一项国际队列研究恩替卡韦与富马酸替诺福韦二吡呋酯对慢

StephenW

一项国际队列研究恩替卡韦与富马酸替诺福韦二吡呋酯对慢性乙型肝炎功能性治愈的有效性
Yao-Chun Hsu 1 2 3 4 , Dae Won Jun 5 , Cheng-Yuan Peng 6 , Ming-Lun Yeh 7 8 , Huy Trinh 9 , Grace Lai-Hung Wong 10 , Sung Eun Kim 11 , Chien-Hung Chen 12 , Hyunwoo Oh 5 , Chia-Hsin Lin 6 , Lindsey Trinh 9 , Vincent Wai-Sun Wong 10 , Eilleen Yoon 5 13 , Sang Bong Ahn 14 , Daniel Huang 15 16 , Yong Kyun Cho 17 , Jae Yoon Jeong 18 , Soung Won Jeong 19 , Hyoung Su Kim 20 , Qing Xie 21 , Li Liu 22 , Mar Riveiro-Barciela 23 24 , Pei-Chien Tsai 7 , Elena Vargas Accarino 23 , Hidenori Toyoda 25 , Masaru Enomoto 26 , Carmen Preda 27 , Sebastián Marciano 28 , Joseph Hoang 29 , Chung-Feng Huang 7 , Ritsuzo Kozuka 26 , Satoshi Yasuda 25 , Doina Istratescu 27 , Dong-Hyun Lee 30 , Jia-Ying Su 31 , Yen-Tsung Huang 31 , Jee Fu Huang 7 , Chia-Yen Dai 7 , Wan- Long Chuang 7 , Man-Fung Yuen 32 , Adrian Gadano 28 , Ramsey Cheung 29 , Seng Gee Lim 15 16 , Maria Buti 23 , Ming-Lung Yu 7 , Mindie H Nguyen 33 34 35
隶属关系
隶属关系

    1
    台湾高雄义大医院/义守大学肝病中心及医学院。
    2
    台湾新北辅仁大学附属医院肠胃科。
    3
    国立阳明大学生物医学信息学研究所，新北，台湾。
    4
    中国医科大学临床医学科学研究生院，台中，台湾。
    5
    韩国首尔汉阳大学医学院汉阳大学医院内科。
    6
    台湾台中中华医科大学附属医院消化内科中心。
    7
    台湾高雄医科大学附属医院内科及肝炎中心肝胆科。
    8
    高雄医科大学医学院和肝炎研究中心、医学院、液体活检和队列研究中心，台湾高雄。
    9
    圣何塞胃肠病学，美国加利福尼亚州圣何塞。
    10
    香港中文大学医学与治疗学系，中国香港特别行政区。
    11
    韩国安阳市翰林大学医学院翰林大学圣心医院内科。
    12
    台湾高雄长庚纪念医院和长庚大学医学院内科。
    13
    韩国首尔仁济大学医学院白尚溪医院内科。
    14
    韩国首尔乙支大学医学院芦原乙支医疗中心内科。
    15
    新加坡国立大学医院胃肠病学和肝病学部。
    16
    新加坡国立大学杨潞龄医学院医学系，新加坡，新加坡。
    17
    韩国首尔成均馆大学医学院江北三星医院内科。
    18
    韩国九里，汉阳大学医学院，汉阳大学九里医院内科。
    19
    韩国首尔顺天乡大学医学院顺天乡大学医院内科。
    20
    韩国首尔翰林大学医学院韩东圣心医院内科。
    21
    【作者单位】： 上海交通大学医学院附属瑞金医院感染科;
    22
    【作者单位】： 昆明市第三医院感染科;
    23
    肝脏科，内科，Hospital Universitari Valle d'Hebron，Vall d'Hebron Barcelona Hospital Campus，Universitat Autònoma de Barcelona，西班牙巴塞罗那。
    24
    CIBERehd，卡洛斯三世研究所，马德里，西班牙。
    25
    日本大垣市立医院消化内科。
    26
    日本大阪市立大学医学研究生院肝病学系。
    27
    Institutul Clinic Fundeni-Gastroenterologie si Hepatologie，布加勒斯特，罗马尼亚。
    28
    阿根廷布宜诺斯艾利斯意大利布宜诺斯艾利斯医院肝病学和研究部。
    29
    美国加利福尼亚州帕洛阿尔托斯坦福大学医学中心医学系。
    30
    韩国釜山好江安医院消化内科。
    31
    台湾台北中央研究院统计科学研究所。
    32
    香港大学医学系，中国香港特别行政区。
    33
    美国加利福尼亚州帕洛阿尔托斯坦福大学医学中心医学系。 [email protected]。
34
    美国加利福尼亚州帕洛阿尔托市斯坦福大学医学中心流行病学和人口健康系。 [email protected]。
    35
    美国加利福尼亚州帕洛阿尔托斯坦福大学医学中心胃肠病学和肝病学部。 [email protected]。

