The Frequency of Chronic and Occult Hepatitis B Infection in the Patients Receiving Biological DMARD Therapy and Treatment Management

Abstract

Aim: We aimed to investigate the presence of hepatitis B virus (HBV) reactivation, chronic and occult HBV in patients who are followed in the Physical Medicine and Rehabilitation Clinic of Zonguldak Bülent Ecevit University Health Practice Research Hospital and using biological disease modifying drugs (bDMARDs). Material and Methods: The data files of the patients with ongoing biological disease-modifying antirheumatic drug (bDMARD) therapy that was followed by the Physical Medicine and Rehabilitation Clinic were analyzed retrospectively. Patient data such as age, gender, diagnosis, medication and its duration, Hepatitis B antigens and antibodies (HBsAg, anti-HBs and anti-HBc IgG), and antiviral HBV treatments were recorded. Results: The study included 138 patients comprising 64 (46.4%) females and 74 (53.6%) males. The mean age was 47.7±11.9 years. HBsAg, anti-HBc IgG, and anti-HBs positivity were detected in 4 (2.9%), 47 (34.8%), and 63 (45.6%) patients in our outpatient clinic, respectively. Thirty-two (23.2%) of the patients were receiving antiviral treatment. Close HBV DNA monitoring was performed for 3 months in 15 patients with (+) anti-HBc IgG, these patients were not followed by antiviral treatment. Totally 16 patients were vaccinated against Hepatitis B. Conclusion: As a consequence of the study, no HBV reactivation was encountered in the clinical follow-up of 47 patients with an ongoing medication of meanly 5 years for chronic and occult HBV. We concluded that the development of a feared complication such as HBV reactivation can be prevented in patients using bDMARDs with strict follow-up and appropriate protocol

Keywords

• Anti-tumor necrosis factor therapy
• Biological DMARD
• Hepatitis B virus reactivation
• Rheumatic disease

Biyolojik DMARD Kullanan Hastalarda Kronik Hepatit B Enfeksiyonu ve Okkült Hepatit B Sıklığı ve Tedavi Yönetimi

Abstract

Amaç: Biyolojik hastalık modifiye edici ilaç (bDMARDs) kullanan hastaların (romatoid artrit, ankilozan spondilit ve psöriatik artrit) Hepatit B virüs (HBV) reaktivasyonu, kronik ve okkült HBV varlığını araştırmayı hedefledik. Gereç ve Yöntemler: Zonguldak Bülent Ecevit Üniversitesi Sağlık Uygulama Araştırma Hastanesi Fiziksel Tıp ve Rehabilitasyon kliniğinde takip edilen ve biyolojik DMARDs (infliksimab, adalimumab, etanercept, golimumab, sertolizumab, tofasitinib, sekukinumab, tosilizumab, ustekinumab) kullanan hastaların dosyalarında yer alan verileri retrospektif olarak incelendi. Hastaların yaşı, cinsiyeti, tanıları (romatoid artrit, ankilozan spondilit ve psöriatik artrit), kullanmakta olduğu ilaçlar, kullanım süreleri, Hepatit B antijen ve antikorları (HBsAg, anti-HBs ve anti-HBc IgG) ve HBV için ilaç kullanmakta olan hastalar kaydedildi. Bulgular: Çalışmaya 138 hasta dahil edildi. Hastaların 64’ü (%46,4) kadın ve 74’ü (%53,6) erkekti. Ortalama yaşları 47,7±11,9 yıl olarak hesaplandı. Olguların dördünde (%2,9) HBsAg 47 (%34,8)’sinde anti-HBc IgG ve 63 (%45,6)’ünde anti-HBs pozitifliği vardı. Hastaların 32 (%23,2)’si antiviral tedavi almaktaydı. Anti HBc-Ig G(+) olan 15 (%10,8) olgu antiviral tedavisizdi ve üç aylık HBV DNA izlemleri ile takip edilmekteydi. Toplam 16 (%11,5) olgu Hepatit B’ye karşı aşılıydı. Sonuç: Çalışma sonucunda bDMARD kullanan kronik ve okkült HBV yönünden 47 olgunun ortalama beş yıllık tedavi ve klinik izleminde HBV reaktivasyonu görülmedi. Biyolojik DMARDs kullananlarda sıkı takip ve uygun protokolle HBV reaktivasyonu gibi korkulan bir komplikasyon gelişmeyebilir.

