Araştırma Makalesi
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Evaluation of HBV Reactivation and Antiviral Prophylaxis in Patients Receiving Immunosuppressive Therapy

Yıl 2023, Cilt: 13 Sayı: 5, 809 - 813, 30.09.2023
https://doi.org/10.16899/jcm.1343166

Öz

Aim: Patients with chronic hepatitis B and people with a history of hepatitis B (HBV) infection are at risk of HBV reactivation (HBVr) when they receive immunosuppressive therapy. In this study, we aimed to evaluate the hepatitis B serology, risk groups and antiviral prophylaxis of patients receiving various immunosuppressive therapies due to rheumatological diseases.
Material and Method: The study included 375 patients over 18 years of age who received tumor necrosis factor-α (TNF-α) inhibitor, tyrosine kinase inhibitor, steroids, methotrexate or anti-CD20 antibodies due to rheumatic diseases in a training and research hospital between May 2022 and May 2023. Hepatitis B surface antigen (HbsAg), hepatitis B surface antibody (anti-Hbs), hepatitis B core protein antibody (anti-Hbc IgG) serologies, immunosuppressive therapies and oral antivirals were retrospectively analyzed.
Results: The average age of the 375 patients included in the study was 43.77±13.07 years. 193 (51.5%) of the patients were male. 11 patients were HbsAg positive, 150 patients were anti-Hbs positive, 19 patients were isolated anti-Hbc IgG positive, and 79 patients were both anti-Hbs and anti-Hbc IgG positive. According to serological findings, 109 (29%) patients had HBV exposure. All three test results of 194 (51.7%) patients were negative. A total of 85 (22.7%) patients received oral antiviral prophylaxis due to the use of immunosuppressive agents. In terms of HBVr, 16.5% were evaluated as high risk, 75.3% as moderate risk, and 8.2% as low risk. Out of 85 patients 79 received entecavir, 5 reveived tenofovir disoproxil fumarate (TDF) and 1 received tenofovir alafenamide fumarate (TAF). The mean duration for the immunosuppressive therapy was 6.41±4.20 years. The mean duration of oral antiviral prophylaxis among patients was 1.02±1.72 years. HBVr was not observed in any of our patients.
Conclusion: Before patients receive immunosuppressive therapy, hepatitis B serologies and prophylaxis indication should be evaluated firstly. In addition, as a preventive medicine activity, hepatitis B vaccinations of unvaccinated patients should be completed as quickly as possible.

Destekleyen Kurum

No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

Teşekkür

We thank the physicians of the rheumatology clinic.

