Skip to main content

Advertisement

SpringerLink
Log in

Hepatitis B virus reactivation in rheumatoid arthritis and ankylosing spondylitis patients treated with anti-TNFα agents: A retrospective analysis of 49 cases

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Clinical guidelines regarding anti-viral prophylaxis for HBV surface antigen (HBsAg) carriers starting anti-TNFα agents are not yet fully established, even in endemic regions of HBV infection. We retrospectively collected the clinical data of 52 HBsAg carriers with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) that had been administered anti-TNFα treatment at seven medical centers in South Korea. Periodic data of liver function tests and serum HBV DNA were both utilized to assess HBV reactivation. The YMDD motif mutation of HBV DNA polymerase was tested in lamivudine-treated patients with elevated HBV DNA. Three of the 52 patients were excluded from the analysis. Of the 49 analyzed patients, 20 patients received anti-viral prophylaxis (15 lamivudine, five entecavir) with anti-TNFα treatment. The remaining 29 patients were treated with anti-viral agents if needed at the discretion of the clinician and did not receive prophylaxis. Of the 29 patients who did not receive primary prophylaxis, two (6.9%) developed viral reactivation within a year of anti-TNFα treatment. In the prophylaxis group, one patient developed viral reactivation at week 64 of anti-TNFα therapy attributed to YMDD mutation caused by lamivudine. Patients with HBV reactivation all responded well to anti-viral therapy. In summary, anti-viral prophylaxis helped preventing HBV reactivation in HBsAg carriers with RA or AS starting anti-TNFα, yet mutation in the YMDD motif of HBV DNA polymerase could be detrimental to some patients under long-term lamivudine prophylaxis.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Raychaudhuri SP, Nguyen CT, Raychaudhuri SK et al (2009) Incidence and nature of infectious disease in patients treated with anti-TNF agents. Autoimmun Rev 9:67–81

    Article  PubMed  CAS  Google Scholar 

  2. Keane J, Gershon S, Wise RP et al (2001) Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 345:1098–1104

    Article  PubMed  CAS  Google Scholar 

  3. Gupta S, Govindarajan S, Fong TL et al (1990) Spontaneous reactivation in chronic hepatitis B: patterns and natural history. J Clin Gastroenterol 12:562–568

    Article  PubMed  CAS  Google Scholar 

  4. Perrillo RP (2001) Acute flares in chronic hepatitis B: the natural and unnatural history of an immunologically mediated liver disease. Gastroenterology 120:1009–1022

    Article  PubMed  CAS  Google Scholar 

  5. Esteve M, Saro C, Gonzalez-Huix F et al (2004) Chronic hepatitis B reactivation following infliximab therapy in Crohn’s disease patients: need for primary prophylaxis. Gut 53:1363–1365

    Article  PubMed  CAS  Google Scholar 

  6. Sakellariou GT, Chatzigiannis I (2007) Long-term anti-TNFalpha therapy for ankylosing spondylitis in two patients with chronic HBV infection. Clin Rheumatol 26:950–952

    Article  PubMed  Google Scholar 

  7. Carroll MB, Bond MI (2008) Use of tumor necrosis factor-alpha inhibitors in patients with chronic hepatitis B infection. Semin Arthritis Rheum 38:208–217

    Article  PubMed  CAS  Google Scholar 

  8. Ojiro K, Naganuma M, Ebinuma H et al (2008) Reactivation of hepatitis B in a patient with Crohn’s disease treated using infliximab. J Gastroenterol 43:397–401

    Article  PubMed  Google Scholar 

  9. Chung SJ, Kim JK, Park MC et al (2009) Reactivation of hepatitis B viral infection in inactive HBsAg carriers following anti-tumor necrosis factor-alpha therapy. J Rheumatol 36:2416–2420

    Article  PubMed  CAS  Google Scholar 

  10. Kim YJ, Bae SC, Sung YK et al (2010) Possible reactivation of potential hepatitis B virus occult infection by tumor necrosis factor-alpha blocker in the treatment of rheumatic diseases. J Rheumatol 37:346–350

    Article  PubMed  Google Scholar 

  11. Lan JL, Chen YM, Hsieh TY et al (2011) 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 70:1719–1725

    Article  PubMed  CAS  Google Scholar 

  12. Tamori A, Koike T, Goto H et al (2011) 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 46:556–564

    Article  PubMed  CAS  Google Scholar 

  13. Ganem D, Prince AM (2004) Hepatitis B virus infection—natural history and clinical consequences. N Engl J Med 350:1118–1129

    Article  PubMed  CAS  Google Scholar 

  14. Guidotti LG, Ishikawa T, Hobbs MV et al (1996) Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity 4:25–36

    Article  PubMed  CAS  Google Scholar 

  15. Guidotti LG, Ando K, Hobbs MV et al (1994) Cytotoxic T lymphocytes inhibit hepatitis B virus gene expression by a noncytolytic mechanism in transgenic mice. Proc Natl Acad Sci U S A 91:3764–3768

