Skip to main content
  • 472 Accesses

Abstract

Hepatitis B virus (HBV) reactivation is defined as HBV reproliferation under specific conditions, such as immunosuppression. A state of reactivation counteracts a state of immunosuppression. Thus, hepatitis that occurs due to an attack on HBV-infected hepatocytes by a recovered immune system is known as de novo hepatitis B infection. HBV reactivation is induced by various agents that are used for chemotherapy and immunosuppressive therapy, and the risk of reactivation determines the severity of both HBV infection and immunosuppression. Several reports have described HBV reactivation due to antirheumatic agents used to treat rheumatic and connective tissue disorders. However, HBV reactivation does not occur frequently, and immunosuppressive treatment is usually long term; thus, the risk of hepatitis onset due to an immune response is low. However, de novo hepatitis B infection tends to be severe, and if the patient becomes ill, the mortality risk is not only high, but treatment of the underlying disease is also complicated by hepatitis onset. Therefore, preventing onset itself is of primary importance. Currently, according to the “Guidelines for the Management of Hepatitis B Virus Reactivation Caused by Immunosuppression/Chemotherapy”, it is imperative to perform monitoring and administer preventive treatment with nucleic acid analogues to all patients with rheumatic and connective tissue disorders who are likely to develop hepatitis B reactivation. In addition, future research should consider clarifying viral and host factors related to HBV reactivation and severity to define high-risk patients.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11(2):97–107.

    Article  CAS  Google Scholar 

  2. McMahon BJ. Natural history of chronic hepatitis B. Clin Liver Dis. 2010;14(3):381–96.

    Article  Google Scholar 

  3. Ganem D, Prince AM. Hepatitis B virus infection—natural history and clinical consequences. N Engl J Med. 2004;350(11):1118–29.

    Article  CAS  Google Scholar 

  4. Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol. 2008;48(2):335–52.

    Article  Google Scholar 

  5. Hoofnagle JH. Reactivation of hepatitis B. Hepatology. 2009;49(5 Suppl):S156–65.

    Article  CAS  Google Scholar 

  6. Dervite I, Hober D, Morel P. Acute hepatitis B in a patient with antibodies to hepatitis B surface antigen who was receiving rituximab. N Engl J Med. 2001;344(1):68–9.

    Article  CAS  Google Scholar 

  7. Westhoff TH, Jochimsen F, Schmittel A, Stoffler-Meilicke M, Schafer JH, Zidek W, et al. Fatal hepatitis B virus reactivation by an escape mutant following rituximab therapy. Blood. 2003;102(5):1930.

    Article  CAS  Google Scholar 

  8. Hui CK, Cheung WW, Zhang HY, Au WY, Yueng YH, Leung AY, et al. Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy. Gastroenterology. 2006;131(1):59–68.

    Article  CAS  Google Scholar 

  9. Berger A, Preiser W, Kachel HG, Sturmer M, Doerr HW. HBV reactivation after kidney transplantation. J Clin Virol. 2005;32(2):162–5.

    Article  CAS  Google Scholar 

  10. Tanaka E, Umemura T. History and prevention of de novo hepatitis B virus-related hepatitis in Japan and the world. Clin J Gastroenterol. 2008;1(3):83–6.

    Article  Google Scholar 

  11. Kusumoto S, Tanaka Y, Suzuki R, Watanabe T, Nakata M, Takasaki H, et al. Monitoring of hepatitis B virus (HBV) DNA and risk of HBV reactivation in B-cell lymphoma: a prospective observational study. Clin Infect Dis. 2015;61(5):719–29.

    Article  CAS  Google Scholar 

  12. Yeo W, Chan PK, Ho WM, Zee B, Lam KC, Lei KI, et al. Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis B s-antigen seropositive cancer patients undergoing cytotoxic chemotherapy. J Clin Oncol. 2004;22(5):927–34.

    Article  CAS  Google Scholar 

  13. Lok AS, Liang RH, Chiu EK, Wong KL, Chan TK, Todd D. Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Report of a prospective study. Gastroenterology. 1991;100(1):182–8.

    Article  CAS  Google Scholar 

  14. Lau GK, Yiu HH, Fong DY, Cheng HC, Au WY, Lai LS, et al. Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy. Gastroenterology. 2003;125(6):1742–9.

    Article  CAS  Google Scholar 

  15. Yeo W, Lam KC, Zee B, Chan PS, Mo FK, Ho WM, et al. Hepatitis B reactivation in patients with hepatocellular carcinoma undergoing systemic chemotherapy. Ann Oncol. 2004;15(11):1661–6.

    Article  CAS  Google Scholar 

  16. Sohn BS, Ahn JH, Jung KH, Ahn SH, Son BH, Gong G, et al. Updated longitudinal data on acute exacerbation of chronic hepatitis B in patients with breast cancer receiving anthracycline-based adjuvant chemotherapy: therapeutic vs. pre-emptive use of lamivudine. Jpn J Clin Oncol. 2011;41(9):1059–66.

