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Journal of Gastroenterology

, Volume 45, Issue 12, pp 1255–1262 | Cite as

The requirement for a sufficient period of corticosteroid treatment in combination with nucleoside analogue for severe acute exacerbation of chronic hepatitis B

  • Keiichi FujiwaraEmail author
  • Shin Yasui
  • Koichiro Okitsu
  • Yutaka Yonemitsu
  • Shigeto Oda
  • Osamu Yokosuka
Original Article—Liver, Pancreas, and Biliary Tract

Abstract

Background

The prognosis of severe acute exacerbation of chronic hepatitis B is very poor if signs of liver failure appear. We have reported the efficacy of the early introduction of sufficient doses of corticosteroids (CSs) and nucleoside analogues (NAs), but the optimal period of immunosuppressive therapy has not been well demonstrated. In this study, we analyzed patients with severe acute exacerbation of chronic hepatitis B treated with CSs and NAs, prospectively, in order to clarify the factors affecting their outcome.

Methods

Ten patients, admitted to our liver unit between 2000 and 2009, were defined as having severe exacerbation of chronic hepatitis B based on our uniform criteria, and were enrolled in this study. NAs and sufficient doses of CS were introduced as soon as possible after making the diagnosis of severe disease prospectively.

Results

Seven of the 10 patients recovered. The absence of fulminant hepatitis on admission, the improvement of prothrombin time (PT) activity and the decline of hepatitis B virus (HBV) DNA during the first 2 and 4 weeks, respectively, were significant in the recovered patients, while the worsening of total bilirubin level during 4 weeks, especially between week 2 and week 4, was significant in those who died.

Conclusions

In severe acute exacerbation of chronic hepatitis B, more than a few weeks of CS treatment in combination with an NA is required in the early stage, whereas a short period of conventional pulse therapy would be insufficient for treating this condition.

Keywords

Chronic hepatitis B Severe exacerbation Corticosteroid Nucleoside analogue 

Abbreviations

HBV

Hepatitis B virus

CS

Corticosteroid

NA

Nucleoside analogue

Notes

Acknowledgments

We are indebted to all our colleagues at the liver units of our hospitals who cared for the patients described herein.

Conflict of interest statement

No conflicts of interest exist.

