Tenofovir Alafenamide in the Treatment of Naïve Chronic Hepatitis B: A Single-Centre Retrospective Study

Öz

Chronic hepatitis B (CHB) is a major global health problem affecting approximately 257 million people worldwide. Tenofovir alafenamide (TAF) is a new, effective antiviral drug for chronic hepatitis B. However, real-world data on the efficacy of TAF in treating naive patients are limited. This study aimed to evaluate TAF's efficacy in treating naive CHB patients. Factors associated with virological response and alanine aminotransferase (ALT) normalization were also analyzed in the study. The study included 41 treatment-naive CHB patients who started TAF between January 2021 and December 2022. Demographic, clinical, and laboratory data were collected at baseline and week 48. The primary endpoints were complete virologic response (CVR) and ALT normalization at week 48. At week 48, ALT and hepatitis B virus-deoxyribonucleic acid (HBV DNA) levels decreased to statistically significant levels (both p<0.001). CVR and ALT normalization were achieved in 73% and 76% of patients, respectively. Those who achieved CVR had a higher baseline hepatitis B surface antigen (HBsAg)/HBV DNA ratio than those who achieved partial virologic response (0.79 vs 0.4, p=0.012). ALT normalization was associated with lower baseline ALT and less advanced hepatic necroinflammation and steatosis. TAF provided effective virological suppression and ALT normalization in treatment-naive patients, and the baseline HBsAg/HBV DNA ratio was found to be a parameter predicting virological response. Milder basal necroinflammation and steatosis were significant in favor of ALT normalization, suggesting that TAF is an effective and safe treatment option for patients with CHB.

Anahtar Kelimeler

• Chronic hepatitis B
• tenofovir alafenamide
• treatment-naive
• virological response
• ALT normalization

Naif Kronik Hepatit B Tedavisinde Tenofovir Alafenamid: Tek Merkezli Retrospektif Çalışma

Öz

Kronik hepatit B (KHB), dünya çapında yaklaşık 257 milyon insanı etkileyen önemli bir küresel sağlık sorunudur. Tenofovir alafenamid (TAF), kronik hepatit B tedavisinde kullanılan yeni ve etkili bir antiviral ilaç olmakla birlikte tedaviye naif hastalarda TAF etkinliğine ilişkin gerçek dünya verileri sınırlıdır. Bu çalışmanın amacı, tedaviye naif KHB hastalarında TAF'ın etkinliğini değerlendirmektir. Virolojik yanıt ve alanin aminotransferaz (ALT) normalizasyonu ile ilişkili faktörler de çalışmada analiz edilmiştir. Çalışmaya Ocak 2021-Aralık 2022 tarihleri arasında TAF başlanan 41 tedavi naif KHB hastası dahil edilmiştir. Demografik, klinik ve laboratuvar verileri başlangıçta ve 48. haftada toplanmıştır. Birincil sonlanım noktaları tam virolojik yanıt (TVY) ve 48. haftada ALT normalizasyonu idi. 48. haftada ALT ve hepatit B virüsü-deoksiribonükleik asit (HBV DNA) düzeyleri istatiksel açıdan anlamlı olacak şekilde azalmıştır (her ikisi de p<0.001). Hastaların sırasıyla %73'ünde TVY ve %76'sında ALT normalizasyonu sağlanmıştır. TVY sağlananlarda kısmi virolojik yanıt sağlananlara kıyasla daha yüksek başlangıç hepatit B yüzey antijeni (HBsAg)/HBV DNA oranı vardı (0.79 vs 0.4, p=0.012). ALT normalizasyonunun daha düşük bazal ALT, daha az ilerlemiş hepatik nekroinflamasyon ve steatoz ile ilişkili olduğu görüldü. TAF, tedavi naif hastalarda etkili bir virolojik baskılama ve ALT normalizasyonu sağlamış olup; başlangıç HBsAg/HBV DNA oranı virolojik yanıtı öngören bir parametre olarak tespit edilmiştir. Daha hafif bazal nekroinflamasyon ve steatoz ise ALT normalizasyonu lehine anlamlı bulunmuş, TAF'ın KHB hastaları için etkili ve güvenli bir tedavi seçeneği olduğu düşünülmüştür.

