Immunologic Research

, Volume 65, Issue 1, pp 257–261 | Cite as

Hepatitis B carrier state among SLE patients: case–control study

  • Omer Gendelman
  • Naim Mahroum
  • Doron Comaneshter
  • Pnina Rotman-Pikielny
  • Arnon D. Cohen
  • Howard Amital
  • Michael Sherf
Therapeutic Aspects in Autoimmunity


The association between hepatitis B and autoimmune disorders has been intriguing for decades. Many reports have speculated on the possible linkage between these two conditions, yet never before data driven from a large national database was utilized in order to investigate this issue. The objective of this study was to investigate the association between SLE and hepatitis B carrier state. Patients with SLE were compared with age- and sex-matched controls regarding the proportion of hepatitis B carrier state in a case–control study. Chi-square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. The study included 5018 lupus patients over the age of 20 years and 25,090 age- and sex-frequency-matched controls without SLE. The proportion of hepatitis B carriers was higher in SLE patients as compared to controls (0.9 and 0.56 %, respectively; p < 0.001). A significant association was also observed among patients in lower socioeconomic status. In a multivariate logistic regression analysis, SLE was significantly associated with hepatitis B (OR = 1.828, 95 % CI = 1.291–2.590). Patients with SLE have a greater proportion of hepatitis B carrier state than matched controls.