    Article  PubMed  CAS  Google Scholar 

  16. Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    Article  PubMed  CAS  Google Scholar 

  17. van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27:361–368

    Article  PubMed  Google Scholar 

  18. Hoofnagle JH (2009) Reactivation of hepatitis B. Hepatology 49:S156–S165

    Article  PubMed  CAS  Google Scholar 

  19. Korea Centers for Disease Control and Prevention (2007) The Fourth Korea National Health and Nutrition Examination Survey (KNHANES III), pp 70–71

  20. Kuwabara H, Fukuda A, Tsuda Yet al (2010) Precore mutant hepatitis B virus-associated fulminant hepatitis during infliximab therapy for rheumatoid arthritis. Clin Rheumatol

  21. Michel M, Duvoux C, Hezode C et al (2003) Fulminant hepatitis after infliximab in a patient with hepatitis B virus treated for an adult onset Still’s disease. J Rheumatol 30:1624–1625

    PubMed  Google Scholar 

  22. Dienstag JL (2008) Hepatitis B virus infection. N Engl J Med 359:1486–1500

    Article  PubMed  CAS  Google Scholar 

  23. Vassilopoulos D, Apostolopoulou A, Hadziyannis E et al (2010) Long-term safety of anti-TNF treatment in patients with rheumatic diseases and chronic or resolved hepatitis B virus infection. Annals Rheum Dis 69:1352–1355

    Article  CAS  Google Scholar 

  24. Colonno RJ, Rose R, Baldick CJ et al (2006) Entecavir resistance is rare in nucleoside naive patients with hepatitis B. Hepatology 44:1656–1665

    Article  PubMed  CAS  Google Scholar 

  25. Lok AS, McMahon BJ (2007) Chronic hepatitis B. Hepatology 45:507–539

    Article  PubMed  CAS  Google Scholar 

  26. Kim ES, Seoh YS, Lee KG et al (2008) Hepatitis B virus DNA level is a significant predictive factor for hepatitis B virus reactivation in inactive HBs antigen carriers. Korean J Hepatol 14:88

    Google Scholar 

  27. Liaw YF (1998) Hepatitis viruses under immunosuppressive agents. J Gastroenterol Hepatol 13:14–20

    Article  PubMed  CAS  Google Scholar 

  28. Nathan DM, Angus PW, Gibson PR (2006) Hepatitis B and C virus infections and anti-tumor necrosis factor-alpha therapy: guidelines for clinical approach. J Gastroenterol Hepatol 21:1366–1371

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, South Korea (#A102065). All authors declare that they have no proprietary, commercial, or financial interests that could be construed to have inappropriately influenced this study.

Disclosures

None.

Author information

Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-No, Jongno-Gu, Seoul, 110-744, South Korea

    Han Hee Ryu, Eun Young Lee, Kichul Shin, In Ah Choi, Eun Bong Lee & Yeong Wook Song

  2. Division or Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, 166 Gumi-Lo, Bundang-Gu, Sungnam-City, Gyeonggi-Do, South Korea

    Yun Jong Lee

  3. Division or Rheumatology, Department of Internal Medicine, University of Ulsan, Asan Medical Center, 88 Olympic-Lo 43-Gil, Songpa-gu, Seoul, South Korea

    Bin Yoo

  4. Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Yeonsei-Lo 50, Seodaemoon-Gu, Seoul, South Korea

    Min-Chan Park & Yong-Beom Park

  5. Division of Rheumatology, Department of Internal Medicine, Hanyang University Hospital, 17, Haengdang-dong, Seongdong-gu, Seoul, South Korea

    Sang-Cheol Bae

  6. Division of Rheumatology, Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine, 634-18, Geumam-dong, Deokjin-gu, Jeonju, Jeollabuk-do, South Korea

    Wan Hee Yoo

  7. Division of Rheumatology, Department of Internal Medicine, Pusan National University Hospital Institutes, 179, Guduk-Lo, Seo-gu, Busan, South Korea

    Sung Il Kim

Authors
  1. Han Hee Ryu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eun Young Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kichul Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. In Ah Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yun Jong Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bin Yoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Min-Chan Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yong-Beom Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sang-Cheol Bae
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Wan Hee Yoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sung Il Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Eun Bong Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Yeong Wook Song
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yeong Wook Song.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ryu, H.H., Lee, E.Y., Shin, K. et al. Hepatitis B virus reactivation in rheumatoid arthritis and ankylosing spondylitis patients treated with anti-TNFα agents: A retrospective analysis of 49 cases. Clin Rheumatol 31, 931–936 (2012). https://doi.org/10.1007/s10067-012-1960-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-012-1960-1

Keywords

Search

Navigation