Off-Therapy Response After Nucleos(t)ide Analogue Withdrawal in Patients With Chronic Hepatitis B: An International, Multicenter, Multiethnic Cohort (RETRACT-B Study)

Grishma Hirode¹, Hannah S J Choi², Chien-Hung Chen³, Tung-Hung Su⁴, Wai-Kay Seto⁵, Stijn Van Hees⁶, Margarita Papatheodoridi⁷, Sabela Lens⁸, Grace Wong⁹, Sylvia M Brakenhoff¹⁰, Rong-Nan Chien¹¹, Jordan Feld¹, Milan J Sonneveld¹⁰, Henry L Y Chan⁹, Xavier Forns⁸, George V Papatheodoridis⁷, Thomas Vanwolleghem⁶, Man-Fung Yuen⁵, Yao-Chun Hsu¹², Jia-Horng Kao⁴, Markus Cornberg¹³, Bettina E Hansen¹⁴, Wen-Juei Jeng¹¹, Harry L A Janssen¹⁵; RETRACT-B Study Group

Affiliations

¹ Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; The Toronto Viral Hepatitis Care Network, Toronto, Canada.
² Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada.
³ Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
⁴ National Taiwan University Hospital, Taipei, Taiwan.
⁵ Department of Medicine and State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, Special administrative regions of China.
⁶ Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium.
⁷ Medical School of National and Kapodistrian University of Athens, Athens, Greece.
⁸ Hospital Clinic Barcelona, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain.
⁹ The Chinese University of Hong Kong, Hong Kong, Special administrative regions of China.
¹⁰ Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the 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, Kaohsiung, Taiwan.
¹³ Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany Centre for Individualized Infection Medicine, Hannover, Germany.
¹⁴ Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; The Toronto Viral Hepatitis Care Network, Toronto, Canada.
¹⁵ Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; The Toronto Viral Hepatitis Care Network, Toronto, Canada. Electronic address: harry.janssen@uhn.ca.

PMID: 34762906
DOI: 10.1053/j.gastro.2021.11.002

Multicenter Study

Off-Therapy Response After Nucleos(t)ide Analogue Withdrawal in Patients With Chronic Hepatitis B: An International, Multicenter, Multiethnic Cohort (RETRACT-B Study)

Grishma Hirode et al. Gastroenterology. 2022 Mar.

. 2022 Mar;162(3):757-771.e4.

doi: 10.1053/j.gastro.2021.11.002. Epub 2021 Nov 9.

Authors

Affiliations

¹ Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; The Toronto Viral Hepatitis Care Network, Toronto, Canada.
² Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada.
³ Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
⁴ National Taiwan University Hospital, Taipei, Taiwan.
⁵ Department of Medicine and State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, Special administrative regions of China.
⁶ Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium.
⁷ Medical School of National and Kapodistrian University of Athens, Athens, Greece.
⁸ Hospital Clinic Barcelona, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain.
⁹ The Chinese University of Hong Kong, Hong Kong, Special administrative regions of China.
¹⁰ Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the 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, Kaohsiung, Taiwan.
¹³ Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany Centre for Individualized Infection Medicine, Hannover, Germany.
¹⁴ Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; The Toronto Viral Hepatitis Care Network, Toronto, Canada.
¹⁵ Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; The Toronto Viral Hepatitis Care Network, Toronto, Canada. Electronic address: harry.janssen@uhn.ca.

PMID: 34762906
DOI: 10.1053/j.gastro.2021.11.002

Erratum in

Correction.
[No authors listed] [No authors listed] Gastroenterology. 2024 May;166(5):947. doi: 10.1053/j.gastro.2024.03.001. Epub 2024 Mar 15. Gastroenterology. 2024. PMID: 38493380 No abstract available.

Abstract

Background & aims: Functional cure, defined based on 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 after NA cessation in a large, international, multicenter, multiethnic cohort of patients with chronic hepatitis B (CHB).

Methods: This cohort study included patients with virally suppressed CHB who were hepatitis B e antigen (HBeAg)-negative and stopped NA therapy. Primary outcome was HBsAg loss after NA cessation, and secondary outcomes included virologic, biochemical, and clinical relapse, alanine aminotransferase flare, retreatment, and liver-related events after NA cessation.

Results: Among 1552 patients with CHB, 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 Whites (vs Asians: subdistribution hazard ratio, 6.8; 95% confidence interval, 2.7-16.8; P < .001) and among patients with HBsAg levels <100 IU/mL at end of therapy (vs ≥100 IU/mL: subdistribution hazard ratio, 22.5; 95% confidence interval, 13.1-38.7; P < .001). At 48 months of follow-up, Whites 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 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 hepatocellular carcinoma.

Conclusions: The best candidates for NA withdrawal are virally suppressed, HBeAg- negative, noncirrhotic patients with CHB with low HBsAg levels, particularly Whites with <1000 IU/mL and Asians with <100 IU/mL. However, strict surveillance is recommended to prevent deterioration.

Keywords: Antiviral; Discontinuation; HBV; HBsAg seroconversion.

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Comment in

Withdrawal of Nucleos(t)ide Analogues in the Treatment of Chronic Hepatitis B: A Cornelian Choice.
Pol S. Pol S. Gastroenterology. 2022 Mar;162(3):698-699. doi: 10.1053/j.gastro.2021.12.240. Epub 2021 Dec 14. Gastroenterology. 2022. PMID: 34914942 No abstract available.
A Road Less Traveled: To a Finite Chronic Hepatitis B Therapy.
Rathi S, Bhagat N, Singh V. Rathi S, et al. Gastroenterology. 2022 Sep;163(3):778-779. doi: 10.1053/j.gastro.2022.01.015. Epub 2022 Jan 14. Gastroenterology. 2022. PMID: 35038449 No abstract available.

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Off-Therapy Response After Nucleos(t)ide Analogue Withdrawal in Patients With Chronic Hepatitis B: An International, Multicenter, Multiethnic Cohort (RETRACT-B Study)

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Off-Therapy Response After Nucleos(t)ide Analogue Withdrawal in Patients With Chronic Hepatitis B: An International, Multicenter, Multiethnic Cohort (RETRACT-B Study)

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