Gut. 2020;69(12):2214-2222.
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.
제1저자 김민석, 김승업, 신동현 · 교신저자 이정훈
소속 (19)
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
- Department of Internal Medicine and Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, South Korea.
- Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea.
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, South Korea.
- Department of Internal Medicine, Bucheon Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Bucheon, South Korea.
- Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea.
- Department of Internal Medicine, Konkuk University Hospital, Konkuk University School of Medicine, Seoul, South Korea.
- Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, South Korea.
- Department of Internal Medicine and Yonsei Liver Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
- Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, Catholic University of Korea, Incheon, South Korea.
- Department of Internal Medicine, Bucheon St. Mary's hospital, College of Medicine, Catholic University of Korea, Bucheon, South Korea.
- Department of Internal Medicine, Seoul Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, South Korea.
- Department of Inernal Medicine, Ewha Women's University College of Medicine, Seoul, South Korea.
- Cancer Research Centre of Lyon, INSERM U1052, Lyon University, Hospices Civils de Lyon, Lyon, France.
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea pindra@empal.com.
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.
© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
Keywords
HBV DNA redetectionHBsAgantiviralshepatocellular carcinoma
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.
그 밖의 정보
- 출판 형태
- Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
- 저널
- Gut · eISSN 1468-3288
- 전자 출판
- 2020-03-24
- MeSH
- Antiviral Agents / administration & dosage · Carcinoma, Hepatocellular / epidemiology / prevention & control / virology · DNA, Viral / blood · Female · Follow-Up Studies · Guanine / administration & dosage / analogs & derivatives · Hepatitis B Surface Antigens / blood · Hepatitis B virus / genetics · Hepatitis B, Chronic / drug therapy · Humans · Lamivudine / administration & dosage · Liver Neoplasms / epidemiology / prevention & control / virology · Male · Middle Aged · Sustained Virologic Response* · Tenofovir / administration & dosage
- Substances
- Antiviral Agents · DNA, Viral · Hepatitis B Surface Antigens · Lamivudine · entecavir · Guanine · Tenofovir