Skip to main content

Advertisement

SpringerLink
Log in

Chronic hepatitis B viral infection among RA patients—a cross-sectional control study

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

Abstract

Background and objectives

Rheumatoid arthritis (RA) is the most common inflammatory joint disorder presenting also with extra-articular manifestations. As many other autoimmune diseases, it has been suggested that infectious diseases might contribute to its emergence. Hepatitis viruses were suggested by several reports as a trigger of RA onset. We aimed to assess the association between RA and chronic hepatitis B viral infection (HBV).

Methods

Patients with RA were compared with age- and sex-matched controls regarding the proportion of chronic HBV infection in a case-control study. The chi-square and t tests were used for univariate analysis, whereas a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services.

Results

There was a significantly higher proportion of chronic HBV infection in RA patients compared with controls (1.19% vs 0.63%, respectively; p < 0.001). In a multivariate logistic regression analysis, RA was significantly associated with chronic HBV infection (OR = 1.89, 95%CI 1.55–2.29, p < 0.001).

Conclusions

Patients with RA have a greater proportion of chronic HBV infection than matched controls. Screening for HBV infection among RA patients may be warranted.

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

Similar content being viewed by others

References

  1. McInnes IB, Schett G (2011) The pathogenesis of rheumatoid arthritis. N Engl J Med 365(23):2205–2219. https://doi.org/10.1056/NEJMra1004965

    Article  CAS  PubMed  Google Scholar 

  2. Firestein GS (2003) Evolving concepts of rheumatoid arthritis. Nature 423(6937):356–361. https://doi.org/10.1038/nature01661

    Article  CAS  Google Scholar 

  3. Turesson C, O'Fallon WM, Crowson CS, Gabriel SE, Matteson EL (2003) Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years. Ann Rheum Dis 62(8):722–727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Myasoedova E, Crowson CS, Turesson C, Gabriel SE, Matteson EL (2011) Incidence of extraarticular rheumatoid arthritis in Olmsted County, Minnesota, in 1995–2007 versus 1985–1994: a population-based study. J Rheumatol 38(6):983–989

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, Spitz PW, Haga M, Kleinheksel SM, Cathey MA (1994) The mortality of rheumatoid arthritis. Arthritis Rheum 37(4):481–494

    Article  CAS  PubMed  Google Scholar 

  6. Solomon DH, Karlson EW, Rimm EB, Cannuscio CC, Mandl LA, Manson JE, Stampfer MJ, Curhan GC (2003) Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation 107(9):1303–1307

    Article  PubMed  Google Scholar 

  7. Guler-Yuksel M, Allaart CF, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, van Groenendael JH, Mallee C, de Bois MH, Breedveld FC, Dijkmans BA, Lems WF (2009) Changes in hand and generalised bone mineral density in patients with recent-onset rheumatoid arthritis. Ann Rheum Dis 68(3):330–336. https://doi.org/10.1136/ard.2007.086348

    Article  CAS  PubMed  Google Scholar 

  8. Choy E, Sattar N (2009) Interpreting lipid levels in the context of high-grade inflammatory states with a focus on rheumatoid arthritis: a challenge to conventional cardiovascular risk actions. Ann Rheum Dis 68(4):460–469. https://doi.org/10.1136/ard.2008.101964

    Article  CAS  PubMed  Google Scholar 

  9. Smitten AL, Simon TA, Hochberg MC, Suissa S (2008) A meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis. Arthritis Res Ther 10(2):R45. https://doi.org/10.1186/ar2404

    Article  PubMed  PubMed Central  Google Scholar 

  10. van Boekel MA, Vossenaar ER, van den Hoogen FH, van Venrooij WJ (2002) Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value. Arthritis Res 4(2):87–93. https://doi.org/10.1186/ar395

    Article  PubMed  Google Scholar 

  11. Doran MF, Crowson CS, Pond GR, O'Fallon WM, Gabriel SE (2002) Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheumatol 46(9):2287–2293

    Article  Google Scholar 

  12. Baum J (1971) Infection in rheumatoid arthritis. Arthritis Rheumatol 14(1):135–137

    Article  CAS  Google Scholar 

  13. Gendelman O, Mahroum N, Comaneshter D, Rotman-Pikielny P, Cohen AD, Amital H, Sherf M (2017) Hepatitis B carrier state among SLE patients: case-control study. Immunol Res 65(1):257–261. https://doi.org/10.1007/s12026-016-8834-6

    Article  CAS  PubMed  Google Scholar 

  14. Maya R, Gershwin ME, Shoenfeld Y (2008) Hepatitis B virus (HBV) and autoimmune disease. Clin Rev Allergy Immunol 34(1):85–102

    Article  PubMed  Google Scholar 

  15. Watad A, Azrielant S, Bragazzi NL, Sharif K, David P, Katz I, Aljadeff G, Quaresma M, Tanay G, Adawi M, Amital H, Shoenfeld Y (2017) Seasonality and autoimmune diseases: the contribution of the four seasons to the mosaic of autoimmunity. J Autoimmun 82:13–30. https://doi.org/10.1016/j.jaut.2017.06.001

