Kronik Hepatit B Enfeksiyonunda Tenofovir ve Entekavir Tedavi Sonuçlarının Karşılaştırılması

Yıl 2025, Cilt: 22 Sayı: 3, 522 - 530, 29.09.2025

Sezai Tunç , Muhsin Kaya

https://doi.org/10.35440/hutfd.1732641

Öz

Amaç: Bu çalışmada, kronik hepatit B (KHB) enfeksiyonu veya KHB ilişkili kompanse karaciğer sirozu tanısı almış hastalarda, entekavir ve tenofovir tedavilerinin uzun süreli kullanımda virolojik baskılanma, serolojik dönüşüm ve biyokimyasal parametreler üzerindeki etkileri-nin karşılaştırmalı olarak incelenmesi amaçlanmıştır.
Materyal ve Metot: Bu retrospektif kohort çalışmaya, Dicle Üniversitesi Tıp Fakültesi Hastanesi Gastroenteroloji Anabilim Dalı’nda tenofovir veya entekavir tedavisi alan kronik HBV enfeksiyonlu, yalnızca kompanse sirozu olan hastalar da dahil edilmiştir. Karaciğer nakli öyküsü, dekompanse siroz, immünsupresif tedavi, gebelik ve kontrolsüz diyabet dışlama kriterleri olarak belirlenmiştir. Klinik ve labora-tuvar veriler hasta dosyalarından retrospektif olarak toplanmıştır. HBV DNA, ALT ve AST düzeyleri düzenli aralıklarla izlenmiş; serolojik belirteçler (HBsAg, anti-HBs, HBeAg, anti-HBe) ilk yıl üçer aylık aralıklarla ve devamında altı aylık periyotlarla değerlendirilmiştir. Karaciğer biyopsileri, modifiye Knodell (İshak) skorlama sistemi ile analiz edilmiş, hepatik aktivite indeksi ve fibrozis evresi kaydedilmiştir.
Bulgular: Toplam 400 hasta (234 tenofovir, 166 entekavir) çalışmaya dahil edilmiştir. Gruplar, başlangıç özellikleri açısından benzerdi. Virolojik baskılanma oranları genel olarak iki grupta benzer bulunmuştur. Ancak HBeAg pozitif hastalarda 2. yılda entekavir lehine anlamlı bir fark saptanmıştır (p=0.02). HBeAg pozitif hastalar arasında ALT normalleşmesi açısından entekavir tenofovire 6. ayda (p=0.02) ancak 5. yılda ise tenofovir entakavire göre (p=0.04) daha etkili bulunmuştur. HBeAg negatif hastalarda ise 5. yılda ALT normalleşme oranı entekavir grubunda anlamlı olarak daha yüksekti (p=0.007). Biyokimyasal yanıt açısından ise entekavir grubunda 6. Ayda (p=0.016) ve 60. ayda (p=0.045) ALT düzeylerinde daha belirgin normalleşme izlenmiştir. Serolojik yanıt oranları (HBeAg serokonversiyonu ve HBsAg kaybı) iki tedavi grubu arasında farklılık göstermemiştir.
Sonuç: Tenofovir ve entekavir, KHB tedavisinde benzer virolojik ve serolojik etkinlik göstermektedir. Bununla birlikte, entekavir özellik-le bazı hasta alt gruplarında ve tedavinin belirli dönemlerinde biyokimyasal yanıt açısından üstünlük sağlayabilir.

Anahtar Kelimeler

Entekavir , Kronik Hepatit B , Tenofovir

Etik Beyan

2020 yılı öncesi tıpta uzmanlık tezlerinde retrospektif çalışmalarda etik kurul onay şartı olmadığından etik kurul onayı alınmamıştır (Tıpta uzmanlık tezi tarihi 2016 ve tez numarası 440071)

Destekleyen Kurum

Bu çalışma herhangi bir fon tarafından desteklenmemiştir.

