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; Seung Up Kim; Dong Hyun Sinn; Jeong Won Jang; Young Suk Lim; Sang Hoon Ahn; Jae Jun Shim; Yeon Seok Seo; Yang Hyun Baek; Sang Gyune Kim; Young Seok Kim; Ji Hoon Kim; Won Hyeok Choe; Hyung Joon Yim; Hyun Woong Lee; Jung Hyun Kwon; Sung Won Lee; Jae Young Jang; Hwi Young Kim; Yewan Park; Gi Ae Kim; Hyun Yang; Han Ah Lee; Myeongseok Koh; Young Sun Lee; Minkoo Kim; Young Chang; Yoon Jun Kim; Jung Hwan Yoon; Fabien Zoulim; Jeong Hoon Lee

doi:10.1136/gutjnl-2019-320015

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, Seung Up Kim, Dong Hyun Sinn, Jeong Won Jang, Young Suk Lim, Sang Hoon Ahn, Jae Jun Shim, Yeon Seok Seo, Yang Hyun Baek, Sang Gyune Kim, Young Seok Kim, Ji Hoon Kim, Won Hyeok Choe, Hyung Joon Yim, Hyun Woong Lee, Jung Hyun Kwon, Sung Won Lee, Jae Young Jang, Hwi Young Kim, Yewan ParkGi Ae Kim, Hyun Yang, Han Ah Lee, Myeongseok Koh, Young Sun Lee, Minkoo Kim, Young Chang, Yoon Jun Kim, Jung Hwan Yoon, Fabien Zoulim, Jeong Hoon Lee

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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.

Original language	English
Pages (from-to)	2214-2222
Number of pages	9
Journal	Gut
Volume	69
Issue number	12
DOIs	https://doi.org/10.1136/gutjnl-2019-320015
State	Published - 1 Dec 2020

Bibliographical note

Funding Information:
Funding The trial was supported by grants from liver research Foundation of Korea as part of Bio Future strategies research Project, seoul national University hospital research Fund (grant number 03-2016-0380), and from the national research Foundation of Korea (nrF) grants funded by the Korea government (MsiP) (grant number nrF-2019r1a2c2010311).

Funding Information:
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.

Publisher Copyright:
© 2020 BMJ Publishing Group. All rights reserved.

Keywords

HBV DNA redetection
HBsAg
antivirals
hepatocellular carcinoma

Access to Document

10.1136/gutjnl-2019-320015

Cite this

Kim, M. A., Kim, S. U., Sinn, D. H., Jang, J. W., Lim, Y. S., Ahn, S. H., Shim, J. J., Seo, Y. S., Baek, Y. H., Kim, S. G., Kim, Y. S., Kim, J. H., Choe, W. H., Yim, H. J., Lee, H. W., Kwon, J. H., Lee, S. W., Jang, J. Y., Kim, H. Y., ... Lee, J. H. (2020). 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. Gut, 69(12), 2214-2222. https://doi.org/10.1136/gutjnl-2019-320015

@article{c6de1ed34905490c86d7d9f2beab983d,

title = "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",

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",

author = "Kim, {Minseok Albert} and Kim, {Seung Up} and Sinn, {Dong Hyun} and Jang, {Jeong Won} and Lim, {Young Suk} and Ahn, {Sang Hoon} and Shim, {Jae Jun} and Seo, {Yeon Seok} and Baek, {Yang Hyun} and Kim, {Sang Gyune} and Kim, {Young Seok} and Kim, {Ji Hoon} and Choe, {Won Hyeok} and Yim, {Hyung Joon} and Lee, {Hyun Woong} and Kwon, {Jung Hyun} and Lee, {Sung Won} and Jang, {Jae Young} and Kim, {Hwi Young} and Yewan Park and Kim, {Gi Ae} and Hyun Yang and Lee, {Han Ah} and Myeongseok Koh and Lee, {Young Sun} and Minkoo Kim and Young Chang and Kim, {Yoon Jun} and Yoon, {Jung Hwan} and Fabien Zoulim and Lee, {Jeong Hoon}",

