Off-therapy response after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B: An international, multi-center, multi-ethnic cohort (RETRACT-B study)
Grishma Hirode 1 , Hannah Sj Choi 2 , Chien-Hung Chen 3 , Tung-Hung Su 4 , Wai-Kay Seto 5 , Stijn Van Hees 6 , Margarita Papatheodoridi 7 , Sabela Lens 8 , Grace Wong 9 , Sylvia M Brakenhoff 10 , Rong-Nan Chien 11 , Jordan Feld 1 , Milan Sonneveld 10 , Henry Ly Chan 9 , Xavier Forns 8 , George V Papatheodoridis 7 , Thomas Vanwolleghem 6 , Man-Fung Yuen 5 , Yao-Chun Hsu 12 , Jia-Horng Kao 4 , Markus Cornberg 13 , Bettina E Hansen 14 , Wen-Juei Jeng 11 , Harry LA Janssen 15 , RETRACT-B study group
Affiliations
Affiliations
1
Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Canada; Institute of Medical Science, University of Toronto, Canada; The Toronto Viral Hepatitis Care Network (VIRCAN), Canada.
2
Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Canada; Institute of Medical Science, University of Toronto, Canada.
3
Kaohsiung Chang Gung Memorial Hospital, Taiwan.
4
National Taiwan University Hospital, Taiwan.
5
Department of Medicine and State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, SAR, China.
6
Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium.
7
Medical School of National and Kapodistrian University of Athens, Greece.
8
Hospital Clinic Barcelona, IDIBAPS and CIBEREHD, University of Barcelona, Spain.
9
The Chinese University of Hong Kong, Hong Kong, SAR, China.
10
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands.
11
Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University, Linkou, Taiwan.
12
E-Da Hospital/I-Shou University, Taiwan, Taiwan.
13
Department of Gastroenterology, Hepatolology and Endocrinology, Hannover Medical School, Germany; Centre for Individualized Infection Medicine (CiiM), Hannover, Germany.
14
Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Canada; The Toronto Viral Hepatitis Care Network (VIRCAN), Canada.
15
Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Canada; Institute of Medical Science, University of Toronto, Canada; The Toronto Viral Hepatitis Care Network (VIRCAN), Canada. Electronic address: [email protected].
PMID: 34762906 DOI: 10.1053/j.gastro.2021.11.002
Abstract
Background and aims: Functional cure, defined by hepatitis B surface antigen (HBsAg) loss, is rare during nucleos(t)ide analogue (NA) therapy and guidelines on finite NA therapy have not been well established. We aim to analyze off-therapy outcomes following NA cessation in a large, international, multi-center, multi-ethnic cohort of chronic hepatitis B (CHB) patients.
Methods: This cohort study included virally suppressed CHB patients who were hepatitis B e antigen (HBeAg) negative and stopped NA therapy. Primary outcome was HBsAg loss after NA cessation, and secondary outcomes included virological, biochemical, and clinical relapse, ALT flare, retreatment, and liver-related events after NA cessation.
Results: Among 1,552 CHB patients, cumulative probability of HBsAg loss was 3.2% at 12 months and 13.0% at 48 months of follow-up. HBsAg loss was higher among Caucasians (vs. Asians: SHR 6.8; 95% CI 2.7-16.8; P < .001), and among patients with HBsAg levels <100 IU/mL at end of therapy (vs. ≥100 IU/mL: SHR 22.5; 95% CI 13.1-38.7; P < .001). At 48 months of follow-up, Caucasians with HBsAg levels <1000 IU/mL and Asians with HBsAg levels <100 IU/mL at end of therapy had a high predicted probability of HBsAg loss (>30%). Incidence rate of hepatic decompensation and hepatocellular carcinoma (HCC) was 0.48 per 1000 person-years and 0.29 per 1000 person-years, respectively. Death occurred in 7/19 decompensated patients and 2/14 patients with HCC.
Conclusion: The best candidates for NA withdrawal are virally suppressed, HBeAg negative, non-cirrhotic CHB patients with low HBsAg levels, particularly Caucasians with <1000 IU/mL and Asians with <100 IU/mL. However, strict surveillance is recommended to prevent deterioration.