Comparison of Tenofovir and Entecavir Treatment Results in Chronic Hepatitis B Infection

Öz

Background: The aim of this study is to comparatively evaluate the long-term effects of entecavir and tenofovir treatments on virologi-cal suppression, serological response, and biochemical parameters in patients diagnosed with chronic hepatitis B (CHB) infection or CHB-related compensated liver cirrhosis.
Materials and Methods: This retrospective cohort study included patients with chronic HBV infection and compensated cirrhosis who received tenofovir or entecavir therapy at the Department of Gastroenterology, Dicle University Faculty of Medicine Hospital. Patients with a history of liver transplantation, decompensated cirrhosis, use of immunosuppressive therapy, pregnancy, or uncontrolled diabetes were excluded from the study. Clinical and laboratory data were retrospectively collected from patient records. HBV DNA, ALT, and AST levels were monitored at regular intervals. Serological markers (HBsAg, anti-HBs, HBeAg, and anti-HBe) were assessed quarterly during the first year and every six months thereafter. Liver biopsy specimens were evaluated using the modified Knodell (Ishak) scoring system, and both the hepatic activity index and fibrosis stage were recorded.
Results: A total of 400 patients were included in the study, with 234 receiving tenofovir and 166 receiving entecavir. The two groups were similar in terms of baseline characteristics. Overall, virological suppression rates were comparable between the groups. However, among HBeAg-positive patients, a significant difference favoring entecavir was observed at the second year of treatment (p=0.02). Regarding ALT normalization in HBeAg-positive patients, entecavir was more effective than tenofovir at month 6 (p=0.02), whereas tenofovir showed greater efficacy at year 5 (p=0.04). In HBeAg-negative patients, the ALT normalization rate at year 5 was significantly higher in the entecavir group (p=0.007). In terms of biochemical response, ALT normalization was more prominent in the entecavir group at both month 6 (p=0.016) and month 60 (p=0.045). Serological response rates, including HBeAg seroconversion and HBsAg loss, did not differ significantly between the two treatment groups.
Conclusion: Tenofovir and entecavir demonstrate comparable virological and serological efficacy in the treatment of chronic HBV infection. However, entecavir may offer superior biochemical response in certain patient subgroups and at specific time points during therapy.

