Risk of Hepatitis B Virus Reactivation in Patients with Neurological Diseases Receiving Anti-CD20 Therapies
Öz
ABSTRACT
Objective: Anti-CD20 therapies, including ocrelizumab, rituximab, and ofatumumab, are widely used in treating immune-mediated neurological diseases. However, these therapies may increase the risk of hepatitis B virus (HBV) reactivation, particularly in patients with prior HBV exposure. Despite the recognized preventive measures for managing HBV reactivation, specific data regarding the safety of anti-CD20 therapies in this context remain limited.
This retrospective study aims to evaluate the risk of HBV reactivation among patients with neurological disorders treated with anti-CD20 therapies in a single-center cohort from Türkiye.
Methods: We reviewed the records of 580 patients who received at least one dose of anti-CD20 therapies between July 2018 and March 2024. HBV serological markers were assessed at baseline and during follow-up. Patients were stratified based on HBV serostatus, and antiviral prophylaxis rates were documented. Serological follow-up data were reviewed for seroconversion.
Results: Of the patients, 12.24% showed anti-HBc positivity, with higher rates in the ocrelizumab group (15.57%) compared to rituximab (8.08%) and none in the ofatumumab group. Among the anti-HBs positive group, the prophylaxis rate was 78%, while it was 100% in the anti-HBs negative side. No seroconversion cases were observed, regardless of prophylaxis status.
Conclusions: Our findings indicate that anti-CD20 therapies do not pose a detectable risk of HBV reactivation in patients with immune-mediated neurological disorders, even when antiviral prophylaxis is not given to those who are anti-HBs positive. However, further prospective studies with larger cohorts must confirm these results and improve HBV management in this patient population.
Anahtar Kelimeler
Anti-CD20 Therapies HBV Reactivation Multiple Sclerosis Ocrelizumab Antiviral Prophylaxis
Kaynakça
- 1. Aygen B, Demir AM, Gümüş M, et al. Immunosuppressive therapy and the risk of hepatitis B reactivation: Consensus report. Turkish J Gastroenterol Off J Turkish Soc Gastroenterol. 2018;29(3):259-269. doi:10.5152/tjg.2018.18263
- 2. 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):215-217. doi:10.1053/j.gastro.2014.10.039
- 3. Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560-1599. doi:10.1002/hep.29800
- 4. Lau G, Yu M-L, Wong G, et al. APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy. Hepatol Int. 2021;15(5):1031-1048. doi:10.1007/s12072-021-10239-x
- 5. Tozun N, Ozdogan O, Cakaloglu Y, et al. Seroprevalence of hepatitis B and C virus infections and risk factors in Turkey: a fieldwork TURHEP study. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2015;21(11):1020-1026. doi:10.1016/j.cmi.2015.06.028
- 6. Holtkamp C, Fiedler M, Dittmer U, Anastasiou OE. The Course of Anti-HBc Antibodies over Time in Immunocompromised Hosts. Vaccines. 2022;10(2). doi:10.3390/vaccines10020137
- 7. Pei S-N, Ma M-C, Wang M-C, et al. Analysis of hepatitis B surface antibody titers in B cell lymphoma patients after rituximab therapy. Ann Hematol. 2012;91(7):1007-1012. doi:10.1007/s00277-012-1405-6
- 8. Hung M-H, Tien Y-C, Chiu Y-M. Risk factors for losing hepatitis B virus surface antibody in patients with HBV surface antigen negative/surface antibody positive serostatus receiving biologic disease-modifying anti-rheumatic drugs: a nested case-control study. Adv Rheumatol (London, England). 2021;61(1):22. doi:10.1186/s42358-021-00173-9
- 9. Cho Y, Yu SJ, Cho EJ, et al. High titers of anti-HBs prevent rituximab-related viral reactivation in resolved hepatitis B patient with non-Hodgkin’s lymphoma. J Med Virol. 2016;88(6):1010-1017. doi:10.1002/jmv.24423
- 10. Marzo B, Vidal-Jordana A, Castilló J, et al. Hepatitis B reactivation is a rare event among patients with resolved infection undergoing anti-CD20 antibodies in monotherapy without antiviral prophylaxis: results from the HEBEM study. J Neurol. 2024;271(1):134-140. doi:10.1007/s00415-023-11973-y
- 11. Buonomo AR, Viceconte G, Calabrese M, et al. Management of hepatitis B virus prophylaxis in patients treated with disease-modifying therapies for multiple sclerosis: a multicentric Italian retrospective study. J Neurol. 2022;269(6):3301-3307. doi:10.1007/s00415-022-11009-x
- 12. Çelik M, Baba C, Irmak Ç, Özakbaş S, Avkan-Oğuz V. Risk of hepatitis B virus reactivation in people with multiple sclerosis treated with ocrelizumab: an observational study from Turkey. J Neurol. 2024;271(7):4131-4137. doi:10.1007/s00415-024-12333-0
Nörolojik Hastalığı Bulunan ve Anti-CD20 Tedavisi Alan Hastalarda Hepatit B Virüsü Reaktivasyon Riski
Öz
ÖZ
Amaç: Ocrelizumab, rituksimab ve ofatumumab gibi anti-CD20 tedavileri, immun aracılı nörolojik hastalıkların tedavisinde yaygın olarak kullanılmaktadır. Ancak, bu tedaviler, özellikle daha önce hepatit B virüsü (HBV) ile karşılaşmış hastalarda HBV reaktivasyonu riskini artırabilir. HBV reaktivasyonunun yönetimi için tanımlanan önleyici tedbirlere rağmen, bu bağlamda anti-CD20 tedavilerinin güvenliği hakkında spesifik veriler sınırlıdır. Bu retrospektif çalışma, Türkiye’deki tek merkezli bir kohortta anti-CD20 tedavisi alan ve nörolojik hastalığı bulunan hastalarda HBV reaktivasyonu riskini değerlendirmeyi amaçlamaktadır.
