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İmmünsüpresif hastalarda HBV reaktivasyonunun önlenmesi için tenofovir alafenamid profilaksisi: çok merkezli bir çalışma

Year 2022, Volume: 47 Issue: 1, 446 - 454, 31.03.2022

Abstract

Amaç: İmmünsupresif tedavi altındaki yüksek riskli hastalarda hepatit B reaktivasyonu antiviral profilaksi ile önlenebilir. Antiviral seçiminde entekavir (ETC) veya tenofovir disoproksil fumarat (TDF) uzun zamandır kullanılabilmekteyken yakın zamanda kullanıma giren tenofovir alafenamid (TAF) güvenli yan etki profili ile iyi bir alternatif olmuştur. Bu çok merkezli geniş hasta sayılı çalışmada immünsüpresif hasta grubunda tenofovir alafenamidin (TAF) etkinliği ve güvenliği araştırılmıştır.
Gereç ve Yöntem: Altı eğitim ve araştırma hastanesinin 1 Ocak 2019- 30 Eylül 2021 arasındaki kayıtları retrospektif olarak incelenerek immünsüpresif tedavi altında iken hepatit B için antiviral profilaksi başlanan ve en az 6 ay süre ile takip edilen hastalar çalışmaya dahil edilmiştir. Aldıkları immünsüpresif tedavi veya kemoterapiye ayrıca hepatit B serolojilerine göre risk grupları belirlenmiş, hepatit B reaktivasyon varlığı ve yan etkileri yönünden incelenmiştir.
Bulgular: Yaş ortalaması 62.5±29 yıl olan 148 hastanın 85’i (%57.4) TAF, 63’ü (%42.6) tenofovir disoproksil fumarate (TDF) veya entekavir (ETC) ile profilaksi almaktaydı. %83.1’i HBsAg (-) antiHBc (+) %16.9’u HBsAg (+) olarak bulundu; kronik HBV’li hastaların %36 sının HBV DNA’sı saptanabilir düzeyin üzerindeydi. Çoğu (%69.6) hematolojik bir malinite nedeni ile immünsüpresif alırken %89.2’sinin aldığı tedavi yüksek riskli ilaç grubunda idi. Riskler açısından TAF ve diğer tedavileri alanlar arasında farklılık yoktu. Tedavi gruplarının hiçbirinde reaktivasyon ya da yan etkiye rastlanmadı.
Sonuç: Kronik HBV tedavisinde olduğu gibi immünsüpresif tedavi alan bireylerde HBV reaktivasyonunun önlenmesinde de TAF en az TDF ve ETC kadar etkindir. TDF nin böbrek ve kemik yan etkilerinin TAF da görülmemesinin etkin ve güvenli bu tedavi seçeneğini immünsüpresif hastalarda öne çıkaracağını düşünmekteyiz.