Anahtar Kelimeler

Chronic Hepatitis B , Entecavir , Tenofovir

Kaynakça

• 1. Polaris Observatory Collaborators. Global prevalence, cas-cade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study. Lancet Gastroenterol Hepatol. 2023 Oct;8(10):879-907.
• 2. World Health Organization (WHO). Global hepatitis report 2024: action for access in low- and middle-income count-ries. Geneva: WHO; 2024.
• 3. Dienstag JL. Hepatitis B Virus Enfection. N EngJ Med 2008;359:1486-1500.
• 4. Jeng W.-J., Papatheodoridis G.V., Lok A.S.F. Hepatitis B. Lancet. 2023;401:1039–1052.
• 5. Tozun N, Özdoğan OC, Cakaloglu Y, İdilman R, Karasu Z, Akarca US, et al. A nationwide prevalance study and risk factors for hepatitis A, B, C and D infections in Turkey. He-patology, Volume 52, Supplement S1, 697A, 2010.
• 6. Topçu AW, Söyletir D; Enfeksiyon hastalıkları ve mikrobiyo-lojisi: 3. baskı, İstanbul: Hepatit virusları:2008:147.2:1882-1901.
• 7. Abdelhamed W, El-Kassas M. Hepatitis B virus as a risk fac-tor for hepatocellular carcinoma: there is still much work to do. Liver Res. 2024;8:83e90.
• 8. European Association for the Study of the Liver. Electronic address: easloffice@ easloffice.eu; European Association for the Study of the Liver. EASL Clinical Practice Guidelines on acute-on-chronic liver failure. J Hepatol. 2023;79: 461e491.
• 9. Sarin SK, Kedarisetty CK, Abbas Z, Amarapurkar D, Bihari C, Chan AC, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014. Hepatol Int. 2014 Oct;8(4):453-71.
• 10. Soriano V, Barreiro P, Cachay E, Kottilil S, Fernandez-Montero JV, de Mendoza C. Advances in hepatitis B thera-peutics. Ther Adv Infect Dis. 2020 Oct 15;7:2049936120965027.
• 11. Dusheiko G, Agarwal K, Maini MK. New Approaches to Chronic Hepatitis B. N Engl J Med. 2023 Jan 5;388(1):55-69.
• 12. Fattovich G, Giustina G, Schalm SW, Hadziyannis S, Sanc-hez-Tapias J, Almasio P, et al. Occurrence of hepatocellular carcinoma and decompensation in western European pati-ents with cirrhosis type B. The EUROHEP Study Group on Hepatitis B Virus and Cirrhosis. Hepatology. 1995 Jan;21(1):77-82.
• 13. Chen CJ, Yang HI, Iloeje UH; REVEAL-HBV Study Group. He-patitis B virus DNA levels and outcomes in chronic hepati-tis B. Hepatology. 2009 May;49(5 Suppl):S72-84.
• 14. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, et al; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65-73.
• 15. Yuen MF, Yuan HJ, Wong DK, Yuen JC, Wong WM, Chan AO, et al. Prognostic determinants for chronic hepatitis B in As-ians: therapeutic implications. Gut. 2005 Nov;54(11):1610-4.
• 16. Lai CL, Yuen MF. Chronic hepatitis B- new goals, new tre-atment. N Engl J Med 2008; 359(23): 2488-2491.
• 17. Sriprayoon T, Mahidol C, Ungtrakul T, Chun-On P, So-onklang K, Pongpun W, et al. Efficacy and safety of enteca-vir versus tenofovir treatment in chronic Hepatitis-B pati-ents: A randomized controlled trial. Hepatol Res. 2017;47(3):E161-E168.
• 18. Jeong S, Shin HP, Kim HI. Real-World Single-Center Compa-rison of the Safety and Efficacy of Entecavir, Tenofovir Di-soproxil Fumarate, and Tenofovir Alafenamide in Patients with Chronic Hepatitis-B. Intervirology. 2022;65(2):94-103.
• 19. Ma X, Liu S, Wang M, Wang Y, Du S, Xin Y, et al. Tenofovir Alafenamide Fumarate, Tenofovir Disoproxil Fumarate and Entecavir: Which is the Most Effective Drug for Chronic Hepatitis-B? A Systematic Review and Meta-analysis. J Clin Transl Hepatol. 2021;9(3):335-344.
• 20. Yang S, Ma X, Cai C, Wang H, Xiao F, Yu C. Tenofovir Disop-roxil Fumarate Is Superior to Entecavir in Reducing Hepati-tis-B Surface Antigen for Chronic Hepatitis-B in China: 2-Year Comprehensive Comparative Result of a Matched Comparative Study. Front Med (Lausanne). 2021;8:637126.
• 21. Song W, Bao J. Tenofovir disoproxil fumarate: safe and ef-fective option for managing high-viral-load chronic hepati-tis B. Am J Transl Res. 2025 Apr 15;17(4):3228-3234.
• 22. Cao L, Li L, Yang L, Zhou N, Zhang Y. Efficacy and safety of tenofovir and entecavir in patients with chronic hepatitis B-related cirrhosis: a systematic review and meta-analysis. Front Pharmacol. 2025 Jan 20;16:1507117.
• 23. Woo G, Tomlinson G, Nishikawa Y, Kowgier M, Sherman M, Wong DK, et al. Tenofovir and entecavir are the most ef-fective antiviral agents for chronic hepatitis B: a systematic review and Bayesian meta-analyses. Gastroenterology. 2010 Oct;139(4):1218-29.
• 24. Hsu YC, Jun DW, Peng CY, Yeh ML, Trinh H, Wong GL, et al. Effectiveness of entecavir vs tenofovir disoproxil fumarate for functional cure of chronic hepatitis B in an internatio-nal cohort. Hepatol Int. 2022 Dec;16(6):1297-1307.
• 25. Chen M, Wang H, Zheng Q, Zheng X, Fan J, Ding Y, et al. Comparative efficacy of tenofovir and entecavir in nuc-leos(t)ide analogue-naive chronic hepatitis B: a systematic review and meta-analysis. PLoS One. 2019;14:e0224773.
• 26. Ke W, Liu L, Zhang C, Ye X, Gao Y, Zhou S, et al. Compari-son of efficacy and safety of Tenofovir and Entecavir in chronic hepatitis B virus infection: a systematic review and Meta-analysis. PLoS One. 2014;9:e98865.
• 27. Con D, Goodwin T, Majeed A, Roberts S, Kemp W. Compa-rison of 48-week efficacy of tenofovir vs entecavir for pati-ents with chronic hepatitis B: a network meta-analysis. J Viral Hepat. 2021;28:40–50.