SLE Hepatitis B Autoimmune disease Carrier Infections 


  1. 1.
    Borchers AT, Naguwa SM, Shoenfeld Y, Gershwin ME. The geoepidemiology of systemic lupus erythematosus. Autoimmun Rev. 2010;9(5):A277–87.CrossRefPubMedGoogle Scholar
  2. 2.
    Borchers AT, Leibushor N, Naguwa SM, Cheema GS, Shoenfeld Y, Gershwin ME. Lupus nephritis: a critical review. Autoimmun Rev. 2012;12(2):174–94.CrossRefPubMedGoogle Scholar
  3. 3.
    Danchenko N, Satia JA, Anthony MS. Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden. Lupus. 2006;15(5):308–18.CrossRefPubMedGoogle Scholar
  4. 4.
    Ingvarsson RF, Bengtsson AA, Jönsen A. Variations in the epidemiology of systemic lupus erythematosus in southern Sweden. Lupus. 2016. doi: 10.1177/0961203316635288.PubMedGoogle Scholar
  5. 5.
    Pons-Estel GJ, Alarcon GS, Scofield L, Reinlib L, Cooper GS. Understanding the epidemiology and progression of systemic lupus erythematosus. Semin Arthritis Rheum. 2010;39(4):257–68.CrossRefPubMedGoogle Scholar
  6. 6.
    Guy A, Tiosano S, Comaneshter D, Tekes-Manova D, Shovman O, Cohen AD et al. Aortic aneurysm association with SLE - a case-control study. Lupus. 2016. doi: 10.1177/0961203316628999.PubMedGoogle Scholar
  7. 7.
    Petri M. Epidemiology of systemic lupus erythematosus. Best Pract Res Clin Rheumatol. 2002;16(5):847–58.CrossRefPubMedGoogle Scholar
  8. 8.
    Dienstag JL. Hepatitis B virus infection. N Engl J Med. 2008;359(14):1486–500.CrossRefPubMedGoogle Scholar
  9. 9.
    Ganem D, Prince AM. Hepatitis B virus infection—natural history and clinical consequences. N Engl J Med. 2004;350(11):1118–29.CrossRefPubMedGoogle Scholar
  10. 10.
    Merrill RM, Hunter BD. Seroprevalence of markers for hepatitis B viral infection. Int J Infect Dis. 2011;15(2):e78–121.CrossRefPubMedGoogle Scholar
  11. 11.
    Yim HJ, Lok AS. Natural history of chronic hepatitis B virus infection: what we knew in 1981 and what we know in 2005. Hepatology. 2006;43(2 Suppl 1):S173–81.CrossRefPubMedGoogle Scholar
  12. 12.
    Bar-Shany S, Green MS, Slepon R, Gilon E. Ethnic differences in the prevalence of hepatitis B surface antigen among Israeli blood donors: changes between 1972 and 1988. Int J Epidemiol. 1991;20(1):271–5.CrossRefPubMedGoogle Scholar
  13. 13.
    Bogomolski-Yahalom V, Granot E, Linder N, Adler R, Korman S, Manny N, et al. Prevalence of HBsAg carriers in native and immigrant pregnant female populations in Israel and passive/active vaccination against HBV of newborns at risk. J Med Virol. 1991;34(4):217–22.CrossRefPubMedGoogle Scholar
  14. 14.
    El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118–27.CrossRefPubMedGoogle Scholar
  15. 15.
    Bonafede RP, van Staden M, Klemp P. Hepatitis B virus infection and liver function in patients with systemic lupus erythematosus. J Rheumatol. 1986;13(6):1050–2.PubMedGoogle Scholar
  16. 16.
    Chen X, Hong L, Zhang W, Yuan M, Yang Q, Mao H, et al. Hepatitis B Virus infection rate and distribution in Chinese systemic lupus erythematosus patients. Med Sci Monit. 2015;21:1955–9.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Lai KN, Lai FM, Lo S, Leung A. Is there a pathogenetic role of hepatitis B virus in lupus nephritis? Arch Pathol Lab Med. 1987;111(2):185–8.PubMedGoogle Scholar
  18. 18.
    Marinchev L, Antonov K, Peytcheva V, Kolarov Z. Outcome in a patient with systemic lupus erythematosus and concurrent chronic hepatitis B infection. BMJ Case Rep. 2010;2010. doi: 10.1136/bcr.09.2009.2273.CrossRefGoogle Scholar
  19. 19.
    Shorey J, Cheatum DE, Combes B, Ziff M. Hepatitis B antigen and antibody in patients with systemic lupus erythematosus. Arthritis Rheum. 1974;17(5):583–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Wang Z, Li M, Zeng X, Liu X. Hepatitis B virus-associated antigen deposition in renal tissue from patients with systemic lupus erythematosus. J Rheumatol. 2012;39(5):974–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Zhao J, Qiu M, Li M, Lu C, Gu J. Low prevalence of hepatitis B virus infection in patients with systemic lupus erythematosus in southern China. Rheumatol Int. 2010;30(12):1565–70.CrossRefPubMedGoogle Scholar
