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.
Bibliographical noteFunding 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).
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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- HBV DNA redetection
- hepatocellular carcinoma