Discontinuation of nucleos(t)ide analogues is not associated with a higher risk of HBsAg seroreversion after antiviral-induced HBsAg seroclearance: a nationwide multicentre study

Minseok Albert Kim¹, Seung Up Kim², Dong Hyun Sinn³, Jeong Won Jang⁴, Young-Suk Lim⁵, Sang Hoon Ahn², Jae-Jun Shim⁶, Yeon Seok Seo⁷, Yang Hyun Baek⁸, Sang Gyune Kim⁹, Young Seok Kim⁹, Ji Hoon Kim¹⁰, Won Hyeok Choe¹¹, Hyung Joon Yim¹², Hyun Woong Lee¹³, Jung Hyun Kwon¹⁴, Sung Won Lee¹⁵, Jae Young Jang¹⁶, Hwi Young Kim¹⁷, Yewan Park³, Gi-Ae Kim⁶, Hyun Yang⁴, Han Ah Lee⁷, Myeongseok Koh⁸, Young-Sun Lee¹⁰, Minkoo Kim¹², Young Chang¹⁶, Yoon Jun Kim¹, Jung-Hwan Yoon¹, Fabien Zoulim¹⁸, Jeong-Hoon Lee¹⁹

Affiliations

¹ Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
² Department of Internal Medicine and Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
³ Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
⁴ Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
⁵ Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
⁶ Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, South Korea.
⁷ Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea.
⁸ Department of Internal Medicine, Dong-A University College of Medicine, Busan, South Korea.
⁹ Department of Internal Medicine, Bucheon Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Bucheon, South Korea.
¹⁰ Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea.
¹¹ Department of Internal Medicine, Konkuk University Hospital, Konkuk University School of Medicine, Seoul, South Korea.
¹² Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, South Korea.
¹³ Department of Internal Medicine and Yonsei Liver Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
¹⁴ Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, Catholic University of Korea, Incheon, South Korea.
¹⁵ Department of Internal Medicine, Bucheon St. Mary's hospital, College of Medicine, Catholic University of Korea, Bucheon, South Korea.
¹⁶ Department of Internal Medicine, Seoul Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, South Korea.
¹⁷ Department of Inernal Medicine, Ewha Women's University College of Medicine, Seoul, South Korea.
¹⁸ Cancer Research Centre of Lyon, INSERM U1052, Lyon University, Hospices Civils de Lyon, Lyon, France.
¹⁹ Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea pindra@empal.com.

PMID: 32209606
DOI: 10.1136/gutjnl-2019-320015

Multicenter Study

Discontinuation of nucleos(t)ide analogues is not associated with a higher risk of HBsAg seroreversion after antiviral-induced HBsAg seroclearance: a nationwide multicentre study

Minseok Albert Kim et al. Gut. 2020 Dec.

. 2020 Dec;69(12):2214-2222.

doi: 10.1136/gutjnl-2019-320015. Epub 2020 Mar 24.

Authors

Affiliations

¹ Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
² Department of Internal Medicine and Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
³ Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
⁴ Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
⁵ Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
⁶ Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, South Korea.
⁷ Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea.
⁸ Department of Internal Medicine, Dong-A University College of Medicine, Busan, South Korea.
⁹ Department of Internal Medicine, Bucheon Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Bucheon, South Korea.
¹⁰ Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea.
¹¹ Department of Internal Medicine, Konkuk University Hospital, Konkuk University School of Medicine, Seoul, South Korea.
¹² Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, South Korea.
¹³ Department of Internal Medicine and Yonsei Liver Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
¹⁴ Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, Catholic University of Korea, Incheon, South Korea.
¹⁵ Department of Internal Medicine, Bucheon St. Mary's hospital, College of Medicine, Catholic University of Korea, Bucheon, South Korea.
¹⁶ Department of Internal Medicine, Seoul Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, South Korea.
¹⁷ Department of Inernal Medicine, Ewha Women's University College of Medicine, Seoul, South Korea.
¹⁸ Cancer Research Centre of Lyon, INSERM U1052, Lyon University, Hospices Civils de Lyon, Lyon, France.
¹⁹ Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea pindra@empal.com.

PMID: 32209606
DOI: 10.1136/gutjnl-2019-320015

Abstract

Objective: Direct comparison of the clinical outcomes between nucleos(t)ide analogue (NA) discontinuation versus NA continuation has not been performed in patients with chronic hepatitis B who achieved HBsAg-seroclearance. Whether NA discontinuation was as safe as NA continuation after NA-induced surface antigen of HBV (HBsAg) seroclearance was investigated in the present study.