Kaynakça

  • 1. Sono S, Sae-Chan J, Kaewdech A, Chamroonkul N, Sripongpun P. HBV seroprevalence and liver fibrosis status among population born before national immunization in Southern Thailand: Findings from a health check-up program. PLoS One. 2022;17(6):e0270458.
  • 2. Tozun N, Ozdogan O, Cakaloglu Y, Idilman R, Karasu Z, Akarca U, et al. Seroprevalence of hepatitis B and C virus infections and risk factors in Turkey: a fieldwork TURHEP study. Clin Microbiol Infect. 2015;21(11):1020-6.
  • 3. Wu T, Li J, Shao L, Xin J, Jiang L, Zhou Q, et al. Development of diagnostic criteria and a prognostic score for hepatitis B virus-related acute-on-chronic liver failure. Gut. 2018;67(12):2181-91.
  • 4. Reddy KR, Beavers KL, Hammond SP, Lim JK, Falck-Ytter YT. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148(1):215-9; quiz e16-7.
  • 5. Fukuda W, Hanyu T, Katayama M, Mizuki S, Okada A, Miyata M, et al. Risk stratification and clinical course of hepatitis B virus reactivation in rheumatoid arthritis patients with resolved infection: final report of a multicenter prospective observational study at Japanese Red Cross Hospital. Arthritis Research & Therapy. 2019;21(1):255.
  • 6. Mahroum N, Watad A, Tiosano S, Hejly A, Mahagna H, Waknin R, et al. Chronic hepatitis B viral infection among RA patients-a cross-sectional control study. Clin Rheumatol. 2019;38(5):1237-41.
  • 7. Etienne S, Vosbeck J, Bernsmeier C, Osthoff M. Prevention of Hepatitis B Reactivation in Patients Receiving Immunosuppressive Therapy: a Case Series and Appraisal of Society Guidelines. J Gen Intern Med. 2023;38(2):490-501.
  • 8. Aygen B, Demir AM, Gümüş M, Karabay O, Kaymakoğlu S, Köksal A, et al. Immunosuppressive therapy and the risk of hepatitis B reactivation: Consensus report. Turk J Gastroenterol. 2018;29(3):259-69.
  • 9. Pattullo V. Prevention of Hepatitis B reactivation in the setting of immunosuppression. Clin Mol Hepatol. 2016;22(2):219-37.
  • 10. Karadağ Ö, Kaşifoğlu T, Özer B, Kaymakoğlu S, Kuş Y, İnanç M, et al. Viral hepatitis screening guideline before biological drug use in rheumatic patients. Eur J Rheumatol. 2016;3(1):25-8.
  • 11. Cabalak M, Bal T, Ocak S. İmmünsüpresif Tedavi Alacak Hastalarda Hepatit Serolojisi. Harran Üniversitesi Tıp Fakültesi Dergisi. 2020;17.
  • 12. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370-98.
  • 13. Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560-99.
  • 14. Lau G, Yu ML, Wong G, Thompson A, Ghazinian H, Hou JL, et al. APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy. Hepatol Int. 2021;15(5):1031-48.
  • 15. Ceylan M, TURKEN M, Singil S, Pelin A, Şükran K. İmmunsupresif Tedavi Alan Hastalarda Hepatit B Reaktivasyonu Riskinin Değerlendirilmesi. İzmir Tıp Fakültesi Dergisi.1(3):112-6.
  • 16. Durak S, Coşar AM. Evaluation of the safety and antiviral efficacy of the tenofovir alafenamide fumarate molecule in immunosuppressed patients. Journal of Health Sciences and Medicine. 2022;5(6):1688-92.
  • 17. Jeong S, Shin HP, Kim HI. Real-World Single-Center Comparison of the Safety and Efficacy of Entecavir, Tenofovir Disoproxil Fumarate, and Tenofovir Alafenamide in Patients with Chronic Hepatitis B. Intervirology. 2022;65(2):94-103.
  • 18. Baranek B, Wang S, Cheung AM, Mishra S, Tan DH. The effect of tenofovir disoproxil fumarate on bone mineral density: a systematic review and meta-analysis. Antivir Ther. 2020;25(1):21-32.
  • 19. Ha NB, Ku K, Ha NB, Chaung KT, Trinh HN, Nguyen MH. Renal Function in Chronic Hepatitis B Patients Treated With Tenofovir Disoproxil Fumarate or Entecavir Monotherapy: A Matched Case-Cohort Study. J Clin Gastroenterol. 2015;49(10):873-7.
  • 20. Su J, Long L, Zou K. Antiviral prophylaxis for preventing reactivation of hepatitis B virus in rheumatic patients: a systematic review and meta-analysis. Clin Rheumatol. 2018;37(12):3201-14.
  • 21. Picardi M, Della Pepa R, Giordano C, Zacheo I, Pugliese N, Mortaruolo C, et al. Tenofovir vs lamivudine for the prevention of hepatitis B virus reactivation in advanced-stage DLBCL. Blood. 2019;133(5):498-501.
  • 22. Yang C, Qin B, Yuan Z, Chen L, Zhou HY. Meta-analysis of prophylactic entecavir or lamivudine against hepatitis B virus reactivation. Ann Hepatol. 2016;15(4):501-11.
  • 23. Chen M-H, Chen M-H, Liu C-Y, Tsai C-Y, Huang D-F, Lin H-Y, et al. Hepatitis B Virus Reactivation in Rheumatoid Arthritis Patients Undergoing Biologics Treatment. The Journal of Infectious Diseases. 2016;215(4):566-73.
  • 24. Padovan M, Filippini M, Tincani A, Lanciano E, Bruschi E, Epis O, et al. Safety of Abatacept in Rheumatoid Arthritis With Serologic Evidence of Past or Present Hepatitis B Virus Infection. Arthritis Care Res (Hoboken). 2016;68(6):738-43.
  • 25. Vassilopoulos D, Delicha EM, Settas L, Andrianakos A, Aslanidis S, Boura P, et al. Safety profile of repeated rituximab cycles in unselected rheumatoid arthritis patients: a long-term, prospective real-life study. Clin Exp Rheumatol. 2016;34(5):893-900.
  • 26. Harigai M, Winthrop K, Takeuchi T, Hsieh TY, Chen YM, Smolen JS, et al. Evaluation of hepatitis B virus in clinical trials of baricitinib in rheumatoid arthritis. RMD Open. 2020;6(1).
  • 27. Lee YH, Bae SC, Song GG. 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(5):527-31.
  • 28. 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.
  • 29. Canzoni M, Marignani M, Sorgi ML, Begini P, Biondo MI, Caporuscio S, et al. Prevalence of Hepatitis B Virus Markers in Patients with Autoimmune Inflammatory Rheumatic Diseases in Italy. Microorganisms. 2020;8(11).
  • 30. Makvandi M, Noormandi Pour S, Teimoori A, Shokri S, Mahmoudvand S, Biparva Haghighi S, et al. Frequency of Hepatitis B Markers in Systemic Lupus Erythematosus Patients in Iran. Asian Pac J Cancer Prev. 2022;23(6):1921-6.
  • 31. Cabalak M, Kimyon G, Bal T. Frequency of Hepatitis B Virus Screening in Patients with Systemic Lupus Erythematosus. Mediterranean Journal of Infection Microbes and Antimicrobials. 2020;9.
  • 32. Yang S, Tian G, Cui Y, Ding C, Deng M, Yu C, et al. Factors influencing immunologic response to hepatitis B vaccine in adults. Sci Rep. 2016;6:27251. 33. Öztürk S, Kaçar M, Toprak S, Çolak O, Öztürk D, Agalar C. Hepatit B Aşılama Verileri; İmmünsüpresif Hastalarda Tek Doz mu? Çift Doz mu? Namık Kemal Tıp Dergisi.8(3):499-506.