    PMID：36070123 DOI：10.1007/s12072-022-10411-x

抽象的

简介：恩替卡韦 (ETV) 和富马酸替诺福韦酯 (TDF) 都是慢性乙型肝炎 (CHB) 的一线治疗药物，但它们在乙型肝炎表面抗原 (HBsAg) 血清清除方面的比较有效性仍不清楚。

方法：这项国际多中心队列研究从 10 个中心的 23 个中心招募了 7697 名初治 CHB 患者（中位年龄 50 岁；男性 66.75%），他们开始使用 ETV（n = 5430）或 TDF（n = 2267），基线没有恶性肿瘤或免疫抑制国家或地区。观察患者的 HBsAg 血清学清除直至死亡、失访或治疗中断或转换。 HBsAg 血清学清除的发生率根据竞争死亡率进行了调整，并在 ETV 和 TDF 队列之间进行了治疗加权逆概率 (IPTW) 以及多变量回归分析。

结果：研究人群的中位随访时间为 56.1 个月，观察了 36,929 人 11 人年。 HBsAg 血清学清除发生在 70 名 ETV 治疗和 21 名 TDF 治疗患者中，ETV 和 1.34% (95% CI 0.85-2.10%) 的 8 年累积发生率分别为 1.69% (95% CI 1.32-2.17) , 对于 TDF (p = 0.58)。在 IPTW 分析中，两个研究队列的背景协变量更加平衡，对于 HBsAg 血清清除率，TDF 与 ETV 的年龄调整风险比 (HR) 为 0.91（95% CI 0.50-1.64；p = 0.75）。此外，在多变量竞争风险回归模型中，两种药物之间没有显着差异（TDF 与 ETV 的调整亚分布 HR 0.92；95% CI 0.56-1.53​​；p = 0.76）。

结论：ETV 和 TDF 在 HBsAg 血清清除率方面没有显着差异，这两种方案都很少发生。

关键词：比较有效性；恩替卡韦；功能性治愈；乙型肝炎病毒;替诺福韦。

© 2022. 亚太肝脏研究协会。

StephenW

Effectiveness of entecavir vs tenofovir disoproxil fumarate for functional cure of chronic hepatitis B in an international cohort
Yao-Chun Hsu  1   2   3   4 , Dae Won Jun  5 , Cheng-Yuan Peng  6 , Ming-Lun Yeh  7   8 , Huy Trinh  9 , Grace Lai-Hung Wong  10 , Sung Eun Kim  11 , Chien-Hung Chen  12 , Hyunwoo Oh  5 , Chia-Hsin Lin  6 , Lindsey Trinh  9 , Vincent Wai-Sun Wong  10 , Eilleen Yoon  5   13 , Sang Bong Ahn  14 , Daniel Huang  15   16 , Yong Kyun Cho  17 , Jae Yoon Jeong  18 , Soung Won Jeong  19 , Hyoung Su Kim  20 , Qing Xie  21 , Li Liu  22 , Mar Riveiro-Barciela  23   24 , Pei-Chien Tsai  7 , Elena Vargas Accarino  23 , Hidenori Toyoda  25 , Masaru Enomoto  26 , Carmen Preda  27 , Sebastián Marciano  28 , Joseph Hoang  29 , Chung-Feng Huang  7 , Ritsuzo Kozuka  26 , Satoshi Yasuda  25 , Doina Istratescu  27 , Dong-Hyun Lee  30 , Jia-Ying Su  31 , Yen-Tsung Huang  31 , Jee Fu Huang  7 , Chia-Yen Dai  7 , Wan-Long Chuang  7 , Man-Fung Yuen  32 , Adrian Gadano  28 , Ramsey Cheung  29 , Seng Gee Lim  15   16 , Maria Buti  23 , Ming-Lung Yu  7 , Mindie H Nguyen  33   34   35
Affiliations
Affiliations

