Article Text

Download PDFPDF
Average corticosteroid dose and risk for HBV reactivation and hepatitis flare in patients with resolved hepatitis B infection
  1. Zhenyu Zhong,
  2. Weiting Liao,
  3. Lingyu Dai,
  4. Xiaojie Feng,
  5. Guannan Su,
  6. Yu Gao,
  7. Qiuying Wu,
  8. Peizeng Yang
  1. The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, and Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China
  1. Correspondence to Dr Peizeng Yang, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China; peizengycmu{at}


Objectives Corticosteroids remain the mainstay of treatment for rheumatic diseases but can cause hepatitis B virus (HBV) reactivation in patients with resolved HBV infection. Risk assessment and stratification are needed to guide the management of these patients before corticosteroid therapy.

Methods We prospectively enrolled patients with negative hepatitis B surface antigen positive Anti-hepatitis B core status with or without corticosteroid use and determined corticosteroid exposure by calculating cumulative dose and time-weighted average daily dose of prednisone. The primary outcome was the time to a composite of HBV reactivation, hepatitis flare or severe hepatitis.

Results Among 1303 participants, the median of cumulative dose and time-weighted average dose of prednisone used in this cohort was 3000 mg (IQR: 300–6750 mg) and 15 mg/day (IQR: 10–20 mg/day), respectively. In multivariable analyses, cumulative dose showed inverted V-shaped relationship with primary events, which peaked at a cumulative dose of 1506 mg (HR: 3.72; 95% CI, 1.96 to 7.08). Quartiles of time-weighted average dose were independently associated with a monotonic increase in event risk (HR per quartile increase: 2.15; 95% CI, 1.56 to 2.98), reaching an HR of 49.48 (95% CI, 6.24 to 392.48) in the top quartile. The incidence of primary outcome was 16.67 per 100 person-years in the top quartile of time-weighted average dose (Q4>20 mg/day). Other quartiles all had an incidence of primary outcome less than 10 per 100 person-years.

Conclusion Patients with time-weighted average prednisone dose greater than 20 mg/day would be classified as the high risk for HBV reactivation or hepatitis flare. Prophylactic Anti-HBV therapy may be needed for these high-risk patients.

Trial registration number ChiCTR1900023955.

  • corticosteroids
  • autoimmune diseases
  • immune system diseases
  • inflammation
  • glucocorticoids

Data availability statement

No data are available.

Statistics from


  • ZZ and WL are joint first authors.

  • Handling editor Josef S Smolen

  • Contributors ZZ designed the study. PY supervised the study. WL, LD, XF, GS, YG and QW collected clinical data. ZZ and WL analysed and interpreted the data. ZZ wrote the first draft of the paper. PY, ZZ and WL reviewed and edited the manuscript. PY served as the overall content guarantor. All authors provided a final review and approved the manuscript before submission.

  • Funding The work was supported by National Natural Science Foundation Key Program (81930023), Natural Science Foundation Major International (Regional) Joint Research Project (81720108009), Chongqing Key Laboratory of Ophthalmology (2008CA5003), Chongqing Outstanding Scientists Project (2019), Chongqing Chief Medical Scientist Project (2018) and Chongqing Science and Technology Platform and Base Construction Program (cstc2014pt-sy10002).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.