Stopping nucleot(s)ide analogues in non-cirrhotic HBeAg-negative chronic hepatitis B patients: HBsAg loss at 96 weeks is associated with low baseline HBsAg levels
Samuel A L Hall 1 2 , Gareth S Burns 1 2 , Despina Anagnostou 1 , Sara Vogrin 2 , Vijaya Sundararajan 2 3 , Dilip Ratnam 4 5 , Miriam T Levy 6 , John S Lubel 7 8 , Amanda J Nicoll 9 , Simone I Strasser 10 11 , William Sievert 4 5 , Paul V Desmond 1 , Meng C Ngu 12 , Peter Angus 13 14 , Marie Sinclair 13 , Christopher Meredith 15 , Gail Matthews 16 , Peter A Revill 17 , Kathy Jackson 17 , Margaret Littlejohn 17 , D Scott Bowden 17 , Stephen A Locarnini 17 , Kumar Visvanathan 1 2 , Alexander J Thompson 1 2
Affiliations
Affiliations
1
Gastroenterology Department of St Vincent's Hospital Melbourne, Melbourne, Australia.
2
Department of Infectious Disease and Immunology Research Centre, St Vincent's Hospital, Melbourne, Australia.
3
The Department of Public Health, La Trobe University, Melbourne, Australia.
4
Gastroenterology & Hepatology Unit, Monash Health, Melbourne, Australia.
5
Monash University, Melbourne, Australia.
6
Gastroenterology Department of Liverpool Hospital, Sydney, Australia.
7
Department of Gastroenterology, Alfred Health, Melbourne, Australia.
8
Central Clinical School, Monash University, The Alfred Centre, Melbourne, Australia.
9
Gastroenterology Department of Eastern Health, Melbourne, Australia.
10
AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia.
11
University of Sydney, Sydney, Australia.
12
Gastroenterology Department of Concord Repatriation General Hospital, Sydney, Australia.
13
Department of Gastroenterology & Hepatology, Austin Health, Melbourne, Australia.
14
University of Melbourne, Melbourne, Australia.
15
Gastroenterology Department of Bankstown-Lidcombe Hospital, Sydney, Australia.
16
Department of infectious Disease, St Vincent's Hospital Sydney, Sydney, Australia.
17
Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, The Doherty Institute, Melbourne, Australia.
PMID: 35521992 DOI: 10.1111/apt.16968
Abstract
Background and aims: Current guidelines recommend long-term nucleot(s)ide analogue (NA) therapy for patients with HBeAg-negative chronic hepatitis B (CHB). However, disease remission has been described after stopping NA therapy, as well as HBsAg loss.
Methods: We performed a prospective multi-centre cohort study of stopping NA therapy. Inclusion criteria were HBeAg-negative CHB, the absence of cirrhosis and HBVDNA<lower limit of quantification for ≥18 months. We assessed virological and biochemical outcomes including HBsAg loss, as well as NA restart rates, over 96 weeks.
Results: In total, 110 patients [62% entecavir (ETV); 28% tenofovir (TDF), 10% other] were enrolled. Median age was 56 years, 57% were male, 85% were Asian, median baseline HBsAg level was 705 (214-2325) IU/ml. Virological reactivation occurred in 109/110 patients, median time to detection was 8 (4-12) weeks, and occurred earlier after stopping TDF versus ETV (median 4 vs. 12 weeks p < 0.001). At week 96, 77 (70%) remained off-treatment, 65 (59%) had ALT <2× ULN, 31 (28%) patients were in disease remission with HBVDNA <2000 IU/ml plus ALT <2× ULN and 7 (6%) patients had lost HBsAg. Baseline HBsAg ≤10 IU/ml was associated with HBsAg loss (6/9 vs. 1/101 p < 0.001). ALT >5× ULN occurred in 35 (32%); ALT flares were not associated with HBsAg loss. There were no unexpected safety issues.
Conclusion: Virological reactivation was very common after stopping NA therapy and occurred earlier after stopping TDF versus ETV. The majority of patients had ALT <2× ULN at week 96, but only one-third achieved disease remission and HBsAg loss was rare. Very low HBsAg levels at baseline were uncommon but predicted for HBsAg loss and disease remission.
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