    Article  CAS  PubMed  Google Scholar 

  16. Mahroum N, Hejly A, Tiosano S, Gendelman O, Comaneshter D, Cohen AD, Amital H (2017) Chronic hepatitis C viral infection among SLE patients: the significance of coexistence. Immunol Res 65(2):477–481. https://doi.org/10.1007/s12026-016-8886-7

    Article  CAS  PubMed  Google Scholar 

  17. Ramos-Casals M, Muñoz S, Medina F, Jara L-J, Rosas J, Calvo-Alen J, Brito-Zerón P, Forns X, Sánchez-Tapias J-M (2009) Systemic autoimmune diseases in patients with hepatitis C virus infection: characterization of 1020 cases (The HISPAMEC Registry). J Rheumatol 36(7):1442–1448

    Article  PubMed  Google Scholar 

  18. De Virgilio A, Greco A, Magliulo G, Gallo A, Ruoppolo G, Conte M, Martellucci S, de Vincentiis M (2016) Polyarteritis nodosa: a contemporary overview. Autoimmun Rev 15(6):564–570

    Article  PubMed  Google Scholar 

  19. Chen YL, Jing J, Mo YQ, Ma JD, Yang LJ, Chen LF, Zhang X, Yan T, Zheng DH, Pessler F, Dai L (2018) Presence of hepatitis B virus in synovium and its clinical significance in rheumatoid arthritis. Arthritis Res Ther 20(1):130. https://doi.org/10.1186/s13075-018-1623-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hsu CS, Lang HC, Huang KY, Lin HH, Chen CL (2016) Association of rheumatoid arthritis and hepatitis B infection: a nationwide nested case-control study from 1999 to 2009 in Taiwan. Medicine (Baltimore) 95(18):e3551

    Article  CAS  Google Scholar 

  21. World Health Organization (2017) Global Hepatitis Programme. Global hepatitis report, 2017

  22. Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, Moreland LW, O'Dell J, Winthrop KL, Beukelman T, Bridges SL, Chatham WW, Paulus HE, Suarez-almazor M, Bombardier C, Dougados M, Khanna D, King CM, Leong AL, Matteson EL, Schousboe JT, Moynihan E, Kolba KS, Jain A, Volkmann ER, Agrawal H, Bae S, Mudano AS, Patkar NM, Saag KG (2012) 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res 64(5):625–639

    Article  CAS  Google Scholar 

  23. Kanduc D, Shoenfeld Y (2016) From HBV to HPV: designing vaccines for extensive and intensive vaccination campaigns worldwide. Autoimmun Rev 15(11):1054–1061. https://doi.org/10.1016/j.autrev.2016.07.030

    Article  PubMed  Google Scholar 

  24. Watad A, Bragazzi NL, Adawi M, Aljadeff G, Amital H, Comaneshter D, Cohen AD, Amital D (2017) Anxiety disorder among rheumatoid arthritis patients: insights from real-life data. J Affect Disord 213:30–34. https://doi.org/10.1016/j.jad.2017.02.007

    Article  PubMed  Google Scholar 

  25. Watad A, Bragazzi NL, Tiosano S, Yavne Y, Comaneshter D, Cohen AD, Amital H (2018) Alzheimer’s disease in systemic sclerosis patients: a nationwide population-based cohort study. J Alzheimers Dis 65(1):117–124

    Article  PubMed  Google Scholar 

  26. Watad A, Tiosano S, Azrielant S, Whitby A, Comaneshter D, Cohen AD, Shoenfeld Y, Amital H (2017) Low levels of calcium or vitamin D - which is more important in systemic lupus erythematosus patients? An extensive data analysis. Clin Exp Rheumatol 35(1):108–112

    PubMed  Google Scholar 

  27. Watad A, Tiosano S, Yahav D, Comaneshter D, Shoenfeld Y, Cohen AD, Amital H (2017) Behcet’s disease and familial Mediterranean fever: two sides of the same coin or just an association? A cross-sectional study. Eur J Intern Med 39:75–78. https://doi.org/10.1016/j.ejim.2016.10.011

    Article  PubMed  Google Scholar 

  28. Dvir R, Sautto GA, Mancini N, Racca S, Diotti RA, Clementi M, Memoli M (2017) Autoimmune hepatitis and occult HCV infection: a prospective single-centre clinical study. Autoimmun Rev 16(3):323–325. https://doi.org/10.1016/j.autrev.2017.01.015

    Article  PubMed  Google Scholar 

  29. Tosato G, Steinberg AD, Blaese RM (1981) Defective EBV-specific suppressor T-cell function in rheumatoid arthritis. N Engl J Med 305(21):1238–1243

    Article  CAS  PubMed  Google Scholar 

  30. Wilder RL, Crofford LJ (1991) Do infectious agents cause rheumatoid arthritis? Clin Orthop Relat Res (265):36–41

  31. Balandraud N, Roudier J (2018) Epstein-Barr virus and rheumatoid arthritis. Joint Bone Spine 85(2):165–170. https://doi.org/10.1016/j.jbspin.2017.04.011