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References

  • WHO. Global Hepatitis Report, 2017. Geneva, WHO, 2017.
  • European Centre for Disease Prevention and Control. Hepatitis B. In: ECDC. Annual Epidemiological Report for 2019. Stockholm, ECDC, 2021.
  • 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;21:1020-6.
  • Aygen B, Demir AM, Gümüş M, Karabay O, Kaymakoğlu S, Koksal AS et al. Immunosuppressive therapy and the risk of hepatitis B reactivation: Consensus report. Turk J Gastroenterol. 2018;29:259-69.
  • Loomba R, Jake Liang TJ. Hepatitis B reactivation associated with immune suppressive and biological modifier therapies: current concepts, management strategies and future directions. Gastroenterology. 2017;152:1297–309.
  • Smalls DJ, Kiger RE, Norris LB, Bennett CL, Love BL. Hepatitis B virus reactivation: risk factors and current management strategies. Pharmacotherapy. 2019;39:1190-203.
  • European Association for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol 2017;67:370-98.
  • 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;67:1560-99.
  • Bozkurt I, Ozturk Cerik H, Kir S, Ustaoglu M, Turgut M, Esen S. Evaluation of Hepatitis B screening and reactivation in patients receiving rituximab containing chemotherapy: A single-centre study. Int J Clin Pract. 2021;75:e14685.
  • Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10:1-98.
  • Zhang MY, Zhu GQ, Shi KQ, Zheng JN, Cheng Z, Zou ZL et al. Systematic review with network meta-analysis: Comparative efficacy of oral nucleos(t)ide analogues for the prevention of chemotherapy-induced hepatitis B virus reactivation. Oncotarget. 2016;7:30642–58.
  • Lok A, Bonis P, Hepatitis B virus reactivation associated with immunosuppressive therapy. In UpToDate (Ed R Esteban). Waltham, MA. UpToDate, 2022.
  • Ogawa E, Furusyo N, Nguyen MH. Tenofovir alafenamide in the treatment of chronic hepatitis B: design, development and place in therapy. Drug Des Devel Ther. 2017;11:3197-204.
  • Tenofovir Alafenamide; Highlights of prescribing information. https://www.gilead.com/-/media/files/pdfs/medicines/liver-disease/vemlidy/vemlidy_pi.pdf. (Accessed 02.01.2022):
  • Takakusagi S, Takagi H, Yokoyama Y, Kizawa K, Marubashi K, Kosone T et al. Spontaneous reactivation of hepatitis B virus with a frameshift mutation in the precore region in an elderly hepatitis B virus carrier with lifestyle-related diseases. Clin J Gastroenterol. 2021;14:1202-10.
  • Rashidi-Alavijeh J, Straub K, Achterfeld A, Wedemeyer H, Willuweit K, Herzer K. Safety and efficacy of tenofovir alafenamide in liver transplant recipients: A single center experience. Transpl Infect Dis. 2021;23:e13522.
  • Agarwal K, Brunetto M, Seto WK, Lim YS, Fung S, Marcellin P et al. GS-US-320-0110; GS-US-320-0108 Investigators. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. J Hepatol. 2018;68:672-81.
  • Pisaturo M, Di Caprio G, Calò F, Portunato F, Martini S, Coppola N. Management of HBV reactivation in non-oncological patients. Expert Rev Anti Infect Ther. 2018;16:611-24.
  • Onorato L, Pisaturo M, Camaioni C, Grimaldi P, Codella AV, Calò F et al. Risk and prevention of hepatitis b virus reactivation during immunosuppression for non-oncological diseases. J Clin Med. 2021;10:5201.
  • Hoofnagle JH. Reactivation of hepatitis B. Hepatology 2009;49:156-65.
  • Perrillo RP, Gish R, Falck-Ytter YT. American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148:221-44.
  • Moghoofei M, Mostafaei S, Ashraf-Ganjouei A, Kavosi H, Mahmoudi M. HBV reactivation in rheumatic diseases patients under therapy: A meta-analysis. Microb Pathog. 2018;114:436-43.
  • Choi J, Jo C, Lim YS. Tenofovir versus entecavir on recurrence of hepatitis B virus-related hepatocellular carcinoma after surgical resection. Hepatology. 2021;73:661-73.
  • Türe Z, Kalın Ünüvar G, Kahveci HN, Ulu Kılıç A. Malignite nedenli immünsüpresif alan hastalarda HBV reaktivasyonunun önlenmesi için Tenofovir alafenamid’in etkisi, sözlü sunum. 4. GAEK, Aralık 2020, p.21.

Tenofovir alafenamid prophylaxis for the prevention of HBV reactivation in immunosuppressed subjects: a multicenter study

Year 2022, Volume: 47 Issue: 1, 446 - 454, 31.03.2022

Abstract

Purpose: Reactivation of hepatitis B may be prevented by antiviral therapy in immunosuppressed high risk patients. Entecavir (ETC) and tenofovir disoproksil fumarat (TDF) have been used for a long time and recently introduced tenofovir alafenamid (TAF) seems to be a good alternative with rare side effects. This multicentered study with a large patient population aimed to investigate the effectiveness of tenofovir alafenamid (TAF) in immunsuppressed subjects.
Materials and Methods: The records of six training and research hospitals between January 1, 2019 and September 30, 2021 were retrospectively reviewed, and patients who were started antiviral prophylaxis for hepatitis B and followed up for at least 6 months while under immunosuppressive therapy were included in the study. Risk groups were determined according to the immunosuppressive treatment or chemotherapy they received, as well as hepatitis B serology, and were examined in terms of the presence of hepatitis B reactivation and its side effects.
Results: The mean age of patients was found as 62.5±29. Out of 148 patients, 85 (57.4%) received TAF, 63 (42.6%) received either Entecavir (ETC) or tenofovir disoproksil fumarat (TDF). The majority (83.1%) was found as HBsAg (-) antiHBc (+) and 16.9% was HBsAg (+). HBV DNA was traced in 36% of chronic HBV patients. Most of the patients (69.6%) were receiving immunospuppressives for treatment of a haematologic malignancy and 89.2% was in the high risk treatment group. There was no difference between TAF and the other drugs in terms of risks. Reactivation was not seen in any of the treatment groups.
Conclusion: TAF is as effective as TDF and ETC when used for prophylaxis in immunosuppressed HBV patients. Side effects on kidney and bone are not seen in TAF treatment groups which will probably play a role in preferring this new drug.

