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J Hepatol
. 2022 Jan 26;S0168-8278(22)00020-4.
doi: 10.1016/j.jhep.2022.01.007. Online ahead of print.
Probability of HBsAg loss after nucleo(s)tide analogue withdrawal depends on HBV genotype and viral antigen levels
M J Sonneveld 1 , S-M Chiu 2 , J Y Park 3 , S M Brakenhoff 4 , A Kaewdech 5 , W K Seto 6 , Y Tanaka 7 , I Carey 8 , M Papatheodoridi 9 , F van Bömmel 10 , T Berg 11 , F Zoulim 12 , S H Ahn 13 , G N Dalekos 14 , N S Erler 15 , C Höner Zu Siederdissen 16 , H Wedemeyer 17 , M Cornberg 18 , M F Yuen 19 , K Agarwal 20 , A Boonstra 21 , M Buti 22 , T Piratvisuth 23 , G Papatheodoridis 24 , C-H Chen 25 , B Maasoumy 26 , CREATE study group
Affiliations
Affiliations
1
Departments of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: [email protected].
2
Internal Medicine, Koahsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. Electronic address: [email protected].
3
Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. Electronic address: [email protected].
4
Departments of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: [email protected].
5
Faculty of Medicine, Prince of Songkla University, Hatyai, Thailand. Electronic address: [email protected].
6
Department of Medicine, State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong. Electronic address: [email protected].
7
Department of Gastroenterology & Hepatology, Kumamoto University, Kumamoto, Japan. Electronic address: [email protected].
8
Institute of Liver Studies, King's College Hospital, London, United Kingdom. Electronic address: [email protected].
9
Department of Gastroenterology, "Laiko" General Hospital of Athens, National and Kapodistrian University of Athens, Greece. Electronic address: [email protected].
10
Division of Hepatology, Clinic for Oncology, Gastroenterology, Hepatology, Infectious Diseases and Pneumology, University Clinic Leipzig, Germany. Electronic address: [email protected].
11
Division of Hepatology, Clinic for Oncology, Gastroenterology, Hepatology, Infectious Diseases and Pneumology, University Clinic Leipzig, Germany. Electronic address: [email protected].
12
INSERM Unit 1052, Lyon, France. Electronic address: [email protected].
13
Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. Electronic address: [email protected].
14
Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece. Electronic address: [email protected].
15
Department of Biostatistics, Erasmus MC University Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: [email protected].
16
Department of Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany. Electronic address: [email protected].
17
Department of Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany. Electronic address: [email protected].
18
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: [email protected].
19
Department of Medicine, State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong. Electronic address: [email protected].
20
Institute of Liver Studies, King's College Hospital, London, United Kingdom. Electronic address: [email protected].
21
Departments of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: [email protected].
22
Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron and Ciberehd del Intituto Carlos III de Barcelona, Spain. Electronic address: [email protected].
23
Faculty of Medicine, Prince of Songkla University, Hatyai, Thailand. Electronic address: [email protected].
24
Department of Gastroenterology, "Laiko" General Hospital of Athens, National and Kapodistrian University of Athens, Greece. Electronic address: [email protected].
25
Internal Medicine, Koahsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. Electronic address: [email protected].
26
Department of Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany. Electronic address: [email protected].
PMID: 35092743 DOI: 10.1016/j.jhep.2022.01.007
Abstract
Background & aims: Nucleo(s)tide analogue (NUC) withdrawal may result in HBsAg clearance in a subset of patients, but predictors remain ill-defined.
Methods: We studied predictors of HBsAg loss after NUC withdrawal in a global cohort of HBeAg negative patients with undetectable HBV DNA who discontinued long-term NUC therapy. Patients requiring retreatment after therapy cessation were considered non-responders.
Results: We enrolled 1216 patients (991 with genotype data); 98 (8.1%) achieved HBsAg loss. The probability of HBsAg loss was higher in non-Asian patients (adjusted hazard ratio (aHR) 8.26, p<0.001), and in patients with lower HBsAg (aHR 0.243, p<0.001) and HBcrAg (aHR 0.718, p=0.001) levels. Combining HBsAg (<10, 10-100 or >100 IU/mL) and HBcrAg (<2log vs ≥2 log) levels improved prediction of HBsAg loss, with extremely low rates observed in patients with HBsAg >100 IU/mL with detectable HBcrAg. HBsAg loss rates also varied with HBV genotype; the highest rates were observed for genotypes A and D, and none of the patients with HBV genotype E experienced HBsAg loss (p<0.001 for the overall comparison across genotypes; p<0.001 for genotypes A/D versus genotypes B/C). HBV genotype C was independently associated with a higher probability of HBsAg loss when compared to genotype B among Asian patients (aHR 2.494, 95% CI: 1.490 - 4.174, p=0.001).
Conclusions: The probability of HBsAg loss after NUC cessation varies according to patient ethnicity, HBV genotype and end-of-treatment viral antigen levels. Patients with low HBsAg (<100 IU/ml) and/or undetectable HBcrAg levels, particularly if non-Asian or infected with HBV genotype C, appear to be the best candidates for therapy withdrawal.
Lay summary: A subset of patients may achieve clearance of HBsAg (so-called functional cure) after withdrawal of nucleo(s)tide analogue therapy. In this multicenter study of 1216 patients who discontinued antiviral therapy, we identified non-Asian ethnicity, HBV genotype C, and low hepatitis B surface antigen and hepatitis B core related antigen levels as factors associated with an increased chance of HBsAg loss.
Keywords: HBV genotype; HBcrAg; HBsAg; HBsAg loss.
Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved. |
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