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Retreatment Efficacy and Renal Safety of Tenofovir Alafenamide, Entecavir, and Tenofovir Disoproxil Fumarate After Entecavir or Tenofovir Cessation

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Abstract

Background

We aimed to compare the one-year retreatment efficacy and renal safety of entecavir, tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) after HBV relapse in patients who discontinued entecavir or TDF.

Methods

This retrospective study included 289 chronic hepatitis B (CHB) patients without cirrhosis who received entecavir (n = 93), TDF (n = 103), or TAF (n = 86) retreatment for at least 12 months after entecavir or TDF cessation.

Results

The rate of virological response (HBV DNA < 20 IU/mL) at 12 months of retreatment was 79/93 (84.9%) in the entecavir group, 92/103 (89.3%) in the TDF group, and 72/86 (83.7%) in the TAF group. The rate of ALT normalization (ALT ≤ 40 U/L) after 12 months of retreatment was 76/93 (81.7%) in the entecavir group, 77/103 (74.7%) in the TDF group , and 73/86 (84.9%) in the TAF group. There was no significant difference in the rates of virological response (p = 0.495) and ALT normalization (p = 0.198) among the three groups. Multivariate analysis showed that lower HBV DNA and HBsAg levels at baseline were independently associated with virological response at 12 months of retreatment. The TDF group (37.8 ± 34.8 U/L) had higher ALT levels at 12 months of retreatment than the TAF (27. ± 17.9 U/L, p = 0.015) and entecavir (28.3 ± 19.3 U/L, p = 0.022) groups. In patients with eGFR 60–90 mL/min/1.73 m2, eGFR change between baseline and 12 months of retreatment increased in the entecavir and TAF groups and decreased in the TDF group.

Conclusions

TAF could be one of the retreatment options for retreatment of HBV relapse after entecavir or TDF cessation.

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Abbreviations

ALT:

Alanine aminotransferase

eGFR:

Estimated Glomerular filtration rate

HBV:

Hepatitis B virus

HBeAg:

Hepatitis B e antigen

HBsAg:

Hepatitis B surface antigen

CHB:

Chronic hepatitis B

NA:

Nucleoside analogues

HCC:

Hepatocellular carcinoma

TAF:

Tenofovir alafenamide

TDF:

Tenofovir disoproxil fumarate

References

  1. Liaw YF, Chu CM. Hepatitis B virus infection. Lancet 2009;373:582–592.

    Article  CAS  Google Scholar 

  2. Lok AS, McMahon BJ, Brown RS Jr et al. Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta-analysis. Hepatology 2016;63:284–306.

    Article  CAS  Google Scholar 

  3. Ono A, Suzuki F, Kawamura Y et al. Long-term continuous entecavir therapy in nucleos(t)ide-naive chronic hepatitis B patients. J Hepatol. 2012;57:508–514.

    Article  CAS  Google Scholar 

  4. Chen CH, Hung CH, Hu TH et al. Association between level of hepatitis B surface antigen and relapse after entecavir therapy for chronic hepatitis B virus infection. Clin Gastroenterol Hepatol. 2015;13:1984–1992.

    Article  CAS  Google Scholar 

  5. Ma TL, Hu TH, Hung CH et al. Incidence and predictors of retreatment in chronic hepatitis B patients after discontinuation of entecavir or tenofovir treatment. PLoS One. 2019;14:e0222221.

    Article  CAS  Google Scholar 

  6. Babusis D, Phan TK, Lee WA et al. Mechanism for effective lymphoid cell and tissue loading following oral administration of nucleotide prodrug GS-7340. Mol Pharm. 2013;10:459–466.

    Article  CAS  Google Scholar 

  7. Agarwal K, Brunetto M, Seto WK et al. 96 Weeks treatment of tenofovir alafenamide vs tenofovir disoproxil fumarate for hepatitis B virus infection. J Hepatol. 2018;68:672–681.

    Article  CAS  Google Scholar 

  8. Buti M, Gane E, Seto WK 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;1:196–206.

    Article  Google Scholar 

  9. Chan HLY, Fung S, Seto WK et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. The Lancet Gastroenterology & Hepatology. 2016;1:185–195.

    Article  Google Scholar 

  10. Liaw YF, Kao JH, Piratvisuth T et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int. 2012;6:531–561.

    Article  Google Scholar 

  11. Lee CM, Chen CH, Lu SN et al. Prevalence and Clinical Implications of Hepatitis B Virus Genotypes in Southern Taiwan. Scandinavian J Gastroenterol. 2003;38:95–101.

    Article  CAS  Google Scholar 

  12. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120:c179-184.

