International Journal of Clinical Pharmacy

, Volume 40, Issue 1, pp 169–174 | Cite as

The prevalence and risk factors of hepatitis B flares in chronic hepatitis B patients receiving glucocorticoid pulse therapy

  • Ying-Cheng Lin
  • Shou-Wu Lee
  • Hong-Zen Yeh
  • Chi-Sen Chang
  • Sheng-Shun YangEmail author
Research Article


Background The frequency and risks of hepatitis B reactivation in patients receiving glucocorticoid pulse therapy has not been reported. Objective The aim of our study was to investigate the possibility of glucocorticoid pulse therapy related hepatitis B flare. Setting A Taiwanese tertiary hospital. Methods Chronic hepatitis B patients underwent glucocorticoid pulse therapy were retrospectively collected. The prevalence of hepatitis B flare was counted, and the statistic analysis with logistic regression was adapted to assess the associated risk factors. Main outcome measure The prevalence and associated risk factors of the individuals with hepatitis B flare after glucocorticoid pulse therapy were collected and analyzed. Results A total of 112 patients were identified. Forty patients had received prophylactic antiviral therapy and none of them developed hepatitis B flare. Among the 72 patients who had not received antiviral prophylaxis, 11 of them (15.3%) experienced hepatitis B flares. Those individuals with hepatitis B flares, comparing to those without, were younger (37.4 ± 13.3 vs. 46.0 ± 11.1, p = 0.038), had higher ratio of HBeAg positivity (50 vs. 15.9%, p = 0.017), higher percentage of high hepatitis B viral load (81.8 vs. 8.3%, p = 0.002), higher maintenance glucocorticoid dose (prednisone or equivalent 22.7 ± 14.9 vs. 10.7 ± 12.4 mg, p = 0.003) and higher ratio of cyclophosphamide use (27.3 vs. 1.6%, p = 0.010). After multivariate analysis, only higher dose of maintenance glucocorticoid was related to hepatitis B flare (odds ratio, 1.08; 95% CI, 1.01–1.16). Conclusion A higher maintenance glucocorticoid dosage is associated with the risk of hepatitis B flare after glucocorticoid pulse therapy. No hepatitis B flare occurred in patients receiving prophylactic antiviral therapy before glucocorticoid pulse therapy.


Glucocorticoid pulse therapy HBV Hepatitis B flare Immunosuppressive therapy 



The authors would like to thank the support from Clinical Informatics Research and Development Center of Taichung Veterans General Hospital.


This project received no special funding.

Conflicts of interest

The authors declare that there are no conflicts of interest.

Supplementary material

11096_2017_584_MOESM1_ESM.pdf (92 kb)
Supplementary material 1 (PDF 91 kb)
11096_2017_584_MOESM2_ESM.pdf (118 kb)
Supplementary material 2 (PDF 117 kb)


