Bursa Uludağ Üniversitesi Sağlık Uygulama ve Araştırma Merkezi'nde immünsüpresif tedavi nedenli hepatit B reaktivasyon riski olan hastalarda profilaktik tenofovir alafenamid kullanımının retrospektif incelenmesi
Retrospective investigation of prophylactic tenofovir alafenamide USE in patients at risk of hepatitis B reactivation DUE to immunosuppressive therapy in Bursa Uludag University HEALTH practice and research center
Yazar: SERAY TÜRE AYDIN
Danışman: PROF. DR. SELİM GÜREL
Bursa Uludağ Üniversitesi / Tıp Fakültesi / İç Hastalıkları Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2022
Konu: Gastroenteroloji = Gastroenterology
Dizin: Bursa = Bursa ; Hepatit B = Hepatitis B ; Hepatit B virüsü = Hepatitis B virus ; Profilaksi = Prophylaxis ; Tenofovir = Tenofovir ; Tenofovir alafenamid fumarat = Tenofovir alafenamide fumarate ; İmmünosüpresyon = Immunosuppression

Özet:
Hepatit B virüsü  (HBV) ile enfekte olmuş bireyler immünsüpresif veya antikanser tedavileri aldıklarında HBV reaktivasyonu (HBVr) riski artmaktadır.  HBV reaktivasyonu ciddi morbidite ve mortalite ile sonuçlanabilmektedir. Günümüzde kanser tedavileri, monoklonal antikor tedavisi, steroid kullanımı, biyolojik ajanlarla tedavi olan hastaların sayısı giderek artmaktadır. İmmünsüpresif tedavi öncesi hepatit taraması yapılmalı, hepatit B reaktivasyon riskine göre proflaktik antiviral tedavi başlanmalıdır. 
Çalışmamızda Ocak 2019-Mart 2022 tarihleri arasında immünsüpresif tedavi nedenli proflaktif tenofovir alafenamid fumarat (TAF) kullanan 211 hastanın retrospektif incelenmesi yapılmıştır. Hastaların demografik özellikleri, tedavi öncesi ve sonrası hepatit serolojisi ve laboratuvar özellikleri, altta yatan hastalıkları, immünsüpresif tedavileri, serolojik riskleri, HBV reaktivasyon risk durumları değerlendirildi. 
 Tanı anında 26 (%12,3) hasta HBsAg pozitif olup, 185 (%87,7) hasta ise HBsAg negatif/ anti-HBc total pozitifliği vardır. Anti-CD20 monoklonal antikorları HBV reaktivasyonu için yüksek riskli immünsüpresif ajan olup,  %23,70 hastanın tedavisinde kullanılmıştır.  Tedavi öncesi ve sonrası değerler karşılaştırılığında HBsAg, anti-HBc total, anti-HBs serolojisinde ve labarotuvar özelliklerinde anlamlı farklılık tespit edilmemiştir. HBV DNA ise tedavi sonrasında anlamlı olarak azalmıştır. 
Sonuç olarak; retrospektif olarak analizi yapılan 211 hastada reaktivasyon gözlenmemiştir. Bu çalışmada TAF'ın da HBVr önlemede diğer antiviraller kadar etkin olduğu gösterilmiştir. Renal fonksiyon bozukluğu olanlarda renal doz ayarı gerektirmemesi ve renal fonksiyonlar üzerine olumsuz etkisi olmaması, HBV DNA'yı baskılaması, yan etki profilinin az olması gibi sebeplerle güvenle proflaksi tedavisinde de kullanılabilir.
Anahtar kelimeler: HBV, reaktivasyon, immünosüpresyon, tenofovir alafenamid fumarat.

Abstract:
The risk of HBV reactivation( HBVr) increases when HBV-infected individuals receive immunosuppressive or anticancer treatments. HBV reactivation can cause serious morbidity and mortality. The number of patients receiving antineoplastic agents, monoclonal antibodies, steroids, and biological agents is increasing. Hepatitis screening should be performed prior to immunosuppressive therapy, and prophylactic antiviral therapy should be initiated according to the risk of hepatitis B reactivation.
Our study included 211 patients on immunosuppressive treatment and receiving prophylactic tenofovir alafenamide fumarate (TAF) between January 2019 and March 2022. Patients' demographic characteristics, hepatitis serology and laboratory results before and after treatment, underlying disease, immunosuppressive treatments,  serological risks, and HBV reactivation risk status were evaluated.
At the time of diagnosis, 26 (12.3%) patients tested positive for HBsAg, whereas 185 (87.7%) patients were HBsAg negative and anti-HBc total positive 23.70% of patients received anti-CD20 monoclonal antibodies, which are immunosuppressive agents with a significant risk of HBV reactivation. No statistically significant difference was found between pre-and post-treatment values in HBsAg, anti-HBc total, anti-HBs serology, or laboratory results. HBV DNA decreased significantly after treatment.
No reactivation was observed in the retrospective analysis of 211 patients. In this study, TAF was shown to be as effective as other antivirals in preventing HBVr. TAF supresses HBV DNA, has a minimal side-effect profile, and may be used safely in prophylactic therapy in patients with renal impairment since it does not require renal dosage adjustment and has no detrimental effect on renal functions.
Keywords: HBV, reactivation, immunosuppression, tenofovir alafenamide fumarate.

The risk of HBV reactivation( HBVr) increases when HBV-infected individuals receive immunosuppressive or anticancer treatments. HBV reactivation can cause serious morbidity and mortality. The number of patients receiving antineoplastic agents, monoclonal antibodies, steroids, and biological agents is increasing. Hepatitis screening should be performed prior to immunosuppressive therapy, and prophylactic antiviral therapy should be initiated according to the risk of hepatitis B reactivation.
Our study included 211 patients on immunosuppressive treatment and receiving prophylactic tenofovir alafenamide fumarate (TAF) between January 2019 and March 2022. Patients' demographic characteristics, hepatitis serology and laboratory results before and after treatment, underlying disease, immunosuppressive treatments,  serological risks, and HBV reactivation risk status were evaluated.
At the time of diagnosis, 26 (12.3%) patients tested positive for HBsAg, whereas 185 (87.7%) patients were HBsAg negative and anti-HBc total positive 23.70% of patients received anti-CD20 monoclonal antibodies, which are immunosuppressive agents with a significant risk of HBV reactivation. No statistically significant difference was found between pre-and post-treatment values in HBsAg, anti-HBc total, anti-HBs serology, or laboratory results. HBV DNA decreased significantly after treatment.
No reactivation was observed in the retrospective analysis of 211 patients. In this study, TAF was shown to be as effective as other antivirals in preventing HBVr. TAF supresses HBV DNA, has a minimal side-effect profile, and may be used safely in prophylactic therapy in patients with renal impairment since it does not require renal dosage adjustment and has no detrimental effect on renal functions.
Keywords: HBV, reactivation, immunosuppression, tenofovir alafenamide fumarate.