İmmunsupresif Tedavi Alan Hastalarda HBV Reaktivasyonu ve Antiviral Profilaksinin Değerlendirilmesi

Yıl 2023, Cilt: 13 Sayı: 5, 809 - 813, 30.09.2023
https://doi.org/10.16899/jcm.1343166

Öz

Amaç: Kronik hepatit B’li hastalar ve geçirilmiş hepatit B virüs enfeksiyonu olan kişiler immünsupresif tedavi aldıkları zaman HBV reaktivasyonu riskine maruz kalırlar. Bu çalışmada romatolojik hastalıklar nedeni ile çeşitli immünsupresif tedavileri alan hastaların hepatit B serolojilerini, risk gruplarını ve antiviral profilaksi alma durumlarını sunmayı amaçladık.
Gereç ve Yöntem: Çalışmaya Mayıs 2022 ile Mayıs 2023 tarihleri arasında bir eğitim ve araştırma hastanesinde romatolojik hastalıklar nedeni ile tümör nekroz faktör-α inhibitörü, tirozin kinaz inhibitörü, steroid, metotreksat veya anti-CD20 antikoru alan 18 yaş üstü 375 hasta dahil edildi. Hastaların HbsAg, anti-Hbs ve anti-Hbc IgG serolojileri, immünsupresif tedavileri ve süresi ile almış oldukları oral antiviraller retrospektif olarak incelendi.
Bulgular: Çalışmaya alınan 375 hastanın yaş ortalaması 43.77±13.07 idi. Hastaların 193’ ü (%51.5) erkek idi. Hastaların 11’ inde HbsAg pozitif, 150’ sinde anti Hbs pozitif, 19’ unda izole anti-Hbc IgG pozitif ve 79 hastada ise anti-Hbs ile anti-Hbc IgG beraber pozitif idi. Serolojik bulgulara göre 109 (%29) hastada HBV ile karşılaşma durumu mevcuttu. 194 (%51.7) hastanın ise her üç tetkik sonucu da negatif idi. Toplamda 85 (%22.7) hasta immünsupresif ajan kullanımı nedeni ile oral antiviral profilaksi almaktaydı. HBV reaktivasyon riski profilaksi başlanan hastaların 14’ ünde (%16.5) yüksek, 64’ ünde (%75.3) orta, 7’ sinde (%8.2) düşük riskliydi. 79 hasta entekavir, 5 hasta tenofovir disoproksil fumarat ve 1 hasta ise tenofovir alafenamid fumarat almakta idi. Ortalama immünsüpresif tedavi alma süresi 6.41±4.20 yıl idi. Hastaların oral antiviral profilaksi alma süreleri ise ortalama 1.02±1.72 yıl idi. HBV reaktivasyonu görülen hastamız olmadı.
Sonuç: Hastalar immünsupresif tedavi almadan önce hepatit B serolojileri ve profilaksi durumları öncelikle değerlendirilmelidir. Ayrıca koruyucu hekimlik faaliyeti olarak aşısız hastaların en kısa sürede hepatit B aşıları tamamlanmalıdır.