  1. 1.
    Chang ML, Liaw YF. Hepatitis B flares in chronic hepatitis B: pathogenesis, natural course, and management. J Hepatol. 2014;61:1407–17.CrossRefPubMedGoogle Scholar
  2. 2.
    Liaw YF, Chu CM. Hepatitis B virus infection. Lancet. 2009;373:582–92.CrossRefPubMedGoogle Scholar
  3. 3.
    Lam KC, Lai CL, Trepo C, Wu PC. Deleterious effect of prednisolone in HBsAg-positive chronic active hepatitis. N Engl J Med. 1981;304:380–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Perrillo RP. Acute flares in chronic hepatitis B: the natural and unnatural history of an immunologically mediated liver disease. Gastroenterology. 2001;120:1009–22.CrossRefPubMedGoogle Scholar
  5. 5.
    Cheng AL, Hsiung CA, Su IJ, Chen PJ, Chang MC, Tsao CJ, et al. Steroid-free chemotherapy decreases risk of hepatitis B virus (HBV) reactivation in HBV-carriers with lymphoma. Hepatology. 2003;37:1320–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Lan JL, Chen YM, Hsieh TY, Chen YH, Hsieh CW, Chen DY, et al. Kinetics of viral loads and risk of hepatitis B virus reactivation in hepatitis B core antibody-positive rheumatoid arthritis patients undergoing anti-tumour necrosis factor alpha therapy. Ann Rheum Dis. 2011;70:1719–25.CrossRefPubMedGoogle Scholar
  7. 7.
    Reddy KR, Beavers KL, Hammond SP, Lim JK, Falck-Ytter YT, American Gastroenterological Association I. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148:215–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Schalm SW, Summerskill WH, Gitnick GL, Elveback LR. Contrasting features and responses to treatment of severe chronic active liver disease with and without hepatitis BS antigen. Gut. 1976;17:781–6.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10:1–98.CrossRefPubMedGoogle Scholar
  10. 10.
    Perrillo RP, Gish R, Falck-Ytter YT. American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148:221–44.CrossRefPubMedGoogle Scholar
  11. 11.
    Feng IC, Koay LB, Sheu MJ, Kuo HT, Sun CS, Lee C, et al. HBcAg-specific CD4 + CD25 + regulatory T cells modulate immune tolerance and acute exacerbation on the natural history of chronic hepatitis B virus infection. J Biomed Sci. 2007;14:43–57.CrossRefPubMedGoogle Scholar
  12. 12.
    Koay LB, Feng IC, Sheu MJ, Kuo HT, Lin CY, Chen JJ, et al. Hepatitis B virus (HBV) core antigen-specific regulatory T cells confer sustained remission to anti-HBV therapy in chronic hepatitis B with acute exacerbation. Hum Immunol. 2011;72:687–98.CrossRefPubMedGoogle Scholar
  13. 13.
    Liaw YF, Tsai SL, Chien RN, Yeh CT, Chu CM. Prednisolone priming enhances Th1 response and efficacy of subsequent lamivudine therapy in patients with chronic hepatitis B. Hepatology. 2000;32:604–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Hanson RG, Peters MG, Hoofnagle JH. Effects of immunosuppressive therapy with prednisolone on B and T lymphocyte function in patients with chronic type B hepatitis. Hepatology. 1986;6:173–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Tseng TC, Liu CJ, Hsieh SC, Chen PJ, Lai MY, Chen DS, et al. Reactivation of hepatitis B virus in an inactive hepatitis B carrier with glucocorticoid pulse therapy. Dig Liver Dis. 2009;41:322–3.CrossRefPubMedGoogle Scholar
  16. 16.
    Yeo W, Chan PK, Zhong S, Ho WM, Steinberg JL, Tam JS, et al. Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy: a prospective study of 626 patients with identification of risk factors. J Med Virol. 2000;62:299–307.CrossRefPubMedGoogle Scholar
  17. 17.
    Lau GK, Leung YH, Fong DY, Au WY, Kwong YL, Lie A, et al. High hepatitis B virus (HBV) DNA viral load as the most important risk factor for HBV reactivation in patients positive for HBV surface antigen undergoing autologous hematopoietic cell transplantation. Blood. 2002;99:2324–30.CrossRefPubMedGoogle Scholar
  18. 18.
    Sheen IS, Liaw YF, Lin SM, Chu CM. Severe clinical rebound upon withdrawal of corticosteroid before interferon therapy: incidence and risk factors. J Gastroenterol Hepatol. 1996;11:143–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Buttgereit F, Straub RH, Wehling M, Burmester GR. Glucocorticoids in the treatment of rheumatic diseases: an update on the mechanisms of action. Arthritis Rheum. 2004;50:3408–17.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Ying-Cheng Lin
    • 1
  • Shou-Wu Lee
    • 1
    • 2
  • Hong-Zen Yeh
    • 1
    • 3
  • Chi-Sen Chang
    • 1
    • 2
  • Sheng-Shun Yang
    • 1
    • 3
    Email author
  1. 1.Division of Gastroenterology and Hepatology, Department of Internal MedicineTaichung Veterans General HospitalTaichungTaiwan
  2. 2.School of MedicineChung Shan Medical UniversityTaichungTaiwan
  3. 3.Faculty of Medicine, College of MedicineNational Yang- Ming UniversityTaipeiTaiwan

Personalised recommendations