Anahtar Kelimeler

• Kronik hepatit B
• tenofovir alafenamid
• tedaviye naif
• virolojik yanıt
• ALT normalizasyonu

Kaynakça

1. 1. Agarwal K, Fung S, Nguyen T, Cheng W, Sicard É, Ryder S, et al. Twenty-eight day safety, antiviral activity, and pharmacokinetics of tenofovir alafenamide for treatment of chronic hepatitis B infection. J Hepatol. 2015;62(3):533-540. https://doi.org/10.1016/j.jhep.2014.10.035
2. 2. Akhan S, Aynioglu A, Cagatay A, Gonen I, Gunal O, Kaynar T, et al. Management of chronic hepatitis B virus infection: a consensus report of the Study Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases. KLIMIK Derg. 2015;27(S1):2-18. https://doi.org/10.5152/kd.2014.26
3. 3. Alghamdi AS, Alothmani HS, Mogharbel M, Albiladi H, Babatin M. Clinical characteristics of hepatitis B virus patients after switching to tenofovir alafenamide fumarate: a retrospective observational study. Cureus. 2020;12(9):e10380. https://doi.org/10.7759/cureus.10380
4. 4. Buti M, Gane E, Seto WK, Chan HLY, Chuang W-L, Stepanova T, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016;1(3):196-206. https://doi.org/10.1016/S2468-1253(16)30107-8
5. 5. Buti M, Riveiro-Barciela M, Esteban R. Tenofovir Alafenamide Fumarate: A New Tenofovir Prodrug for the Treatment of Chronic Hepatitis B Infection. J Infect Dis. 2017;216:S792-6. https://doi.org/10.1093/infdis/jix135
6. 6. Byrne R, Carey I, Agarwal K. Tenofovir alafenamide in the treatment of chronic hepatitis B virus infection: rationale and clinical trial evidence. Therap Advan Gastroenterol. 2018;11:1756284818786108. https://doi.org/10.1177/1756284818786108
7. 7. Callebaut C, Stepan G, Tian Y, Miller MD. In vitro virology profile of tenofovir alafenamide, a novel oral prodrug of tenofovir with improved antiviral activity compared to that of tenofovir disoproxil fumarate. Antimicrob Agents Chemother. 2015;59(10):5909-16. https://doi.org/10.1128/AAC.01152-15
8. 8. Chan HLY, Buti M, Lim Y-S, Agarwal K, Marcellin P, Brunetto M, et al. Long-term treatment with tenofovir alafenamide for chronic hepatitis B results in high rates of viral suppression and favorable renal and bone safety. Am J Gastroenterol. 2023;10:14309. https://doi.org/10.14309/ajg.0000000000002468