    Article  Google Scholar 

  17. Kim MK, Ahn JH, Kim SB, Im YS, Lee SI, Ahn SH, et al. Hepatitis B reactivation during adjuvant anthracycline-based chemotherapy in patients with breast cancer: a single institution’s experience. Korean J Intern Med. 2007;22(4):237–43.

    Article  CAS  Google Scholar 

  18. Jang JW, Choi JY, Bae SH, Kim CW, Yoon SK, Cho SH, et al. Transarterial chemo-lipiodolization can reactivate hepatitis B virus replication in patients with hepatocellular carcinoma. J Hepatol. 2004;41(3):427–35.

    Article  CAS  Google Scholar 

  19. Dai CY, Yeh ML, Huang CF, Huang JF, Yu ML, Chuang WL. Outcome of patients suffering from a spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure and treated with antivirals. Hepatology. 2011;54(3):1108–9.

    Article  Google Scholar 

  20. 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(6):1320–8.

    Article  CAS  Google Scholar 

  21. Nakamura Y, Motokura T, Fujita A, Yamashita T, Ogata E. Severe hepatitis related to chemotherapy in hepatitis B virus carriers with hematologic malignancies. Survey in Japan, 1987–1991. Cancer. 1996;78(10):2210–5.

    Article  CAS  Google Scholar 

  22. Yeo W, Zee B, Zhong S, Chan PK, Wong WL, Ho WM, et al. Comprehensive analysis of risk factors associating with hepatitis B virus (HBV) reactivation in cancer patients undergoing cytotoxic chemotherapy. Br J Cancer. 2004;90(7):1306–11.

    Article  CAS  Google Scholar 

  23. Zhu AX, Kudo M, Assenat E, Cattan S, Kang YK, Lim HY, et al. Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial. JAMA. 2014;312(1):57–67.

    Article  Google Scholar 

  24. Yeo W, Chan TC, Leung NW, Lam WY, Mo FK, Chu MT, et al. Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab. J Clin Oncol. 2009;27(4):605–11.

    Article  CAS  Google Scholar 

  25. Targhetta C, Cabras MG, Mamusa AM, Mascia G, Angelucci E. Hepatitis B virus-related liver disease in isolated anti-hepatitis B-core positive lymphoma patients receiving chemo- or chemo-immune therapy. Haematologica. 2008;93(6):951–2.

    Article  Google Scholar 

  26. Peng JW, Lin GN, Xiao JJ, Jiang XM. Hepatitis B virus reactivation in hepatocellular carcinoma patients undergoing transcatheter arterial chemoembolization therapy. Asia Pac J Clin Oncol. 2012;8(4):356–61.

    Article  Google Scholar 

  27. Pei SN, Chen CH, Lee CM, Wang MC, Ma MC, Hu TH, et al. Reactivation of hepatitis B virus following rituximab-based regimens: a serious complication in both HBsAg-positive and HBsAg-negative patients. Ann Hematol. 2010;89(3):255–62.

    Article  CAS  Google Scholar 

  28. 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(29):2925–30.

    CAS  PubMed  Google Scholar 

  29. Koo YX, Tay M, Teh YE, Teng D, Tan DS, Tan IB, et al. Risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen negative/hepatitis B core antibody positive patients receiving rituximab-containing combination chemotherapy without routine antiviral prophylaxis. Ann Hematol. 2011;90(10):1219–23.

    Article  CAS  Google Scholar 

  30. Kim E, Yune S, Ha JM, Lee WJ, Hwang JW, Paik YH, et al. Hepatitis B virus reactivation during anti-cancer chemotherapy in patients with past hepatitis B virus infection. Hepatogastroenterology. 2014;61(134):1704–11.

    PubMed  Google Scholar 

  31. Watanabe R, Ishii T, Kobayashi H, Asahina I, Takemori H, Izumiyama T, et al. Prevalence of hepatitis B virus infection in patients with rheumatic diseases in Tohoku area: a retrospective multicenter survey. Tohoku J Exp Med. 2014;233(2):129–33.

    Article  Google Scholar 

  32. Urata Y, Uesato R, Tanaka D, Kowatari K, Nitobe T, Nakamura Y, et al. Prevalence of reactivation of hepatitis B virus replication in rheumatoid arthritis patients. Mod Rheumatol. 2011;21(1):16–23.

    Article  CAS  Google Scholar 

  33. Caporali R, Bobbio-Pallavicini F, Atzeni F, Sakellariou G, Caprioli M, Montecucco C, et al. Safety of tumor necrosis factor alpha blockers in hepatitis B virus occult carriers (hepatitis B surface antigen negative/anti-hepatitis B core antigen positive) with rheumatic diseases. Arthritis Care Res (Hoboken). 2010;62(6):749–54.