Yöntemler: Temmuz 2018 ile Mart 2024 arasında en az bir doz anti-CD20 tedavisi almış 580 hastanın kayıtları incelenmiştir. HBV serolojik belirteçleri başlangıçta ve takip sırasında değerlendirilmiştir. Hastalar, HBV serostatusuna göre kategorize edilmiş ve antiviral profilaksi oranları kaydedilmiştir. Serolojik takip verileri, serokonversiyon için gözden geçirilmiştir.
Bulgular: Hastaların %12,24’ü anti-HBc pozitifti; ocrelizumab grubunda %15,57; rituksimab grubunda ise %8,08 oranında pozitiflik gözlemlendi, ofatumumab grubunda ise anti-HBc pozitif hasta bulunmamaktaydı. Anti-HBs pozitif olan grupta profilaksi oranı %78, anti-HBs negatif olan grupta ise %100’dü. Profilaksi durumuna bakılmaksızın serokonversiyon vakası gözlemlenmedi.
Sonuçlar: Bulgularımız, anti-CD20 tedavilerinin, özellikle anti-HBs pozitif olan hastalarda antiviral profilaksi uygulanmıyor olsa dahi, immun aracılı nörolojik hastalıkları bulunan hastalarda HBV reaktivasyonu riskini tespit edilebilir şekilde arttırmadığını göstermektedir. Ancak, bu sonuçların doğrulanması ve HBV yönetiminin iyileştirilmesi için daha geniş kohortlarla yapılacak prospektif çalışmalara ihtiyaç vardır.
Anahtar Kelimeler
Anti-CD20 tedavileri HBV reaktivasyonu Multiple Skleroz Okrelizumab Antiviral Profilaksi
Kaynakça
- 1. Aygen B, Demir AM, Gümüş M, et al. Immunosuppressive therapy and the risk of hepatitis B reactivation: Consensus report. Turkish J Gastroenterol Off J Turkish Soc Gastroenterol. 2018;29(3):259-269. doi:10.5152/tjg.2018.18263
- 2. 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):215-217. doi:10.1053/j.gastro.2014.10.039
- 3. Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560-1599. doi:10.1002/hep.29800
- 4. Lau G, Yu M-L, Wong G, et al. APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy. Hepatol Int. 2021;15(5):1031-1048. doi:10.1007/s12072-021-10239-x
- 5. Tozun N, Ozdogan O, Cakaloglu Y, et al. Seroprevalence of hepatitis B and C virus infections and risk factors in Turkey: a fieldwork TURHEP study. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2015;21(11):1020-1026. doi:10.1016/j.cmi.2015.06.028
- 6. Holtkamp C, Fiedler M, Dittmer U, Anastasiou OE. The Course of Anti-HBc Antibodies over Time in Immunocompromised Hosts. Vaccines. 2022;10(2). doi:10.3390/vaccines10020137
- 7. Pei S-N, Ma M-C, Wang M-C, et al. Analysis of hepatitis B surface antibody titers in B cell lymphoma patients after rituximab therapy. Ann Hematol. 2012;91(7):1007-1012. doi:10.1007/s00277-012-1405-6
- 8. Hung M-H, Tien Y-C, Chiu Y-M. Risk factors for losing hepatitis B virus surface antibody in patients with HBV surface antigen negative/surface antibody positive serostatus receiving biologic disease-modifying anti-rheumatic drugs: a nested case-control study. Adv Rheumatol (London, England). 2021;61(1):22. doi:10.1186/s42358-021-00173-9
- 9. Cho Y, Yu SJ, Cho EJ, et al. High titers of anti-HBs prevent rituximab-related viral reactivation in resolved hepatitis B patient with non-Hodgkin’s lymphoma. J Med Virol. 2016;88(6):1010-1017. doi:10.1002/jmv.24423
- 10. Marzo B, Vidal-Jordana A, Castilló J, et al. Hepatitis B reactivation is a rare event among patients with resolved infection undergoing anti-CD20 antibodies in monotherapy without antiviral prophylaxis: results from the HEBEM study. J Neurol. 2024;271(1):134-140. doi:10.1007/s00415-023-11973-y
- 11. Buonomo AR, Viceconte G, Calabrese M, et al. Management of hepatitis B virus prophylaxis in patients treated with disease-modifying therapies for multiple sclerosis: a multicentric Italian retrospective study. J Neurol. 2022;269(6):3301-3307. doi:10.1007/s00415-022-11009-x
- 12. Çelik M, Baba C, Irmak Ç, Özakbaş S, Avkan-Oğuz V. Risk of hepatitis B virus reactivation in people with multiple sclerosis treated with ocrelizumab: an observational study from Turkey. J Neurol. 2024;271(7):4131-4137. doi:10.1007/s00415-024-12333-0
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Sinirbilim (Diğer) |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 30 Haziran 2025 |
| Gönderilme Tarihi | 16 Kasım 2024 |
| Kabul Tarihi | 27 Haziran 2025 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 8 Sayı: 2 |
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