Journal of Gastroenterology

, Volume 43, Issue 9, pp 711–719 | Cite as

Efficacy of combination therapy of antiviral and immunosuppressive drugs for the treatment of severe acute exacerbation of chronic hepatitis B

  • Keiichi Fujiwara
  • Shin Yasui
  • Yutaka Yonemitsu
  • Kenichi Fukai
  • Makoto Arai
  • Fumio Imazeki
  • Akihiro Suzuki
  • Hiroshi Suzuki
  • Tomohito Sadahiro
  • Shigeto Oda
  • Osamu Yokosuka
Liver, Pancreas, and Biliary Tract

Abstract

Background

Patients with severe exacerbation of chronic hepatitis B, sometimes developing into fulminant liver failure, are at high risk for mortality even with antiviral therapy. The efficacy of immunosuppressive therapy in clinically severe exacerbation of chronic hepatitis B has not been well demonstrated. In this study, we evaluated the efficacy of the early introduction of immunosuppressive therapy in combination with antiviral therapy in such patients.

Methods

Forty-two patients, 29 men and 13 women, were defined as having severe exacerbation of chronic hepatitis B based on our uniform criteria, and were enrolled in this study. Sixteen patients between 1982 and 1996 were analyzed retrospectively. We defined the criteria of severe disease in 1997, and then began to introduce sufficient doses of corticosteroids prospectively. Nucleoside analogs were administered in combination with corticosteroids after 1999. Twenty-six patients between 1997 and 2007 were analyzed prospectively.

Results

In the retrospective study between 1982 and 1996, four of 16 (25%) patients recovered. In the prospective study between 1997 and 2007, 17 of 26 (65%) patients recovered; 15 of 17 patients treated with corticosteroids with or without antiviral drugs within 10 days after the diagnosis of severe disease recovered, none of five treated similarly but later than 10 days after the diagnosis recovered, and two of three treated with antiviral drugs recovered.

Conclusions

The early introduction of sufficient doses of corticosteroids and nucleoside analogs could be one option for reversing the potential deterioration of patients with clinically severe, life-threatening exacerbation of chronic hepatitis B.

Key words

chronic hepatitis B severe exacerbation immunosuppressive therapy antiviral therapy 

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References

  1. 1.
    Editorial. Chemotherapy and hepatitis B. Lancet 1989;ii:1136–1137.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;78:2210–2215.PubMedCrossRefGoogle Scholar
  3. 3.
    Chisari FV, Ferrari C. Hepatitis B virus immunopathogenesis. Annu Rev Immunol 1995;13:29–60.PubMedCrossRefGoogle 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;7:582–585.PubMedCrossRefGoogle 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;304:380–386.PubMedGoogle 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;104:12–17.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;81:987–991.PubMedGoogle Scholar
  8. 8.
    Lau JY, Bird GL, Gimson AE, Alexander GJ, Williams R. Treatment of HBV reactivation after withdrawal of immunosuppression. Lancet 1991;337:802.PubMedCrossRefGoogle Scholar
  9. 9.
    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;11:1109–1114PubMedGoogle Scholar
  10. 10.
    Santantonio T, Mazzola M, Pastore G. Lamivudine is safe and effective in fulminant hepatitis B. J Hepatol 1999;30:551–553.PubMedCrossRefGoogle Scholar
  11. 11.
    Van Thiel DH, Friedlander L, Kania RJ, Molloy PJ, Hassanein T, Wahlstrom E, et al. Lamivudine treatment of advanced and decompensated liver disease due to hepatitis B. Hepatogastroenterology 1997;44:808–812.PubMedGoogle Scholar
  12. 12.
    Chan TM, Wu PC, Li FK, Lai CL, Cheng IK, Lai KN. Treatment of fibrosing cholestatic hepatitis with lamivudine. Gastroenterology 1998;115:177–181.PubMedCrossRefGoogle Scholar
  13. 13.
    ter Borg F, Smorenburg S, de Man RA, Rietbroek RC, Chamuleau RA, Jones EA. Recovery from life-threatening corticosteroid-unresponsive chemotherapy-related reactivation of hepatitis B associated with lamivudine therapy. Dig Dis Sci 1998;43:2267–2270.PubMedCrossRefGoogle Scholar
  14. 14.
    Ahmed A, Keeffe EB. Lamivudine therapy for chemotherapyinduced reactivation of hepatitis B virus infection. Am J Gastroenterol 1999;94:249–251.PubMedCrossRefGoogle Scholar
  15. 15.
    Villeneuve JP, 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;31:207–210.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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;60:215–222.PubMedGoogle Scholar
  18. 18.
    Kaplan PM, Greenman RL, Gerin TL, Purcell RH, Robinson WS. DNA polymerase associated with human hepatitis B antigen. J Virol 1973;12:995–1005.PubMedGoogle Scholar
  19. 19.
    Markovic S, Drozina G, Vovk M, Fidler-Jenko M. Reactivation of hepatitis B but not hepatitis C in patients with malignant lymphoma and immunosuppressive therapy. A prospective study in 305 patients. Hepatogastroenterology 1999;46:2925–2930.PubMedGoogle Scholar
  20. 20.
    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;38:646–657.PubMedCrossRefGoogle Scholar
  21. 21.
    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;20:426–432.PubMedCrossRefGoogle Scholar
  22. 22.
    Chan HL, Tsang SW, Hui Y, Leung NW, Chan FK, Sung JJ. The role of lamivudine and predictors of mortality in severe flare-up of chronic hepatitis B with jaundice. J Viral Hepat 2002;9:424–428.PubMedCrossRefGoogle Scholar
  23. 23.
    Chien RN, Lin CH, Liaw YF. The effect of lamivudine therapy in hepatic decompensation during acute exacerbation of chronic hepatitis B. J Hepatol 2003;38:322–327.PubMedCrossRefGoogle Scholar
  24. 24.
    Tur-Kaspa R, Burk RD, Shaul Y, Shafritz DA. Hepatitis B virus DNA contains a glucocorticoid-responsive element. Proc Natl Acad Sci USA 1986;83:1627–1631.PubMedCrossRefGoogle Scholar
  25. 25.
    Gregory PB, Knauer M, Kempson RL, Miller R. Steroid therapy in severe viral hepatitis. N Engl J Med 1976;294:681–687.PubMedGoogle Scholar

Copyright information

© Springer Japan 2008

Authors and Affiliations

  • Keiichi Fujiwara
    • 1
  • Shin Yasui
    • 1
  • Yutaka Yonemitsu
    • 1
  • Kenichi Fukai
    • 1
  • Makoto Arai
    • 1
  • Fumio Imazeki
    • 1
  • Akihiro Suzuki
    • 2
  • Hiroshi Suzuki
    • 2
  • Tomohito Sadahiro
    • 3
  • Shigeto Oda
    • 3
  • Osamu Yokosuka
    • 1
  1. 1.Department of Medicine and Clinical Oncology, Graduate School of MedicineChiba UniversityChibaJapan
  2. 2.Takushinkai Tatsumi HospitalIchiharaJapan
  3. 3.Department of Emergency and Critical Care Medicine, Graduate School of MedicineChiba UniversityChibaJapan

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