Designs: This multicentre study included 276 patients from 16 hospitals in Korea who achieved NA-induced HBsAg seroclearance: 131 (47.5%) discontinued NA treatment within 6 months after HBsAg seroclearance (NA discontinuation group) and 145 (52.5%) continued NA treatment (NA continuation group). Primary endpoint was HBsAg reversion and secondary endpoints included serum HBV DNA redetection and development of hepatocellular carcinoma (HCC).

Results: During follow-up (median=26.9 months, IQR=12.2-49.2 months), 10 patients (3.6%) experienced HBsAg reversion, 6 (2.2%) showed HBV DNA redetection and 8 (2.9%) developed HCC. Compared with NA continuation, NA discontinuation was not associated with HBsAg reversion in both univariable (HR=0.45, 95% CI=0.12 to 1.76, log-rank p=0.24) and multivariable analyses (adjusted HR=0.65, 95% CI=0.16 to 2.59, p=0.54). The cumulative probabilities of HBsAg reversion at 1, 3 and 5 years were 0.8%, 2.3% and 5.0% in the NA discontinuation group, and 1.5%, 6.3% and 8.4% in the NA continuation group, respectively. NA discontinuation was not associated with higher risk of either HBV redetection (HR=0.83, 95% CI=0.16 to 4.16, log-rank p=0.82) or HCC development (HR=0.53, 95% CI=0.12 to 2.23, log-rank p=0.38).

Conclusion: The discontinuation of NA was not associated with a higher risk of either HBsAg reversion, serum HBV DNA redetection or HCC development compared with NA continuation among patients who achieved HBsAg seroclearance with NA.

Keywords: HBV DNA redetection; HBsAg; antivirals; hepatocellular carcinoma.

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Conflict of interest statement

Competing interests: SUK reports receiving grants from Yuhan Pharmaceuticals, and lecture fees from Bristol-Myers Squibb, Gilead Science and Yuhan Pharmaceuticals; JWJ reports receiving research grants from Yuhan Pharmaceuticals and lecture fees from Abbie, Bristol-Myers Squibb, Gilead Science and MSD Korea, and serving as an advisory board member of Abbie, Gilead Science and MSD Korea; Y-SL reports receiving research grants from Bayer HealthCare Pharmaceuticals and Gilead Science, and serving as an advisory board member of Bayer HealthCare Pharmaceuticals and Gilead Science; HWL reports receiving lecture fee from Abbie, Chongkundang Pharmaceuticals, Dong-A ST Pharmaceuticals, Ildong Pharmaceuticals and Yuhan Pharmaceuticals; JHK, lecture fee from Abbie, Bristol-Myers Squibb, Gilead Science, and MSD Korea; SWL reports receiving research grants from Yuhan Pharmaceuticals, lecture fees from Abbie, Bristol-Myers Squibb, Bukwang Pharmaceuticals, Daewoong Pharmaceuticals, MSD Korea and Yuhan Pharmaceuticals, and serving as an advisory board member of Eisai and Gilead Science; JYJ reports receiving research grants from Bukwang and Yuhan Pharmaceuticals, lecture fees from Bristol-Myers Squibb, Bukwang Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Celltrion, Daewoong Pharmaceuticals, Gilead Science and Yuhan Pharmaceuticals; YJK reports receiving research grants from Bristol-Myers Squibb, Roche, JW Creagene, Bukwang Pharmaceuticals, Handok Pharmaceuticals, Hanmi Pharmaceuticals, Yuhan Pharmaceuticals and Pharmaking, and lecture fees from Bayer HealthCare Pharmaceuticals, Gilead Science, MSD Korea, Yuhan Pharmaceuticals, Samil Pharmaceuticals, CJ Pharmaceuticals, Bukwang Pharmaceuticals and Handok Pharmaceuticals; J-HY reports receiving research grant from Bayer HealthCare Pharmaceuticals, Bukwang Pharmaceuticals and Daewoong Pharmaceuticals, and J-HL reports receiving lecture fees from GreenCross Cell, Daewoong Pharmaceuticals and Gilead Korea.

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Discontinuation of nucleos(t)ide analogues is not associated with a higher risk of HBsAg seroreversion after antiviral-induced HBsAg seroclearance: a nationwide multicentre study

Affiliations

Discontinuation of nucleos(t)ide analogues is not associated with a higher risk of HBsAg seroreversion after antiviral-induced HBsAg seroclearance: a nationwide multicentre study

Authors

Affiliations

Abstract

Conflict of interest statement

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