note = "Funding Information: Funding The trial was supported by grants from liver research Foundation of Korea as part of Bio Future strategies research Project, seoul national University hospital research Fund (grant number 03-2016-0380), and from the national research Foundation of Korea (nrF) grants funded by the Korea government (MsiP) (grant number nrF-2019r1a2c2010311). Funding Information: 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. Publisher Copyright: {\textcopyright} 2020 BMJ Publishing Group. All rights reserved.",

year = "2020",

month = dec,

day = "1",

doi = "10.1136/gutjnl-2019-320015",

language = "English",

volume = "69",

pages = "2214--2222",

journal = "Gut",

issn = "0017-5749",

publisher = "BMJ Publishing Group",

number = "12",

}

Kim, MA, Kim, SU, Sinn, DH, Jang, JW, Lim, YS, Ahn, SH, Shim, JJ, Seo, YS, Baek, YH, Kim, SG, Kim, YS, Kim, JH, Choe, WH, Yim, HJ, Lee, HW, Kwon, JH, Lee, SW, Jang, JY, Kim, HY, Park, Y, Kim, GA, Yang, H, Lee, HA, Koh, M, Lee, YS, Kim, M, Chang, Y, Kim, YJ, Yoon, JH, Zoulim, F & Lee, JH 2020, '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', Gut, vol. 69, no. 12, pp. 2214-2222. https://doi.org/10.1136/gutjnl-2019-320015

TY - JOUR

T1 - Discontinuation of nucleos(t)ide analogues is not associated with a higher risk of HBsAg seroreversion after antiviral-induced HBsAg seroclearance

T2 - A nationwide multicentre study

AU - Kim, Minseok Albert

AU - Kim, Seung Up

AU - Sinn, Dong Hyun

AU - Jang, Jeong Won

AU - Lim, Young Suk

AU - Ahn, Sang Hoon

AU - Shim, Jae Jun

AU - Seo, Yeon Seok

AU - Baek, Yang Hyun

AU - Kim, Sang Gyune

AU - Kim, Young Seok

AU - Kim, Ji Hoon

AU - Choe, Won Hyeok

AU - Yim, Hyung Joon

AU - Lee, Hyun Woong

AU - Kwon, Jung Hyun

AU - Lee, Sung Won

AU - Jang, Jae Young

AU - Kim, Hwi Young

AU - Park, Yewan

AU - Kim, Gi Ae

AU - Yang, Hyun

AU - Lee, Han Ah

AU - Koh, Myeongseok

AU - Lee, Young Sun

AU - Kim, Minkoo

AU - Chang, Young

AU - Kim, Yoon Jun

AU - Yoon, Jung Hwan

AU - Zoulim, Fabien

AU - Lee, Jeong Hoon

N1 - Funding Information: Funding The trial was supported by grants from liver research Foundation of Korea as part of Bio Future strategies research Project, seoul national University hospital research Fund (grant number 03-2016-0380), and from the national research Foundation of Korea (nrF) grants funded by the Korea government (MsiP) (grant number nrF-2019r1a2c2010311). Funding Information: 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. Publisher Copyright: © 2020 BMJ Publishing Group. All rights reserved.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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.

AB - 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.

KW - HBV DNA redetection

KW - HBsAg

KW - antivirals

KW - hepatocellular carcinoma

UR - http://www.scopus.com/inward/record.url?scp=85082521120&partnerID=8YFLogxK

U2 - 10.1136/gutjnl-2019-320015

DO - 10.1136/gutjnl-2019-320015

M3 - Article

C2 - 32209606

AN - SCOPUS:85082521120

SN - 0017-5749

VL - 69

SP - 2214

EP - 2222

JO - Gut

JF - Gut

IS - 12

ER -

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

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this