References

  • WHO. Global Hepatitis Report, 2017. Geneva, WHO, 2017.
  • European Centre for Disease Prevention and Control. Hepatitis B. In: ECDC. Annual Epidemiological Report for 2019. Stockholm, ECDC, 2021.
  • 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;21:1020-6.
  • Aygen B, Demir AM, Gümüş M, Karabay O, Kaymakoğlu S, Koksal AS et al. Immunosuppressive therapy and the risk of hepatitis B reactivation: Consensus report. Turk J Gastroenterol. 2018;29:259-69.
  • Loomba R, Jake Liang TJ. Hepatitis B reactivation associated with immune suppressive and biological modifier therapies: current concepts, management strategies and future directions. Gastroenterology. 2017;152:1297–309.
  • Smalls DJ, Kiger RE, Norris LB, Bennett CL, Love BL. Hepatitis B virus reactivation: risk factors and current management strategies. Pharmacotherapy. 2019;39:1190-203.
  • European Association for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol 2017;67:370-98.
  • 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;67:1560-99.
  • Bozkurt I, Ozturk Cerik H, Kir S, Ustaoglu M, Turgut M, Esen S. Evaluation of Hepatitis B screening and reactivation in patients receiving rituximab containing chemotherapy: A single-centre study. Int J Clin Pract. 2021;75:e14685.
  • Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10:1-98.
  • Zhang MY, Zhu GQ, Shi KQ, Zheng JN, Cheng Z, Zou ZL et al. Systematic review with network meta-analysis: Comparative efficacy of oral nucleos(t)ide analogues for the prevention of chemotherapy-induced hepatitis B virus reactivation. Oncotarget. 2016;7:30642–58.
  • Lok A, Bonis P, Hepatitis B virus reactivation associated with immunosuppressive therapy. In UpToDate (Ed R Esteban). Waltham, MA. UpToDate, 2022.
  • Ogawa E, Furusyo N, Nguyen MH. Tenofovir alafenamide in the treatment of chronic hepatitis B: design, development and place in therapy. Drug Des Devel Ther. 2017;11:3197-204.
  • Tenofovir Alafenamide; Highlights of prescribing information. https://www.gilead.com/-/media/files/pdfs/medicines/liver-disease/vemlidy/vemlidy_pi.pdf. (Accessed 02.01.2022):
  • Takakusagi S, Takagi H, Yokoyama Y, Kizawa K, Marubashi K, Kosone T et al. Spontaneous reactivation of hepatitis B virus with a frameshift mutation in the precore region in an elderly hepatitis B virus carrier with lifestyle-related diseases. Clin J Gastroenterol. 2021;14:1202-10.
  • Rashidi-Alavijeh J, Straub K, Achterfeld A, Wedemeyer H, Willuweit K, Herzer K. Safety and efficacy of tenofovir alafenamide in liver transplant recipients: A single center experience. Transpl Infect Dis. 2021;23:e13522.
  • Agarwal K, Brunetto M, Seto WK, Lim YS, Fung S, Marcellin P et al. GS-US-320-0110; GS-US-320-0108 Investigators. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. J Hepatol. 2018;68:672-81.
  • Pisaturo M, Di Caprio G, Calò F, Portunato F, Martini S, Coppola N. Management of HBV reactivation in non-oncological patients. Expert Rev Anti Infect Ther. 2018;16:611-24.
  • Onorato L, Pisaturo M, Camaioni C, Grimaldi P, Codella AV, Calò F et al. Risk and prevention of hepatitis b virus reactivation during immunosuppression for non-oncological diseases. J Clin Med. 2021;10:5201.
  • Hoofnagle JH. Reactivation of hepatitis B. Hepatology 2009;49:156-65.
  • Perrillo RP, Gish R, Falck-Ytter YT. American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148:221-44.
  • Moghoofei M, Mostafaei S, Ashraf-Ganjouei A, Kavosi H, Mahmoudi M. HBV reactivation in rheumatic diseases patients under therapy: A meta-analysis. Microb Pathog. 2018;114:436-43.
  • Choi J, Jo C, Lim YS. Tenofovir versus entecavir on recurrence of hepatitis B virus-related hepatocellular carcinoma after surgical resection. Hepatology. 2021;73:661-73.
  • Türe Z, Kalın Ünüvar G, Kahveci HN, Ulu Kılıç A. Malignite nedenli immünsüpresif alan hastalarda HBV reaktivasyonunun önlenmesi için Tenofovir alafenamid’in etkisi, sözlü sunum. 4. GAEK, Aralık 2020, p.21.
There are 24 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research
Authors

Sebnem Senol 0000-0001-7438-7306

Ufuk Sönmez This is me 0000-0001-8578-4892

Tuna Demirdal 0000-0002-9046-5666

Pınar Şen 0000-0003-1365-3329

Deniz Türk This is me 0000-0001-6180-254X

Sabri Atalay 0000-0001-9076-428X

Deniz Akyol 0000-0002-1644-6248

Çiğdem Mermutluoğlu 0000-0003-1836-6281

Mustafa Kemal Çelen 0000-0001-5876-2241

Tansu Yamazhan This is me 0000-0001-5950-0702

Hüsnü Pullukçu 0000-0001-6363-2708

Publication Date March 31, 2022
Acceptance Date February 27, 2022
Published in Issue Year 2022 Volume: 47 Issue: 1

Cite

MLA Senol, Sebnem et al. “İmmünsüpresif Hastalarda HBV Reaktivasyonunun önlenmesi için Tenofovir Alafenamid Profilaksisi: çok Merkezli Bir çalışma”. Cukurova Medical Journal, vol. 47, no. 1, 2022, pp. 446-54.