Keywords

• Anti-tümor nekrozis faktör tedavi
• Biyolojik DMARD
• Hepatit B reaktivasyon
• Romatizmal Hastalıklar

References

1. 1. Willrich MAV et al. Tumor necrosis factor inhibitors: clinical utility in autoimmune diseases. Transl Res 2015;165(2):270-82.
2. 2. Ömer Karadağ et al. Guideline of the viral hepatitis screening before biologic agents use in patients with rheumatic diseases. RAED Journal 2015;7(1):28–32.
3. 3. Loomba R, Liang TJ. Hepatitis B reactivation associated with immune suppressive and biological modifier therapies: Current concepts, management strategies, and future directions. Basic and Clinical Gastroenterology and Hepatology 2017;152(6):1297-1309.
4. 4. Tozun N et al. Seroprevalence of hepatitis B and C virus infections and risk factors in Turkey: a fieldwork TURHEP study. Clin Microbiol Infect 2015;21:1020–1026.
5. 5. Pay S. The use of Anti-TNF drugs in rheumatic disorders: Medical education. Turkiye Klinikleri J Med Sci 2006;26(4):430-40.
6. 6. Terrault NA et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018;67(4):1560-1599.
7. 7. Michel M et al. Fulminant hepatitis after infliximab in a patient with hepatitis B virus treated for an adult onset Still's disease. J Rheumatol 2003;30(7):1624-1625.
8. 8. Ostuni P et al. Hepatitis B reactivation in a chronic hepatitis B surface antigen carrier with rheumatoid arthritis treated with infliximab and low dose methotrexate. Ann Rheum Dis 2003;62(7):686-687.

9. 9. Lee YH et al. Hepatitis B virus reactivation in HBsAg-positive patients with rheumatic diseases undergoing anti-tumor necrosis factor therapy or DMARDs. Int J Rheum Dis 2013;16:527–531.
10. 10. Wong GH, Goeddel DV. Tumour necrosis factors alpha and beta inhibit virüs replication and synergize with interferons. Nature 1986; 323:819–22
11. 11. Ganem D, Prince AM. Hepatitis B virus infection-natural history and clinical consequences. N Engl J Med 2004;350(11):1118-1129.
12. 12. Carroll MB, Forgione MA. Use of tumor necrosis factor α inhibitors in hepatitis B surface antigen-positive patients: A literature review and potential mechanisms of action. Clin Rheumatol 2010;29(9):1021-9.
13. 13. Lee YH et al. Hepatitis B virus (HBV) reactivation in rheumatic patients with hepatitis core antigen (HBV occult carriers) undergoing anti‐tumor necrosis factor therapy. Clin Exp Rheumatol 2013;31:118‐121
14. 14. Tamori A 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;46:556‐564.
15. 15. Oketani M et al. Prevention of hepatitis B virus reactivation in patients receiving immunosuppressive therapy or chemotherapy. Hepatol Res 2012;42:627‐636.
16. 16. Singh JA et al, 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis, American College of Rheumatology 2016;68(1):1-26.
17. 17. Vassilopoulos D et al. Long-term safety of anti-TNF treatment in patients with rheumatic diseases and chronic or resolved hepatitis B virus infection. Ann Rheum Dis 2010;69(7):1352-1355.
18. 18. Holroyd CR et al. The British Society for Rheumatology biologic DMARD safety guidelines in inflammatory arthritis. Rheumatology 2019;58(2):220-226.
19. 19. Watanabe R 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):129-133.
20. 20. Stine JG et al. Rheumatologists' awareness of and screening practices for hepatitis B virüs infection prior to initiating immunomodulatory therapy. Arthritis Care Res 2010;62(5):704-711.
21. 21. Toka B et al. Rheumatologists' awareness of hepatitis B reactivation before immunosuppressive therapy. Rheumatol Int 2019;39(12):2077-2085.
22. 22. Watanabe T et al. Incidence and risk factors for reactivation from resolved hepatitis B virus in rheumatoid arthritis patients treated with biological disease-modifying antirheumatic drugs. Int J Rheum Dis 2019;22(4):574-582
23. 23. Chen LF et al. Short-course tocilizumab increases risk of hepatitis B virus reactivation in patients with rheumatoid arthritis: a prospective clinical observation. Int J Rheum Dis 2017;20(7):859-869
24. 24. Lin TC et al. Risk of Hepatitis B virus reactivation in patients with inflammatory arthritis receiving disease-modifying antirheumatic drugs: A systematic review and meta-analysis. Arthritis Care Res 2018;70(5):724-731.