Kaynakça

  • 1. Sono S, Sae-Chan J, Kaewdech A, Chamroonkul N, Sripongpun P. HBV seroprevalence and liver fibrosis status among population born before national immunization in Southern Thailand: Findings from a health check-up program. PLoS One. 2022;17(6):e0270458.
  • 2. Tozun N, Ozdogan O, Cakaloglu Y, Idilman R, Karasu Z, Akarca U, et al. Seroprevalence of hepatitis B and C virus infections and risk factors in Turkey: a fieldwork TURHEP study. Clin Microbiol Infect. 2015;21(11):1020-6.
  • 3. Wu T, Li J, Shao L, Xin J, Jiang L, Zhou Q, et al. Development of diagnostic criteria and a prognostic score for hepatitis B virus-related acute-on-chronic liver failure. Gut. 2018;67(12):2181-91.
  • 4. Reddy KR, Beavers KL, Hammond SP, Lim JK, Falck-Ytter YT. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148(1):215-9; quiz e16-7.
  • 5. Fukuda W, Hanyu T, Katayama M, Mizuki S, Okada A, Miyata M, et al. Risk stratification and clinical course of hepatitis B virus reactivation in rheumatoid arthritis patients with resolved infection: final report of a multicenter prospective observational study at Japanese Red Cross Hospital. Arthritis Research & Therapy. 2019;21(1):255.
  • 6. Mahroum N, Watad A, Tiosano S, Hejly A, Mahagna H, Waknin R, et al. Chronic hepatitis B viral infection among RA patients-a cross-sectional control study. Clin Rheumatol. 2019;38(5):1237-41.
  • 7. Etienne S, Vosbeck J, Bernsmeier C, Osthoff M. Prevention of Hepatitis B Reactivation in Patients Receiving Immunosuppressive Therapy: a Case Series and Appraisal of Society Guidelines. J Gen Intern Med. 2023;38(2):490-501.
  • 8. Aygen B, Demir AM, Gümüş M, Karabay O, Kaymakoğlu S, Köksal A, et al. Immunosuppressive therapy and the risk of hepatitis B reactivation: Consensus report. Turk J Gastroenterol. 2018;29(3):259-69.
  • 9. Pattullo V. Prevention of Hepatitis B reactivation in the setting of immunosuppression. Clin Mol Hepatol. 2016;22(2):219-37.
  • 10. Karadağ Ö, Kaşifoğlu T, Özer B, Kaymakoğlu S, Kuş Y, İnanç M, et al. Viral hepatitis screening guideline before biological drug use in rheumatic patients. Eur J Rheumatol. 2016;3(1):25-8.
  • 11. Cabalak M, Bal T, Ocak S. İmmünsüpresif Tedavi Alacak Hastalarda Hepatit Serolojisi. Harran Üniversitesi Tıp Fakültesi Dergisi. 2020;17.
  • 12. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370-98.
  • 13. Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560-99.
  • 14. Lau G, Yu ML, Wong G, Thompson A, Ghazinian H, Hou JL, et al. APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy. Hepatol Int. 2021;15(5):1031-48.
  • 15. Ceylan M, TURKEN M, Singil S, Pelin A, Şükran K. İmmunsupresif Tedavi Alan Hastalarda Hepatit B Reaktivasyonu Riskinin Değerlendirilmesi. İzmir Tıp Fakültesi Dergisi.1(3):112-6.
  • 16. Durak S, Coşar AM. Evaluation of the safety and antiviral efficacy of the tenofovir alafenamide fumarate molecule in immunosuppressed patients. Journal of Health Sciences and Medicine. 2022;5(6):1688-92.
  • 17. Jeong S, Shin HP, Kim HI. Real-World Single-Center Comparison of the Safety and Efficacy of Entecavir, Tenofovir Disoproxil Fumarate, and Tenofovir Alafenamide in Patients with Chronic Hepatitis B. Intervirology. 2022;65(2):94-103.
  • 18. Baranek B, Wang S, Cheung AM, Mishra S, Tan DH. The effect of tenofovir disoproxil fumarate on bone mineral density: a systematic review and meta-analysis. Antivir Ther. 2020;25(1):21-32.
