AASLD2020[763]功能的发生率和因素 在ETV期间治愈（HBsAg清除）或

StephenW

763
INCIDENCE AND FACTORS ASSOCIATED WITH FUNCTIONAL
CURE (HBsAg SEROCLEARANCE) DURING ETV OR
TDF THERAPY FOR CHRONIC HEPATITIS B (CHB): AN
INTERNATIONAL REAL-WORLD STUDY WITH LONG-TERM
FOLLOW-UP
Yao-Chun Hsu1,2,3,4, Ming-Lun Yeh5, Grace Lai-Hung Wong6,
Chien Hung Chen7, Cheng-Yuan Peng8, Maria Asuncion Buti
Ferret9, Masaru Enomoto10, Qing Xie11, Huy N Trinh12, Carmen
Preda13, Li Liu14, Ka Shing Cheung15, Joseph Hoang16, Chung-
Feng Huang17, Mar Riveiro Barciela9, Ritsuzo Kozuka18,
Doina Istratescu13, Pei-Chien Tsai19, Elena Vargas-Accarino9,
Dong Hyun Lee20, Jee-Fu Huang21, Chia-Yen Dai17, Ramsey
Cheung22, Wan-Long Chuang23, Man-Fung Yuen15, Vincent
Wong24, Ming-Lung Yu17 and Mindie H. Nguyen22, (1)Center of
Liver Diseases, E-Da Hospital, (2)Fu-Jen Catholic University
Hospital, (3)Fu-Jen Catholic University, (4)China Medical
University, (5)Department of Internal Medicine, Kaohsiung
Medical University Hospital, (6)Department of Medicine and
Therapeutics, Medical Data Analytic Centre (MDAC), Institute
of Digestive Disease, The Chinese University of Hong
Kong, (7)Division of Hepatogastroenterology, Department
of Internal Medicine, Kaohsiung Chang Gung Memorial
Hospital, (8)Division of Hepatology and Gastroenterology,
Department of Internal Medicine, China Medical University
Hospital, (9)Hospital Universitari Vall d’Hebron and Ciberehd,
(10)Hepatology, Osaka City University Graduate School of
Medicine, (11)Shanghai Jiaotong University School of Medicine,
Ruijin Hospital, China, (12)San Jose Gastroenterology, (13)
Institutul Clinic Fundeni-Gastroenterologie Si Hepatologie,
(14)Hepatology, The Third Hospital of Kumming City, (15)
Medicine, The University of Hong Kong, (16)Division of
Gastroenterology and Hepatology, Stanford University
Medical Center, (17)Hepatobiliary Division, Department of
Internal Medicine, Kaohsiung Medical University Hospital,
Kaohsiung Medical University, Kaohsiung, Taiwan, (18)
Department of Hepatology, Osaka City University Graduate
School of Medicine, (19)Hepatobiliary Division, Department
of Internal Medicine, Kaohsiung Medical University Hospital,
Kaohsiung Medical University, (20)Gastroenterology, Good
Gang-an Hospital, (21)Faculty of Internal Medicine and
Hepatitis Research Center, College of Medicine, and Center
for Cohort Study, Kaohsiung Medical University, Kaohsiung,
Taiwan, (22)Division of Gastroenterology and Hepatology,
Department of Medicine, Stanford University Medical Center,
(23)Hepatobiliary Division, Department of Internal Medicine,
Kaohsiung Medical University Hospital, Kaohsiung, Taiwan,
(24)Department of Medicine and Therapeutics, the Chinese
University of Hong Kong, Hong Kong, China
Background: HBsAg seroclearance is often regarded as
the therapeutic endpoint for oral nucleos(t)ide analog (NA)
therapy for chronic hepatitis B (CHB), but long-term data from
patients treated with entecavir (ETV) or tenofovir disoproxil
fumarate (TDF) are limited We aimed to clarify the incidence
and determinants of HBsAg seroclearance during ETV or TDF
treatment Methods: This retrospective cohort study included
previously treatment-naïve adult CHB patients without
baseline malignancy from 13 centers from eight countries or
regions in the U.S., Europe, and Asia Pacific who initiated on
ETV or TDF monotherapy Patients were observed for HBsAg
seroclearance for up to 10 years, until death, loss to followup,
or March 01, 2020, whichever came first. We calculated
the incidence and explored the determinants of HBsAg
seroclearance using competing risk analysis adjusted for
mortality Results: The analysis included 5,188 patients with
a median age of 50 years (68 6% male, 85 7% Asian, 27 5%
HBeAg+, and 23 7% cirrhosis) During a median follow-up of
4 9 (IQR, 3 0--8 1) years, HBsAg clearance occurred in 67
patients yielding a 10-year cumulative incidence of 2 19%
(95% CI, 1 62--2 89%) and an average annual rate of 0 24%
(95% 0.19--0.31%) without significant change over time
(Table) On multivariable competing risk regression analysis,
the baseline factors independently associated with HBsAg
seroclearance included low level of serum HBV DNA <2,000 IU/
mL (adjusted sub-distribution HR [aSHR], 2 84; 95% CI, 1 65-
-4 87; P<0.001), acute flare with alanine aminotransferase
(ALT) >200 U/L (aSHR, 3.17; 95% CI, 1.76--5.72; P<0 001),
hyperbilirubinemia >2mg/dL (aSHR, 3.65; 95% CI, 1.87--
7 14; P<0 001), and presence of fatty liver on ultrasound
examination (aSHR, 2 17; 95% CI, 1 24--3 80; P=0 006)
Conclusion: HBsAg seroclearance rarely occurs in CHB
patients treated with ETV or TDF with an annual incidence
of 0 24% - a much lower rate than prior reported rates for
untreated patients of usually about 1%, and was associated
with low level viremia, ALT flare, hyperbilirubinemia, and fatty
liver. These findings indicate that HBsAg seroclearance is a
remote or even unrealistic endpoint of the current antiviral
strategy, while providing a realistic reference point for future
HBV cure clinical trial design.