    Article  CAS  PubMed  Google Scholar 

  32. Listing J, Gerhold K, Zink A (2013) The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology 52(1):53–61

    Article  CAS  PubMed  Google Scholar 

  33. Singh JA, Cameron C, Noorbaloochi S, Cullis T, Tucker M, Christensen R, Ghogomu ET, Coyle D, Clifford T, Tugwell P, Wells GA (2015) Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis. Lancet 386(9990):258–265. https://doi.org/10.1016/s0140-6736(14)61704-9

    Article  PubMed  PubMed Central  Google Scholar 

  34. Alpert E, Isselbacher KJ, Schur PH (1971) The pathogenesis of arthritis associated with viral hepatitis: complement-component studies. N Engl J Med 285(4):185–189

    Article  CAS  PubMed  Google Scholar 

  35. Dienstag JL (1981) Hepatitis B as an immune complex disease. Semin Liver Dis 1(1):45–57. https://doi.org/10.1055/s-2008-1063929

    Article  CAS  PubMed  Google Scholar 

  36. Cacoub P, Saadoun D, Bourlière M, Khiri H, Martineau A, Benhamou Y, Varastet M, Pol S, Thibault V, Rotily M (2005) Hepatitis B virus genotypes and extrahepatic manifestations. J Hepatol 43(5):764–770

    Article  CAS  PubMed  Google Scholar 

  37. Lin TC, Hashemi N, Kim SC, Yang YK, Yoshida K, Tedeschi S, Desai R, Solomon DH (2018) Practice pattern of hepatitis B testing in rheumatoid arthritis patients: a cross-national comparison between the US and Taiwan. Arthritis Care Res (Hoboken) 70(1):30–38. https://doi.org/10.1002/acr.23241

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  39. Tamori A, Koike T, Goto H, Wakitani S, Tada M, Morikawa H, Enomoto M, Inaba M, Nakatani T, Hino M (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(4):556–564

    Article  CAS  PubMed  Google Scholar 

  40. Lahiri M, Dixon WG (2015) Risk of infection with biologic antirheumatic therapies in patients with rheumatoid arthritis. Best Pract Res Clin Rheumatol 29(2):290–305

    Article  PubMed  Google Scholar 

  41. Jeong H, Baek SY, Kim SW, Eun YH, Kim IY, Kim H, Lee J, Koh E-M, Cha H-S (2017) Comorbidities of rheumatoid arthritis: results from the Korean National Health and Nutrition Examination Survey. PLoS One 12(4):e0176260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine ‘B’, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, 52621, Tel-Hashomer, Israel

    Naim Mahroum, Abdulla Watad, Shmuel Tiosano, Ashraf Hejly, Hussein Mahagna & Howard Amital

  2. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Naim Mahroum, Abdulla Watad, Shmuel Tiosano, Roy Waknin & Howard Amital

  3. Chief Physician’s Office, Clalit Health Services Tel Aviv, Tel-Aviv, Israel

    Doron Comaneshter & Arnon D. Cohen

  4. Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel

    Arnon D. Cohen

Authors
  1. Naim Mahroum
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abdulla Watad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shmuel Tiosano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ashraf Hejly
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hussein Mahagna
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Roy Waknin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Doron Comaneshter
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Arnon D. Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Howard Amital
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Howard Amital.

Ethics declarations

The study was approved by the ethical committee of CHS, located at the Soroka Medical Center, Beer-Sheva, Israel.

Conflict of interest

Naim Mahroum- no conflict of interests.

Abdulla Watad - no conflict of interests.

Shmuel Tiosano - no conflict of interests.

Ashraf Hejly - no conflict of interests.

Hussein Mahagna - no conflict of interests.

Roy Waknin - no conflict of interests.

Doron Comaneshter - no conflict of interests.

Arnon Cohen received research grants from Janssen, Novartis, AbbVie, and Sanofi. Other relationships: In the last 3 years, Prof. Arnon Cohen served as a consultant, advisor, or speaker to AbbVie; Amgen; Boehringer Ingelheim; Dexcel pharma; Janssen; Kamedis; Lilly; Neopharm; Novartis; Perrigo; Pfizer, Rafa, Sanofi, Sirbal; Taro.

Howard Amital- received research grants from Janssen, Novartis, AbbVie and Pfizer. Other relationships: In the last 3 years Howard Amital served as a consultant, advisor or speaker to AbbVie; Boehringer Ingelheim; Janssen; Neopharm; Novartis; Perrigo; Pfizer, Rafa, Sanofi, Sanofi, Taro, Roche.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mahroum, N., Watad, A., Tiosano, S. et al. Chronic hepatitis B viral infection among RA patients—a cross-sectional control study. Clin Rheumatol 38, 1237–1241 (2019). https://doi.org/10.1007/s10067-019-04448-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-019-04448-x

Keywords

Search

Navigation