  • 19. Ha NB, Ku K, Ha NB, Chaung KT, Trinh HN, Nguyen MH. Renal Function in Chronic Hepatitis B Patients Treated With Tenofovir Disoproxil Fumarate or Entecavir Monotherapy: A Matched Case-Cohort Study. J Clin Gastroenterol. 2015;49(10):873-7.
  • 20. Su J, Long L, Zou K. Antiviral prophylaxis for preventing reactivation of hepatitis B virus in rheumatic patients: a systematic review and meta-analysis. Clin Rheumatol. 2018;37(12):3201-14.
  • 21. Picardi M, Della Pepa R, Giordano C, Zacheo I, Pugliese N, Mortaruolo C, et al. Tenofovir vs lamivudine for the prevention of hepatitis B virus reactivation in advanced-stage DLBCL. Blood. 2019;133(5):498-501.
  • 22. Yang C, Qin B, Yuan Z, Chen L, Zhou HY. Meta-analysis of prophylactic entecavir or lamivudine against hepatitis B virus reactivation. Ann Hepatol. 2016;15(4):501-11.
  • 23. Chen M-H, Chen M-H, Liu C-Y, Tsai C-Y, Huang D-F, Lin H-Y, et al. Hepatitis B Virus Reactivation in Rheumatoid Arthritis Patients Undergoing Biologics Treatment. The Journal of Infectious Diseases. 2016;215(4):566-73.
  • 24. Padovan M, Filippini M, Tincani A, Lanciano E, Bruschi E, Epis O, et al. Safety of Abatacept in Rheumatoid Arthritis With Serologic Evidence of Past or Present Hepatitis B Virus Infection. Arthritis Care Res (Hoboken). 2016;68(6):738-43.
  • 25. Vassilopoulos D, Delicha EM, Settas L, Andrianakos A, Aslanidis S, Boura P, et al. Safety profile of repeated rituximab cycles in unselected rheumatoid arthritis patients: a long-term, prospective real-life study. Clin Exp Rheumatol. 2016;34(5):893-900.
  • 26. Harigai M, Winthrop K, Takeuchi T, Hsieh TY, Chen YM, Smolen JS, et al. Evaluation of hepatitis B virus in clinical trials of baricitinib in rheumatoid arthritis. RMD Open. 2020;6(1).
  • 27. Lee YH, Bae SC, Song GG. 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(5):527-31.
  • 28. 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.
  • 29. Canzoni M, Marignani M, Sorgi ML, Begini P, Biondo MI, Caporuscio S, et al. Prevalence of Hepatitis B Virus Markers in Patients with Autoimmune Inflammatory Rheumatic Diseases in Italy. Microorganisms. 2020;8(11).
  • 30. Makvandi M, Noormandi Pour S, Teimoori A, Shokri S, Mahmoudvand S, Biparva Haghighi S, et al. Frequency of Hepatitis B Markers in Systemic Lupus Erythematosus Patients in Iran. Asian Pac J Cancer Prev. 2022;23(6):1921-6.
  • 31. Cabalak M, Kimyon G, Bal T. Frequency of Hepatitis B Virus Screening in Patients with Systemic Lupus Erythematosus. Mediterranean Journal of Infection Microbes and Antimicrobials. 2020;9.
  • 32. Yang S, Tian G, Cui Y, Ding C, Deng M, Yu C, et al. Factors influencing immunologic response to hepatitis B vaccine in adults. Sci Rep. 2016;6:27251. 33. Öztürk S, Kaçar M, Toprak S, Çolak O, Öztürk D, Agalar C. Hepatit B Aşılama Verileri; İmmünsüpresif Hastalarda Tek Doz mu? Çift Doz mu? Namık Kemal Tıp Dergisi.8(3):499-506.
Toplam 32 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Bulaşıcı Hastalıklar
Bölüm Orjinal Araştırma
Yazarlar

Ahmet Şahin 0000-0002-8377-8293

Selda Aslan 0000-0001-8695-7118

Yayımlanma Tarihi 30 Eylül 2023
Kabul Tarihi 29 Eylül 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 13 Sayı: 5

Kaynak Göster

AMA Şahin A, Aslan S. Evaluation of HBV Reactivation and Antiviral Prophylaxis in Patients Receiving Immunosuppressive Therapy. J Contemp Med. Eylül 2023;13(5):809-813. doi:10.16899/jcm.1343166