StephenW

763
功能的发生率和因素
在ETV期间治愈（HBsAg清除）或
慢性乙型肝炎（CHB）的TDF治疗：AN
国际长期实物研究
跟进
许耀春1,2,3,4，叶明伦5，黄丽红6，
陈建宏7，彭成元8，玛丽亚·亚松森·布蒂
Ferret9，Enomoto Masaru10，Xie Xie，Huy N Trinh12，Carmen
Preda13，Li Liu14，Ka Shing Chang，Kashang Cheung15，Chung-
Feng Huang17，Mar Riveiro Barciela9，Ritsuzo Kozuka18，
Doina Istratescu13，Pei-Chien Tsai19，Elena Vargas-Accarino9，
李东H 20，黄洁夫21，戴家仁17，拉姆齐
张22，庄万龙23，袁文峰15，文森特
Wong24，余明龙17和Mindie H.Nguyen22，（1）
富仁天主教大学易大医院肝病（2）
医院，（3）辅仁大学，（4）中国医药
大学（5）高雄市内科
医科大学附属医院（6）
研究所医学数据分析中心（MDAC）治疗
香港中文大学消化系统疾病研究所
Kong，（7）肝肠胃科
高雄长庚纪念馆内科
医院，（8）肝病消化科，
中国医科大学附属内科
医院（9）希伯伦大学和西伯利亚大学，
（10）大阪市立大学大学院肝病学
医学（11）上海交通大学医学院，
中国瑞金医院，（12）圣何塞胃肠病学，（13）
肝病基础医学研究所
（14）昆明市第三医院肝病科，（15）
香港大学医学系（16）
斯坦福大学胃肠病学和肝病学
医学中心（17）肝胆科
高雄医科大学附属医院内科
台湾高雄市高雄医科大学（18）
大阪市立大学肝内科研究生
医学院（19）肝胆科
高雄医科大学附属医院内科
高雄医科大学，（20）胃肠病学，良好
港安医院（21）内科与内科
医学院肝炎研究中心和中心
高雄医科大学队列研究
台湾（22）胃肠病学和肝病科，
斯坦福大学医学中心医学系
（23）内科肝胆科
台湾高雄市高雄医科大学附属医院
（24）中国医药学系
香港大学，中国香港
背景：HBsAg血清清除通常被认为是
口服核苷酸类似物（NA）的治疗终点
治疗慢性乙型肝炎（CHB），但长期数据来自
恩替卡韦（ETV）或替诺福韦酯
富马酸酯（TDF）受限制我们旨在澄清发生率
ETV或TDF期间HBsAg血清清除率的决定因素
治疗方法：该回顾性队列研究包括
先前未接受过治疗的成人CHB患者
来自八个国家的13个中心的基线恶性肿瘤或
在美国，欧洲和亚太地区发起的
观察ETV或TDF单药治疗患者的HBsAg
血清清除长达10年，直到死亡，失去随访，
或2020年3月1日，以先到者为准。我们计算
HBsAg的发生率并探讨其决定因素
使用竞争风险分析调整血清清除率
死亡率结果：分析包括5,188例
中位年龄为50岁（男性为68 6％，亚洲为85 7％，亚洲为27 5％
HBeAg +和23 7％的肝硬化）
4 9（IQR，3 0--8 1）年，67发生了HBsAg清除
患者的10年累积发生率2 19％
（95％CI，1 62--2 89％），年平均率为0 24％
（95％0.19--0.31％）随时间变化不大
（表）在多变量竞争风险回归分析中，
与HBsAg独立相关的基线因素
血清清除包括低水平的血清HBV DNA <2,000 IU /
mL（调整后的子分布HR [aSHR]，2 84； 95％CI，1 65-
-4 87； P <0.001），急性发作时伴有丙氨酸转氨酶
（ALT）> 200 U / L（aSHR，3.17; 95％CI，1.76--5.72; P <0.001），
高胆红素血症> 2mg / dL（aSHR，3.65; 95％CI，1.87--
7 14; P <0 001），超声检查是否存在脂肪肝
检查（aSHR，2 17; 95％CI，1 24--3 80; P = 0 006）
结论：慢性乙型肝炎很少发生HBsAg血清清除
每年接受ETV或TDF治疗的患者
为0 24％-远低于先前报告的费率
未经治疗的患者通常约为1％，并且与
低水平病毒血症，ALT发作，高胆红素血症和脂肪
肝。这些发现表明HBsAg血清清除是一种
当前抗病毒药物的偏远甚至不切实际的终点
策略，同时为未来提供切合实际的参考点
HBV治愈的临床试验设计。