Digestive Diseases and Sciences

, Volume 64, Issue 10, pp 2992–3000 | Cite as

Early Hepatitis B Surface Antigen Seroclearance Following Antiviral Treatment in Patients with Reactivation of Resolved Hepatitis B

  • Hae Lim Lee
  • Jeong Won JangEmail author
  • Ji Won Han
  • Sung Won Lee
  • Si Hyun Bae
  • Jong Young Choi
  • Nam Ik Han
  • Seung Kew Yoon
  • Hee-Je Kim
  • Seok Lee
  • Seok-Goo Cho
  • Chang-Ki Min
  • Dong-Wook Kim
  • Jong Wook Lee
Original Article


Background and Aims

Long-term results on hepatitis B virus (HBV) reactivation in patients with resolved infection during anti-cancer therapy are unknown. This study investigated long-term risk and therapeutic endpoints including hepatitis B surface antigen (HBsAg) seroclearance following antiviral therapy in patients developing reactivation of resolved HBV.


The study included 528 consecutive HBsAg-negative/hepatitis B core antibody-positive patients who underwent rituximab treatment or hematopoietic stem cell transplantation (HSCT) between 2006 and 2016. Long-term outcomes of patients with reactivation after antiviral therapy were examined in comparison with 37 HBsAg-positive chronic carriers under the same medical settings.


The 7-year cumulative rate of HBV reactivation was 10.8% and 57.9% in patients receiving rituximab treatment and HSCT, respectively. After antiviral initiation, patients with reactivation of resolved HBV showed significantly higher 1-year cumulative rates of hepatitis B e antigen seroconversion (69.2% vs. 22.6%, P = 0.008) and HBsAg seroclearance (61.8% vs. 3.3%, P < 0.001) than chronic HBsAg carriers. Reactivation of resolved HBV was independently predictive of HBsAg seroclearance in a combined group of reactivated patients and chronic HBsAg carriers. Low viral load at reactivation was predictive of HBsAg seroclearance in reactivated patients. The majority of patients with HBsAg seroclearance developed anti-HBs. None of the reactivated patients who achieved HBsAg seroclearance relapsed after cessation of antiviral therapy.


HBsAg seroclearance rapidly occurs following antiviral therapy for reactivation of resolved HBV infection, suggesting distinct clinical phenotypes as well as shorter duration of HBV infection associated with this particular disease setting-HBV reactivation.


HBV reactivation Resolved hepatitis B HBsAg seroclearance Antiviral therapy 



This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2016R1D1A1B03930457). Study sponsor has no role in study design, in the collection, analysis and interpretation of data.

Author’s contribution

JWJ and HLL were involved in study concept and design, collecting and interpreting data, JWJ, HLL, JWH, SWL, SHB, JYC, NIH, SKY, H-JK, SL, S-GC, C-KM, D-WK and JWL contributed to reagents/materials/analysis tools, and JWJ and HLL wrote the paper. All authors have approved this final version of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no financial conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Hae Lim Lee
    • 1
  • Jeong Won Jang
    • 1
    Email author
  • Ji Won Han
    • 3
  • Sung Won Lee
    • 1
  • Si Hyun Bae
    • 1
  • Jong Young Choi
    • 1
  • Nam Ik Han
    • 1
  • Seung Kew Yoon
    • 1
  • Hee-Je Kim
    • 2
  • Seok Lee
    • 2
  • Seok-Goo Cho
    • 2
  • Chang-Ki Min
    • 2
  • Dong-Wook Kim
    • 2
  • Jong Wook Lee
    • 2
  1. 1.Division of Hepatology, Department of Internal Medicine, College of MedicineThe Catholic University of KoreaSeoulRepublic of Korea
  2. 2.Division of Hematology, Department of Internal Medicine, College of MedicineThe Catholic University of KoreaSeoulRepublic of Korea
  3. 3.Laboratory of Translational Immunology and VaccinologyGraduate School of Medical Science and Engineering, KAISTDaejeonRepublic of Korea

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