  22. 22.
    Bieber V, Cohen AD, Freud T, Agmon-Levin N, Gertel S, Amital H. Autoimmune smoke and fire—coexisting rheumatoid arthritis and chronic obstructive pulmonary disease: a cross-sectional analysis. Immunol Res. 2013;56(2–3):261–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Farhi A, Cohen AD, Shovman O, Comaneshter D, Amital H, Amital D. Bipolar disorder associated with rheumatoid arthritis: a case-control study. J Affect Disord. 2016;189:287–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Houri LE, Watad A, Whitby A, Tiosano S, Comaneshter D, Cohen AD, et al. Coexistence of ischemic heart disease and rheumatoid arthritis patients—a case control study. Autoimmun Rev. 2016;15(4):393–6.CrossRefGoogle Scholar
  25. 25.
    Saeki Y, Ishihara K. Infection-immunity liaison: pathogen-driven autoimmune-mimicry (PDAIM). Autoimmun Rev. 2014;13(10):1064–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Palazzi C, Buskila D, D’Angelo S, D’Amico E, Olivieri I. Autoantibodies in patients with chronic hepatitis C virus infection: pitfalls for the diagnosis of rheumatic diseases. Autoimmun Rev. 2012;11(9):659–63.CrossRefPubMedGoogle Scholar
  27. 27.
    Marcos M, Alvarez F, Brito-Zeron P, Bove A, Perez-De-Lis M, Diaz-Lagares C, et al. Chronic hepatitis B virus infection in Sjogren’s syndrome. Prevalence and clinical significance in 603 patients. Autoimmun Rev. 2009;8(7):616–20.CrossRefPubMedGoogle Scholar
  28. 28.
    Berkun Y, Zandman-Goddard G, Barzilai O, Boaz M, Sherer Y, Larida B, et al. Infectious antibodies in systemic lupus erythematosus patients. Lupus. 2009;18(13):1129–35.CrossRefPubMedGoogle Scholar
  29. 29.
    Doaty S, Agrawal H, Bauer E, Furst DE. Infection and lupus: Which causes which? Curr Rheumatol Rep. 2016;18(3):13.CrossRefPubMedGoogle Scholar
  30. 30.
    James WH. A potential explanation of the reported low prevalence of hepatitis B virus infection in patients with systemic lupus erythematosus. Rheumatol Int. 2012;32(3):835.CrossRefPubMedGoogle Scholar
  31. 31.
    Vergani D, Mieli-Vergani G. Autoimmune manifestations in viral hepatitis. Semin Immunopathol. 2013;35(1):73–85.CrossRefPubMedGoogle Scholar
  32. 32.
    Yamashita H, Shimizu A, Tsuchiya H, Takahashi Y, Kaneko H, Kano T, et al. Chronic active Epstein-Barr virus infection mimicking autoimmune hepatitis exacerbation in a patient with systemic lupus erythematosus. Lupus. 2014;23(8):833–6.CrossRefPubMedGoogle Scholar
  33. 33.
    Zafrir Y, Agmon-Levin N, Paz Z, Shilton T, Shoenfeld Y. Autoimmunity following hepatitis B vaccine as part of the spectrum of ‘Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants’ (ASIA): analysis of 93 cases. Lupus. 2012;21(2):146–52.CrossRefPubMedGoogle Scholar
  34. 34.
    Zandman-Goddard G, Berkun Y, Barzilai O, Boaz M, Blank M, Ram M, et al. Exposure to Epstein-Barr virus infection is associated with mild systemic lupus erythematosus disease. Ann NY Acad Sci. 2009;1173:658–63.CrossRefPubMedGoogle Scholar
  35. 35.
    Doria A, Sarzi-Puttini P, Shoenfeld Y. Infections, rheumatism and autoimmunity: the conflicting relationship between humans and their environment. Autoimmun Rev. 2008;8(1):1–4.CrossRefPubMedGoogle Scholar
  36. 36.
    Aytac MB, Kasapcopur O, Aslan M, Erener-Ercan T, Cullu-Cokugras F, Arisoy N. Hepatitis B vaccination in juvenile systemic lupus erythematosus. Clin Exp Rheumatol. 2011;29(5):882–6.PubMedGoogle Scholar
  37. 37.
    Chng HH, Fock KM, Chew CN, Guan R, Feng PH, Boey ML, et al. Hepatitis B virus infection in patients with systemic lupus erythematosus. Singap Med J. 1993;34(4):325–6.Google Scholar
