴性HBV核酸（DNA- / RNA-）
预测核素（T）的非治疗耐久性
预期队列中的模拟
范凡1，周斌1，闵旭2，谭德明3，牛俊奇4，郝
王5，洪仁6，陈新月7，王茂荣8，秦宁9，
石广峰10，冀方盛11，洪堂12，白雪凡13，
石柳1，冯敏路14，介鹏15，孙健15，庆协16，金林
Hou15和中国慢性乙型肝炎研究联盟，（1）
南方医科大学南方医院，广州
中国（2）第八人民医院，中国广州（3）
中南大学湘雅医院，长沙，
（4）吉林大学第一医院，（5）北京大学
中国北京市人民医院，（6）传染科
疾病，病毒性肝炎研究所，重点实验室
中国卫生部传染病分子生物学
重庆市第二附属医院教育部
重庆医科大学，（7）北京佑安
首都医科大学附属医院，北京，（8）81
南京人民解放军医院，（9）同济同济医院
华中科技大学医学院
技术，（10）华山市传染病科
复旦大学附属医院，上海，（11）
浙江大学医学院附属医院
中国，杭州，（12）华西医院，成都，
中国（13）塘头医院，中国西安（14）
北京大学健康科学基础医学
中国北京中心（15）传染病学系
南方医科大学南方医院，（16）
上海市瑞金医院传染病科
交通大学医学院
背景：核苷（吨）后的响应耐久性
慢性乙型肝炎（CHB）停用类似药物（NAs）
不能令人满意这项研究的目的是确定
HBV DNA和HBV RNA作为预测指标的表现
方法：评估队列中包括130个
HBeAg阳性患者（30 8±6 9岁，男性72 3％）
来自一项多中心前瞻性试验，该试验终止了基于替比夫定的治疗
达到HBeAg血清转化和
HBV DNA <300拷贝/ mL> 48周并进行了随访
直到发生临床复发为止作为确认，40例患者
恩替卡韦治疗（36 5±9 4岁，男性72 5％）
或停药前的替诺福韦分析
治疗结束时（EOT）HBV DNA阴性
使用COBAS Taqman定义为“未检测到目标”
LLOD为20 IU / mL的检测方法。 HBV RNA阴性为
定义为在RT-qPCR中两个都没有靶向检测
不同的引物对主要的治疗后结果
被评估为临床复发，定义为HBV DNA>
2000 IU / mL加上ALT> 2×ULN。次要结果
包括病毒学复发定义为HBV DNA> 2000 IU /
毫升和HBeAg逆转定义为
两次连续的协议定义的访问中的HBeAg结果：
评估队列，四年的临床累积率
复发，病毒学复发和HBeAg逆转率为30 8％，
分别为54 7％和16 8％
具有双重阴性HBV DNA和RNA（DNA- / RNA-），
单阴性HBV DNA（DNA- / RNA +），单阴性HBV
RNA（DNA + / RNA-）和双阳性HBV DNA和RNA
（DNA + / RNA +）分别为19 7％（25/127），29 1％（37/127），6 3％
EOT患者（8/127）和44 9％（57/127）
“未检测到目标”的HBV DNA明显降低
临床复发的累积发生率
HBV DNA <20或> 20 IU / mL（20.0％vs. 39.8％vs. 40.0％，
P = 0.036）。同样，EOT HBV RNA阴性的患者
水平也显着降低了临床复发风险（15.3％
vs 37 0％，P = 0 029），在非治疗第4年时
回归分析表明，HBV DNA + RNA水平在
EOT（正向或负向两次）最强
临床复发的独立危险因素（危险比[HR]，
4.549； 95％置信区间[CI]，1.089-19.002，P = 0.038）
和病毒学复发（HR，11100; 95％CI，2690-45809;
P = 0 001），分别在第4年时EOT翻倍的患者
HBV DNA和RNA（DNA- / RNA-）阴性
与那些阳性者相比，其临床复发风险更低
HBV DNA或RNA（8.0％[2/25]对31.4％[32/102]，P = 0.018）。
在验证队列中，EOT HBV DNA- /
RNA-在直至
5.5年随访（15.4％[2/13]对33.3％[9/27]，P = 0.286）。
结论：HBV双阴性核酸（DNA- / RNA-）
在EOT中，具有更严格的定义是一种有效的生物标志物
指导CHB HBeAg阳性的NAs安全终止
耐心。