Impact of tumor necrosis factor alpha antagonist treatment on antibody titer of hepatitis B surface antigen

Abstract

Aim: Tumor necrosis factor alpha antagonists (anti-TNF-α) have recently been used successfully in various diseases. On the other hand, due to their potential immunogenic effects, they cause hepatitis B virus (HBV) reactivation. The objective of this study is to examine the change in the levels of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) in patients with negative HBsAg who were administered different anti-TNF-α drugs as well as the factors that influence this change. Methods: This research was designed as a retrospective cohort study. Patients with autoimmune diseases who were followed up at General Internal Medicine outpatient clinics between 2012 and 2019, screened for hepatitis B virus (HBV) infection prior to treatment, checked for serological markers (HBsAg, anti-HBs, hepatitis B core antigen antibody (anti-HBc)), and treated with anti-TNF for at least a year were included. The inclusion criteria were as follows: Patients with negative HBsAg and whose liver function tests were within normal limits, and the exclusion criteria included patients with positive HBsAg and whose liver function tests were above the normal upper limit. Results: A total of 221 adult patients who were treated with anti-TNF-α were included in the study. The pretreatment anti-HBs levels of the patients were significantly higher than the posttreatment levels (P<0.001). Of the 211 patients with positive pretreatment anti-HBs levels, 17 patients had posttreatment anti-HBs levels below 10 IU/L. The anti-HBs levels of five patients with positive anti-HBc dropped below 10 IU/L. Conclusions: The anti-HBs levels of the patients who were administered anti-TNF-α agent decreased significantly, whereas there was no reactivation of HBV or de novo HBV infection in HBsAg-negative patients. It was observed in a small group of patients (8.0%) that the levels of anti-HBs decreased to a risky level.

Keywords

• Tumor necrosis factor antagonist
• Hepatitis B surface antigen antibody
• Autoimmune diseases

Tümör nekroz faktörü alfa antagonisti tedavisinin hepatit B yüzey antijeninin antikor düzeyine etkisi

Öz

Amaç: Tümör nekroz faktör alfa antagonisleri (anti-TNF-α) bir çok hastalıkta başarıyla kullanılmaktadır. Öte yandan, potansiyel immünojenik etkileri nedeniyle, hepatit B virüsü (HBV) yeniden aktivasyonuna neden olurlar. Bu çalışmanın amacı, farklı anti-TNF- α ilaçları ile uygulanan hepatit B yüzey antijeni (HBsAg) negatif hastalarda, HBsAg antikoru (anti-HBs) düzeylerindeki değişimi ve etkileyen faktörleri incelemektir. Yöntemler: Bu araştırma, retrospektif kohort çalışma olarak tasarlanmıştır. Otoimmün hastalıkları nedeniyle 2012-2019 yılları arasında Genel Dahiliye polikliniğine başvuran ve anti-TNF-α tedavi ile tedavi edilen ve en az 1 yıl bu tedaviyi alan ve Hepatit B virusu için tarama amaçlı serolojik belirteçleri (HBsAg, anti-HBs, hepatit B kor antijen antikoru (anti-HBc)) değerlendirilen hastalar çalışmaya alındı. Dahil edilme kriterleri; HBsAg negatif olan ve karaciğer fonksiyon testleri normal sınırlar içinde olan hastalar ve dışlama kriterleri ise; HBsAg pozitif ve karaciğer fonksiyon testleri yüksek olan hastalar. Bulgular: Anti-TNF-α ile tedavi edilen toplam 221 erişkin hasta çalışmaya dahil edildi. Hastaların tedavi öncesi anti-HBs düzeyleri, tedavi sonrası düzeyler ile karşılaştırıldığında, anlamlı derecede yüksekti (P<0,001). Tedavi öncesi anti-HBs düzeyleri pozitif (titre ve aşılı veya virusla karşılaşmış) 211 hastanın 17'sinde tedavi sonrası anti-HBs düzeyleri 10 IU / L'nin altındaydı. Anti-HBc pozitif beş hastanın anti-HBs seviyeleri 10 IU / L'nin altına düştü. Sonuç: Anti-TNF-α tedavi uygulanan hastalarda anti-HBs düzeyleri önemli ölçüde azalırken, HBsAg-negatif hastalarda HBV veya de novo HBV enfeksiyonu için reaktivasyon yoktu. Küçük bir grup hastada (%8,0) anti-HBs düzeylerinin riskli bir seviyeye düştüğü gözlendi.

Anahtar Kelimeler

• Tümör nekroz faktör antagonisti
• Hepatit B yüzey antijeni antikoru
• Otoimmun hastalık

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