  38. 38.
    Ram M, Shoenfeld Y. Hepatitis B: infection, vaccination and autoimmunity. Isr Med Assoc J. 2008;10(1):61–4.PubMedGoogle Scholar
  39. 39.
    Soylu S, Gul U, Gonul M, Kilic A, Cakmak SK, Demiriz M. An uncommon presentation of the co-existence of morphea and vitiligo in a patient with chronic hepatitis B virus infection: Is there a possible association with autoimmunity? Am J Clin Dermatol. 2009;10(5):336–8.CrossRefPubMedGoogle Scholar
  40. 40.
    Watanabe R, Ishii T, Nakamura K, Shirai T, Tajima Y, Fujii H, et al. Prevalence and time course of hepatitis B virus infection in patients with systemic lupus erythematosus under immunosuppressive therapy. Mod Rheumatol. 2013;23(6):1094–100.CrossRefPubMedGoogle Scholar
  41. 41.
    Looi LM, Prathap K. Hepatitis B virus surface antigen in glomerular immune complex deposits of patients with systemic lupus erythematosus. Histopathology. 1982;6(2):141–7.CrossRefPubMedGoogle Scholar
  42. 42.
    Ram M, Anaya JM, Barzilai O, Izhaky D, Katz BSP, Blank M, et al. The putative protective role of hepatitis B virus (HBV) infection from autoimmune disorders. Autoimmun Rev. 2008;7(8):621–5.CrossRefPubMedGoogle Scholar
  43. 43.
    Lu CL, Tsai ST, Chan CY, Hwang SJ, Tsai CY, Wu JC, et al. Hepatitis B infection and changes in interferon-alpha and -gamma production in patients with systemic lupus erythematosus in Taiwan. J Gastroenterol Hepatol. 1997;12(4):272–6.CrossRefPubMedGoogle Scholar
  44. 44.
    Mercado U, Avendano-Reyes M, Araiza-Casillas R, Diaz-Molina R. Prevalance of antibodies against hepatitis C and B viruses in patients with systemic lupus erythematosus. Rev Gastroenterol Mex. 2005;70(4):399–401.PubMedGoogle Scholar
  45. 45.
    Abu-Shakra M, El-Sana S, Margalith M, Sikuler E, Neumann L, Buskila D. Hepatitis B and C viruses serology in patients with SLE. Lupus. 1997;6(6):543–4.CrossRefPubMedGoogle Scholar
  46. 46.
    Alarcon-Segovia D, Fishbein E, Diaz-Jouanen E. Presence of hepatitis-associated antigen in systemic lupus erythematosus. Clin Exp Immunol. 1972;12(1):9–19.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Permin H, Aldershvile J, Nielsen JO. Hepatitis B virus infection in patients with rheumatic diseases. Ann Rheum Dis. 1982;41(5):479–82.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Takahashi T, de la Garza L, Ponce-de-Leon S, Palacios-Macedo A, Contreras JL, Sanchez-Guerrero J, et al. Risk factors for operative morbidity in patients with systemic lupus erythematosus: an analysis of 63 surgical procedures. Am Surg. 1995;61(3):260–4.PubMedGoogle Scholar
  49. 49.
    Pagliaccetti NE, Robek MD. Interferon-lambda in the immune response to hepatitis B virus and hepatitis C virus. J Interferon Cytokine Res. 2010;30(8):585–90.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Meyer O. Interferon-alpha as a treatment target in systemic lupus erythematosus. Jt Bone Spine. 2012;79(2):113–6.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Omer Gendelman
    • 1
    • 2
  • Naim Mahroum
    • 1
    • 2
  • Doron Comaneshter
    • 3
  • Pnina Rotman-Pikielny
    • 4
  • Arnon D. Cohen
    • 3
    • 5
  • Howard Amital
    • 1
    • 2
  • Michael Sherf
    • 6
    • 7
  1. 1.Department of Medicine ‘B’, Zabludowicz Center for Autoimmune DiseasesSheba Medical CenterTel-HashomerIsrael
  2. 2.Sackler Faculty of MedicineTel-Aviv UniversityTel Aviv-YafoIsrael
  3. 3.Siaal Research Center for Family Medicine and Primary Care, Faculty of Health SciencesBen Gurion University of the NegevBeer ShevaIsrael
  4. 4.Metabolic Bone Disease ServiceMeir Medical CenterKfar-SabaIsrael
  5. 5.Chief Physician’s OfficeClalit Health ServicesTel AvivIsrael
  6. 6.Central ManagementClalit Health ServicesTel AvivIsrael
  7. 7.Department of Public Health, Faculty of Health SciencesBen-Gurion University of NegevBeer ShevaIsrael

Personalised recommendations