    Article  Google Scholar 

  13. Wu IT, Hu TH, Hung CH et al. Comparison of the efficacy and safety of entecavir and tenofovir in nucleos(t)ide analogue-naive chronic hepatitis B patients with high viraemia: a retrospective cohort study. Clin Microbiol Infect. 2017;23:464–469.

    Article  CAS  Google Scholar 

  14. Han Y, Zeng A, Liao H et al. The efficacy and safety comparison between tenofovir and entecavir in treatment of chronic hepatitis B and HBV related cirrhosis: A systematic review and Meta-analysis. Int Immunopharmacol. 2017;42:168–175.

    Article  CAS  Google Scholar 

  15. Chen CH, Hsu YC, Lu SN et al. The incidence and predictors of HBV relapse after cessation of tenofovir therapy in chronic hepatitis B patients. J Viral Hepat. 2018;25:590–597.

    Article  CAS  Google Scholar 

  16. Kuo MT, Hu TH, Hung CH et al. Hepatitis B virus relapse rates in chronic hepatitis B patients who discontinue either entecavir or tenofovir. Aliment Pharmacol Ther. 2019;49:218–228.

    Article  CAS  Google Scholar 

  17. Wang JC, He LL, Chen Q. Comparison of re-treatment outcomes of lamivudine plus adefovir or entecavir in chronic hepatitis B patients with viral relapse after cessation of adefovir. Eur Rev Med Pharmacol Sci. 2013;17:1162–1168.

    CAS  Google Scholar 

  18. Hung CH, Hu TH, Lu SN et al. Tenofovir versus entecavir in treatment of chronic hepatitis B virus with severe acute exacerbation. Antimicrob Agents Chemother. 2015;59:3168–3173.

    Article  CAS  Google Scholar 

  19. Hou J, Ning Q, Duan Z et al. 3-year treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for chronic HBV infection in China. J Clin Transl Hepatol. 2021;9:324–334.

    Google Scholar 

  20. Jeng WJ, Chen YC, Liaw YF. Great and rapid HBsAg decline in patients with on-treatment hepatitis flare in early phase of potent antiviral therapy. J Viral Hepat. 2018;25:421–428.

    Article  CAS  Google Scholar 

  21. Kumada T, Toyoda H, Tada T et al. Comparison of the impact of tenofovir alafenamide and entecavir on declines of hepatitis B surface antigen levels. Eur J Gastroenterol Hepatol. 2021;32:255–260.

    Article  Google Scholar 

  22. Itokawa N, Atsukawa M, Tsubota A et al. Sequential therapy from entecavir to tenofovir alafenamide versus continuous entecavir monotherapy for patients with chronic hepatitis B. JGH Open. 2021;5:34–40.

    Article  Google Scholar 

  23. Kaneko S, Kurosaki M, Tamaki N et al. Tenofovir alafenamide for hepatitis B virus infection including switching therapy from tenofovir disoproxil fumarate. J Gastroenterol Hepatol. 2019;34:2004–2010.

    Article  CAS  Google Scholar 

  24. Wursthorn K, Jung M, Riva A et al. Kinetics of hepatitis B surface antigen decline during 3 years of telbivudine treatment in hepatitis B e antigen-positive patients. Hepatology. 2010;52:1611–1620.

    Article  CAS  Google Scholar 

  25. Marcellin P, Buti M, Krastev Z et al. Kinetics of hepatitis B surface antigen loss in patients with HBeAg-positive chronic hepatitis B treated with tenofovir disoproxil fumarate. J Hepatol. 2014;6:1228–1237.

    Article  Google Scholar 

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Acknowledgments

This study was supported by grants NMRPG8G6102 from the Ministry of Science and Technology and CMRPG8F0221 from the Chang Gung Memorial Hospital, Taiwan.

Funding

Ministry of Science and Technology, Taiwan, NMRPG8G6102, Chien-Hung Chen, Chang Gung Memorial Hospital, CMRPG8F0221, Chien-Hung Chen.

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Authors and Affiliations

  1. Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan

    Shao-Ming Chiu, Kuo-Chin Chang, Tsung-Hui Hu, Chao-Hung Hung, Jing-Houng Wang, Sheng-Nan Lu & Chien-Hung Chen

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  1. Shao-Ming Chiu
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  2. Kuo-Chin Chang
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Correspondence to Chien-Hung Chen.

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Chiu, SM., Chang, KC., Hu, TH. et al. Retreatment Efficacy and Renal Safety of Tenofovir Alafenamide, Entecavir, and Tenofovir Disoproxil Fumarate After Entecavir or Tenofovir Cessation. Dig Dis Sci 68, 665–675 (2023). https://doi.org/10.1007/s10620-022-07657-8

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