    1
    Center for Liver Diseases and School of Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.
    2
    Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan.
    3
    Institute of Biomedical Informatics, National Yang-Ming University, New Taipei, Taiwan.
    4
    Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
    5
    Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, South Korea.
    6
    Center for Digestive Medicine, China Medical University Hospital, Taichung, Taiwan.
    7
    Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
    8
    School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
    9
    San Jose Gastroenterology, San Jose, CA, USA.
    10
    Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.
    11
    Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea.
    12
    Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
    13
    Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, South Korea.
    14
    Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University College of Medicine, Seoul, South Korea.
    15
    Division of Gastroenterology and Hepatology, National University Hospital, Singapore, Singapore.
    16
    Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
    17
    Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
    18
    Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, South Korea.
    19
    Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, South Korea.
    20
    Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea.
    21
    Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
    22
    Department of Infection Disease, The Third Hospital of Kumming City, Kumming, China.
    23
    Liver Unit, Department of Internal Medicine, Hospital Universitari Valle d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain.
    24
    CIBERehd, Instituto Carlos III, Madrid, Spain.
    25
    Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan.
    26
    Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
    27
    Institutul Clinic Fundeni-Gastroenterologie si Hepatologie, Bucharest, Romania.
    28
    Hepatology and Department of Research, Hospital Italiano De Buenos Aires, Buenos Aires, Argentina.
    29
    Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA.
    30
    Department of Gastroenterology, Good Gang-An Hospital, Busan, South Korea.
    31
    Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
    32
    Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.
    33
    Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA. [email protected].
34
    Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA, USA. [email protected].
    35
    Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA. [email protected].

    PMID: 36070123 DOI: 10.1007/s12072-022-10411-x

Abstract

Introduction: Both entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first-line therapies for chronic hepatitis B (CHB), but their comparative effectiveness with regards to hepatitis B surface antigen (HBsAg) seroclearance remains unclear.

Methods: This international multicenter cohort study enrolled 7697 treatment-naïve CHB patients (median age 50 years; male 66.75%) initiated on either ETV (n = 5430) or TDF (n = 2267) without baseline malignancy or immunosuppression from 23 centers across 10 countries or regions. Patients were observed for HBsAg seroclearance until death, loss to follow-up, or treatment discontinuation or switching. The incidences of HBsAg seroclearance were adjusted for competing mortality and compared between ETV and TDF cohorts with inverse probability of treatment weighting (IPTW) and also by multivariable regression analysis.

Results: The study population was followed up for a median duration of 56.1 months with 36,929 11 person-years of observation. HBsAg seroclearance occurred in 70 ETV-treated and 21 TDF-treated patients, yielding 8-year cumulative incidence of 1.69% (95% confidence interval [CI] 1.32-2.17) for ETV and 1.34% (95% CI 0.85-2.10%), for TDF (p = 0.58). In the IPTW analysis with the two study cohorts more balanced in background covariates, the age-adjusted hazard ratio (HR) of TDF versus ETV for HBsAg seroclearance was 0.91 (95% CI 0.50-1.64; p = 0.75). Furthermore, there was no significant difference between the two medications in the multivariable competing risk regression model (adjusted sub-distributional HR 0.92 for TDF vs. ETV; 95% CI 0.56-1.53; p = 0.76).

Conclusions: ETV and TDF did not differ significantly in the incidence of HBsAg seroclearance, which rarely occurred with either regimen.

Keywords: Comparative effectiveness; Entecavir; Functional cure; Hepatitis B virus; Tenofovir.

© 2022. Asian Pacific Association for the Study of the Liver.