9. 9. Charlton MR, Alam A, Shukla A, Dashtseren B, Lesmana CRA, Duger D, et al. An expert review on the use of tenofovir alafenamide for the treatment of chronic hepatitis B virus infection in Asia. Journal of Gastroenterology. 2020;55(9):811-23. https://doi.org/10.1007/s00535-020-01698-4
10. 10. Chen J, Xu CR, Xi M, Hu WW, Tang ZH, Zang GQ. Predictors of liver histological changes and a sustained virological response to peginterferon among chronic hepatitis B e antigen‐positive patients with normal or minimally elevated alanine aminotransferase levels. J Viral Hepat. 2017;24(7):573-9. https://doi.org/10.1111/jvh.12679
11. 11. Chun HS, Lee JS, Lee HW, Kim BK, Park JY, Kim DY, et al. Prevalence and risk factors of cardiovascular disease in patients with chronic hepatitis B. Dig Dis Sci. 2021;67(7):3412-25. https://doi.org/10.1007/s10620-021-07157-1
12. 12. Hayashi H. Management of thrombocytopenia due to liver cirrhosis: A review. World J Gastroenterol. 2014;20(10):2595. https://doi.org/10.3748/wjg.v20.i10.2595
13. 13. Kaneko S, Kurosaki M, Tamaki N, Itakura J, Hayashi T, Kirino S, et al. Tenofovir alafenamide for hepatitis B virus infection including switching therapy from tenofovir disoproxil fumarate. J Gastroenterol Hepatol. 2019;34(11):200410. https://doi.org/10.1111/jgh.14686
14. 14. Karaman A, Gürsoy Ş, Soyuer I, Karaman H, Torun ME, Yurci MA, et al. Effect of hepatic steatosis on virological response to nucleos(t)ide analogs therapy in patients with chronic hepatitis B. Turk J Med Sci. 2013;43(1):70-4. https://doi.org/10.3906/sag-1202-96
15. 15. Lee HW, Yoo EJ, Kim BK, Kim SU, Park JY, Kim DY, et al. Prediction of development of liver-related events by transient elastography in hepatitis B patients with complete virological response on antiviral therapy. Am J Gastroenterol. 2014;109(8):1241-9. https://doi.org/ 10.1038/ajg.2014.157
16. 16. Li J, Hu C, Chen Y, Zhang R, Fu S, Zhou M, et al. Short-term and long-term safety and efficacy of tenofovir alafenamide, tenofovir disoproxil fumarate and entecavir treatment of acute-on-chronic liver failure associated with hepatitis B. BMC Infect Dis. 2021;21(1):567. https://doi.org/10.1186/s12879-021-06237-x
17. 17. Lim Y, Lampertico P. Editorial: Does TAF have a better or worse safety profile than TDF, to treat hepatitis B? Authors’ reply. Aliment Pharmacol Ther. 2022;55:1044-5. https://doi.org/10.1111/apt.16886
18. 18. Minami T, Tateishi R, Kondo M, Nakagomi R, Fujiwara N, Sato M, et al. Serum alpha-fetoprotein has high specificity for the early detection of hepatocellular carcinoma after hepatitis C virus eradication in patients. Medicine (Baltimore). 2015;94(23):e901. https://doi.org/10.1097/MD.0000000000000901
19. 19. Papatheodoridis GV, Mimidis K, Manolakopoulos S, Gatselis N, Goulis J, Kapatais A, et al. HERACLIS‐TAF: a multi‐centre prospective cohort study on 2‐year safety and efficacy of tenofovir alafenamide in patients with chronic hepatitis B with renal and/or bone disorders or risks. Aliment Pharmacol Ther. 2022;56(4):702-12. https://doi.org/10.1111/apt.17093
20. 20. Peng C-Y, Lai H-C, Su W-P, Lin C-H, Chuang P-H, Chen S-H, et al. Early hepatitis B surface antigen decline predicts treatment response to entecavir in patients with chronic hepatitis B. Sci Rep. 2017;7:42879. https://doi.org/10.1038/srep42879
21. 21. Prati D, Taioli E, Zanella A, Torre ED, Butelli S, Del Vecchio E, et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med. 2002;137(1):1-10. https://doi.org/10.7326/0003-4819-137-1-200207020-00006
22. 22. Qian X, Liu S, Long H, Zhang S, Yan X, Yao M, et al. Reappraisal of the diagnostic value of alpha‐ fetoprotein for surveillance of HBV‐related hepatocellular carcinoma in the era of antiviral therapy. J Viral Hepat. 2020;28(1):20-9. https://doi.org/10.1111/jvh.13388
23. 23. Santantonio TA. Chronic hepatitis B: Advances in treatment. World J Hepat. 2014;6(5):284. https://doi.org/0.4254/wjh.v6.i5.284
24. 24. Sarowar A, Coffin CS, Fung S, Wong A, Doucette K, Truong D, et al. Brief Report: Effect of antiretroviral switch from tenofovir disoproxil fumarate to tenofovir alafenamide on alanine aminotransferase, lipid profiles, and renal function in HIV/HBV-coinfected individuals in a nationwide Canadian study. J Acquir Immune Defic Syndr. 2022;91(4):368-72. https://doi.org/10.1097/QAI.0000000000003079
25. 25. Seto WK, Chang T-T, Chowdhry A, Chen C-Y, Celen MK, Ma X, et al. P1- High viral suppression and improved safety profile of tenofovir alafenamide relative to tenofovir disoproxil fumarate in chronic hepatitis B patients treated for 5 years. Ann Hepat. 2023;28(S1):100905. https://doi.org/10.1016/j.aohep.2023.100905
26. 26. Song JC, Min BY, Kim J-W, Kim JY, Kim YM, Shin CM, et al. Pretreatment serum HBsAg-to-HBV DNA ratio predicts a virologic response to entecavir in chronic hepatitis B. Korean J Hepat. 2011;17(4):268. https://doi.org/10.3350/kjhep.2011.17.4.268
27. 27. Squillace N, Ricci E, Menzaghi B, De Socio GV, Passerini S, Martinelli C, et al. The effect of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on liver enzymes, glucose, and lipid profile. Drug Des Dev Ther. 2020;14:5515-20. https://doi.org/10.2147/DDDT.S274307
28. 28. Suzuki K, Suda G, Yamamoto Y, Abiko S, Kinoshita K, Miyamoto S, et al. Effect of switching from tenofovir disoproxil fumarate to tenofovir alafenamide on lipid profiles in patients with hepatitis B. PLoS One. 2022;17(1):e0261760. https://doi.org/10.1371/journal.pone.0261760
29. 29. van Bömmel F, Berg T. Antiviral therapy of chronic hepatitis B. Intervirology. 2014;57(3-4):171-80. https://doi.org/10.1159/000360945
30. 30. World Health Organization. Hepatitis B factsheet. WHO, https://www.who.int/news‐room/fact‐ sheets/detail/hepatitis‐b (erişim tarihi 14.5.2023)
31. 31. World Health Organization. Global hepatitis report, 2017. WHO, https://www.who.int/publications/i/item/global-hepatitis-report-2017 (erişim tarihi 14.5.2023)