References

  1. 1.
    Editorial. Chemotherapy and hepatitis B. Lancet 1989; ii:1136–7.Google Scholar
  2. 2.
    Nakamura Y, Motokura T, Fujita R, Yamashita T, Ogata E. Severe hepatitis related to chemotherapy in hepatitis B virus carriers with hematologic malignancies. Cancer. 1996;78:2210–5.CrossRefPubMedGoogle Scholar
  3. 3.
    Chisari FV, Ferrari C. Hepatitis B virus immunopathogenesis. Annu Rev Immunol. 1995;13:29–60.CrossRefPubMedGoogle Scholar
  4. 4.
    Sjogren MH, Hoofnagle JH, Waggoner JG. Effect of corticosteroid therapy on levels of antibody to hepatitis B core antigen in patients with chronic type B hepatitis. Hepatology. 1987;7:582–5.CrossRefPubMedGoogle Scholar
  5. 5.
    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
  6. 6.
    Hoofnagle JH, Davis GL, Pappas SC, Hanson RG, Peters M, Avigan MI, et al. A short course of prednisolone in chronic type B hepatitis. Ann Intern Med. 1986;104:12–7.PubMedGoogle Scholar
  7. 7.
    Scullard GH, Smith CI, Merigan TC, Robinson WS, Gregory PB. Effects of immunosuppressive therapy on viral markers in chronic active hepatitis B. Gastroenterology. 1981;81:987–91.PubMedGoogle Scholar
  8. 8.
    Lau JYN, Bird GLA, Gimson AES, Alexander GJM, Williams R. Treatment of HBV reactivation after withdrawal of immunosuppression. Lancet. 1991;337:802.CrossRefPubMedGoogle Scholar
  9. 9.
    Santantonio T, Mazzola M, Pastore G. Lamivudine is safe and effective in fulminant hepatitis B. J Hepatol. 1999;30:551–3.CrossRefPubMedGoogle Scholar
  10. 10.
    Chan T-M, Wu P-C, Li F-K, Lai C-L, Cheng IKP, Lai K-N. Treatment of fibrosing cholestatic hepatitis with lamivudine. Gastroenterology. 1998;115:177–81.CrossRefPubMedGoogle Scholar
  11. 11.
    Borg FT, Smorenburg S, de Man RA, Rietbroek RC, Chamuleau RAFM. Recovery from life-threatening corticosteroid-unresponsive chemotherapy-related reactivation of hepatitis B associated with lamivudine therapy. Dig Dis Sci. 1998;43:2267–70.CrossRefPubMedGoogle Scholar
  12. 12.
    Ahmed A, Keeffe EB. Lamivudine therapy for chemotherapy-induced reactivation of hepatitis B virus infection. Am J Gastroenterol. 1999;94:249–51.CrossRefPubMedGoogle Scholar
  13. 13.
    Villeneuve J-P, Condreay LD, Willems B, Pomier-Layrargues G, Fenyves D, Bilodeau M, et al. Lamivudine treatment for decompensated cirrhosis resulting from chronic hepatitis B. Hepatology. 2000;31:207–10.CrossRefPubMedGoogle Scholar
  14. 14.
    Fujiwara K, Yokosuka O, Kojima H, Kanda T, Saisho H, Hirasawa H, et al. Importance of adequate immunosuppressive therapy for the recovery of patients with “life-threatening” severe exacerbation of chronic hepatitis B. World J Gastroenterol. 2005;11:1109–14.PubMedGoogle Scholar
  15. 15.
    Fujiwara K, Yasui S, Yonemitsu Y, Fukai K, Arai M, Imazeki F, et al. Efficacy of combination therapy of antiviral and immunosuppressive drugs for the treatment of severe acute exacerbation of chronic hepatitis B. J Gastroenterol. 2008;43:711–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Iino S, Tango T, Matsushima T, Toda G, Miyake K, Hino K, et al. Therapeutic effects of stronger neo-minophagen C at different doses on chronic hepatitis and liver cirrhosis. Hepatol Res. 2001;19:31–40.CrossRefPubMedGoogle Scholar
  17. 17.
    Okamoto H, Okada S, Sugiyama Y, Tanaka T, Sugai Y, Akahane Y, et al. Detection of hepatitis C virus RNA by a two-step polymerase chain reaction with two pairs of primers deduced from the 5′-noncoding region. Jpn J Exp Med. 1990;60:215–22.PubMedGoogle Scholar
  18. 18.
    Fujiwara K, Mochida S, Matsui A, Nakayama N, Nagoshi S, Toda G. Intractable Liver Diseases Study Group of Japan. Fulminant hepatitis and late onset hepatic failure in Japan. Hepatol Res. 2008;38:646–57.CrossRefPubMedGoogle Scholar
  19. 19.
    Hoofnagle JH. Reactivation of hepatitis B. Hepatology. 2009;49:S156–65.CrossRefPubMedGoogle Scholar
  20. 20.
    Tsubota A, Arase Y, Suzuki Y, Suzuki F, Sezaki H, Hosaka T, et al. Lamivudine monotherapy for spontaneous severe acute exacerbation of chronic hepatitis B. J Gastroenterol Hepatol. 2005;20:426–32.CrossRefPubMedGoogle Scholar
  21. 21.
    Chien RN, Lin CH, Liaw YF. The effect of lamivudine therapy in hepatic decompensation during acute exacerbation of chronic hepatitis B. J Hepatol. 2003;38:322–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Tur-Kaspa R, Burk RD, Shaul Y, Shafritz DA. Hepatitis B virus DNA contains a glucocorticoid-responsive element. Proc Natl Acad Sci USA. 1986;83:1627–31.CrossRefPubMedGoogle Scholar
  23. 23.
    Gregory PB, Knauer M, Kempson RL, Miller R. Steroid therapy in severe viral hepatitis. N Engl J Med. 1976;294:681–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Hansson BG, Riesbeck K, Nordenfelt E, Weiland O. Successful treatment of fulminant hepatitis B and fulminant hepatitis B and D coinfection explained by inhibitory effect on the immune response? Prog Clin Biol Res. 1991;364:421–7.PubMedGoogle Scholar
  25. 25.
    Matsumoto K, Miyake Y, Miyatake H, Takahara M, Imada T, Yagi S, et al. A combination treatment of entecavir and early-phase corticosteroid in severe exacerbation of chronic hepatitis B. World J Gastroenterol. 2009;15:1650–2.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2010

Authors and Affiliations

  • Keiichi Fujiwara
    • 1
    Email author
  • Shin Yasui
    • 1
  • Koichiro Okitsu
    • 1
  • Yutaka Yonemitsu
    • 1
  • Shigeto Oda
    • 2
  • Osamu Yokosuka
    • 1
  1. 1.Department of Medicine and Clinical Oncology, Graduate School of MedicineChiba UniversityChibaJapan
  2. 2.Department of Emergency and Critical Care Medicine, Graduate School of MedicineChiba UniversityChibaJapan

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