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.