    Article  CAS  Google Scholar 

  34. Charpin C, Guis S, Colson P, Borentain P, Mattei JP, Alcaraz P, et al. Safety of TNF-blocking agents in rheumatic patients with serology suggesting past hepatitis B state: results from a cohort of 21 patients. Arthritis Res Ther. 2009;11(6):R179.

    Article  Google Scholar 

  35. 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(10):1719–25.

    Article  CAS  Google Scholar 

  36. Nakamura J, Nagashima T, Nagatani K, Yoshio T, Iwamoto M, Minota S. Reactivation of hepatitis B virus in rheumatoid arthritis patients treated with biological disease-modifying antirheumatic drugs. Int J Rheum Dis. 2016;19(5):470–5.

    Article  CAS  Google Scholar 

  37. Tamori A, Koike T, Goto H, Wakitani S, Tada M, Morikawa H, et al. Prospective study of reactivation of hepatitis B virus in patients with rheumatoid arthritis who received immunosuppressive therapy: evaluation of both HBsAg-positive and HBsAg-negative cohorts. J Gastroenterol. 2011;46(4):556–64.

    Article  CAS  Google Scholar 

  38. Tan J, Zhou J, Zhao P, Wei J. Prospective study of HBV reactivation risk in rheumatoid arthritis patients who received conventional disease-modifying antirheumatic drugs. Clin Rheumatol. 2012;31(8):1169–75.

    Article  Google Scholar 

  39. Fukuda W, Hanyu T, Katayama M, Mizuki S, Okada A, Miyata M, et al. Incidence of hepatitis B virus reactivation in patients with resolved infection on immunosuppressive therapy for rheumatic disease: a multicentre, prospective, observational study in Japan. Ann Rheum Dis. 2017;76(6):1051–6.

    Article  CAS  Google Scholar 

  40. Mochida S, Nakao M, Nakayama N, Uchida Y, Nagoshi S, Ido A, et al. Nationwide prospective and retrospective surveys for hepatitis B virus reactivation during immunosuppressive therapies. J Gastroenterol. 2016;51(10):999–1010.

    Article  CAS  Google Scholar 

  41. Ohira H, Abe K, Takahashi A. Involvement of the liver in rheumatic diseases. Clin J Gastroenterol. 2012;5(1):9–14.

    Article  Google Scholar 

  42. Umemura T, Tanaka E, Kiyosawa K, Kumada H. Japan de novo Hepatitis BRG. Mortality secondary to fulminant hepatic failure in patients with prior resolution of hepatitis B virus infection in Japan. Clin Infect Dis. 2008;47(5):e52–6.

    Article  Google Scholar 

  43. Hsu C, Hsiung CA, Su IJ, Hwang WS, Wang MC, Lin SF, et al. A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin’s lymphoma: a randomized trial. Hepatology. 2008;47(3):844–53.

    Article  CAS  Google Scholar 

  44. Lau GK, He ML, Fong DY, Bartholomeusz A, Au WY, Lie AK, et al. Preemptive use of lamivudine reduces hepatitis B exacerbation after allogeneic hematopoietic cell transplantation. Hepatology. 2002;36(3):702–9.

    Article  CAS  Google Scholar 

  45. Loomba R, Rowley A, Wesley R, Liang TJ, Hoofnagle JH, Pucino F, et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med. 2008;148(7):519–28.

    Article  Google Scholar 

  46. Shinkai N, Tanaka Y, Orito E, Ito K, Ohno T, Hirashima N, et al. Measurement of hepatitis B virus core-related antigen as predicting factor for relapse after cessation of lamivudine therapy for chronic hepatitis B virus infection. Hepatol Res. 2006;36(4):272–6.

    Article  CAS  Google Scholar 

  47. Matsumoto A, Tanaka E, Minami M, Okanoue T, Yatsuhashi H, Nagaoka S, et al. Low serum level of hepatitis B core-related antigen indicates unlikely reactivation of hepatitis after cessation of lamivudine therapy. Hepatol Res. 2007;37(8):661–6.

    Article  CAS  Google Scholar 

  48. Matsumoto A, Tanaka E, Suzuki Y, Kobayashi M, Tanaka Y, Shinkai N, et al. Combination of hepatitis B viral antigens and DNA for prediction of relapse after discontinuation of nucleos(t)ide analogs in patients with chronic hepatitis B. Hepatol Res. 2012;42(2):139–49.

    Article  CAS  Google Scholar 

  49. Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130(3):678–86.

    Article  Google Scholar 

  50. Tanaka E, Matsumoto A. Guidelines for avoiding risks resulting from discontinuation of nucleoside/nucleotide analogs in patients with chronic hepatitis B. Hepatol Res. 2014;44(1):1–8.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ken Okai .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Okai, K., Abe, K., Takahashi, A., Ohira, H. (2019). De Novo Hepatitis B Virus Infection. In: Ohira, H., Migita, K. (eds) Gastrointestinal and Hepatic Manifestations of Rheumatic Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-13-6524-9_3

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-6524-9_3

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-6523-2

  • Online ISBN: 978-981-13-6524-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics