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Safety and Effectiveness of Tenofovir Alafenamide in Usual Clinical Practice Confirms Results of Clinical Trials: TARGET-HBV

Digestive Diseases and Sciences volume 67, pages 2637–2645 (2022)Cite this article

Abstract

Background

Nucleos(t)ide analogues, with a proven record of safety and efficacy, have been the therapy of choice for over a decade for the treatment of chronic hepatitis B. The approval of tenofovir alafenamide (TAF) in 2016 provided an additional treatment option.

Aims

The aim of this study was to evaluate the characteristics and clinical outcomes of patients treated with TAF in usual clinical practice.

Methods

Retrospective data from electronic health records was obtained from those enrolled in TARGET-HBV, a longitudinal observational cohort study of patients with chronic hepatitis B managed according to local practice standards at community and academic medical centers throughout the U.S.

Results

Of 500 patients enrolled, most were male (66%) and of Asian race (66%) with median age of 55 years. Cirrhosis was evident in 15%. Most patients (82%) had switched to TAF after treatment with other antivirals. The perceived safety profile of TAF was cited as the primary reason for changing therapy (32%). TAF was well tolerated and only 4 patients discontinued therapy due to adverse event during a median duration of TAF dosing of 74 weeks. Among those with paired laboratory data 12–18 months after switching to TAF, biochemical response and HBV DNA suppression was maintained. Most patients had normal renal function which was essentially unchanged throughout follow-up.

Conclusions

TAF is frequently utilized in routine clinical practice due to the perception of its improved safety profile. The current study supports the growing body of evidence regarding the safety and effectiveness of TAF.

Trial Registration ClinicalTrials.gov identifier: NCT03692897, https://clinicaltrials.gov/ct2/show/NCT03692897.

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Fig. 1

Abbreviations

TDF:

Tenofovir disoproxil fumarate

HBV:

Hepatitis B virus

HBeAg:

Hepatitis B e-antigen

TAF:

Tenofovir alafenamide

ALT:

Alanine aminotransferase

DEXA:

Dual-energy X-ray absorptiometry

HCV:

Hepatitis C virus

CrCl:

Creatinine clearance

References

  1. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261–283.

    Article  Google Scholar 

  2. European Association for the Study of the Liver. Electronic address EEE, European Association for the Study of the L. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370–398.

    Article  Google Scholar 

  3. 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.

    CAS  Article  Google Scholar 

  4. Nguyen MH, Yang HI, Le A, Henry L, Nguyen N, Lee MH, et al. Reduced incidence of hepatocellular carcinoma in cirrhotic and noncirrhotic patients with chronic hepatitis B treated with tenofovir-A propensity score-matched study. J Infect Dis. 2019;219:10–18.

    CAS  Article  Google Scholar 

  5. Kim SU, Seo YS, Lee HA, Kim MN, Lee YR, Lee HW, et al. A multicenter study of entecavir versus tenofovir on prognosis of treatment-naive chronic hepatitis B in South Korea. J Hepatol. 2019;71:456–464.

    CAS  Article  Google Scholar 

  6. Papatheodoridis GV, Idilman R, Dalekos GN, Buti M, Chi H, van Boemmel F, et al. The risk of hepatocellular carcinoma decreases after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B. Hepatology. 2017;66:1444–1453.

    CAS  Article  Google Scholar 

  7. Kim WR, Loomba R, Berg T, Aguilar Schall RE, Yee LJ, Dinh PV, et al. Impact of long-term tenofovir disoproxil fumarate on incidence of hepatocellular carcinoma in patients with chronic hepatitis B. Cancer. 2015;121:3631–3638.

    CAS  Article  Google Scholar 

  8. Liu K, Choi J, Le A, Yip TC, Wong VW, Chan SL, et al. Tenofovir disoproxil fumarate reduces hepatocellular carcinoma, decompensation and death in chronic hepatitis B patients with cirrhosis. Aliment Pharmacol Ther. 2019;50:1037–1048.

    CAS  Article  Google Scholar 

  9. Singal AK, Fontana RJ. Meta-analysis: oral antiviral agents in adults with decompensated hepatitis B virus cirrhosis. Aliment Pharmacol Ther. 2012;35:674–689.

    CAS  Article  Google Scholar 

  10. Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381:468–475.

    CAS  Article  Google Scholar 

  11. Young K, Liu B, Bhuket T, Younossi Z, Saab S, Ahmed A, et al. Long-term trends in chronic hepatitis B virus infection associated liver transplantation outcomes in the United States. J Viral Hepat. 2017;24:789–796.

    CAS  Article  Google Scholar 

  12. Buti M, Tsai N, Petersen J, Flisiak R, Gurel S, Krastev Z, et al. Seven-year efficacy and safety of treatment with tenofovir disoproxil fumarate for chronic hepatitis B virus infection. Dig Dis Sci. 2015;60:1457–1464. https://doi.org/10.1007/s10620-014-3486-7.

    CAS  Article  PubMed  Google Scholar 

  13. Marcellin P, Wong DK, Sievert W, Buggisch P, Petersen J, Flisiak R, et al. Ten-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B virus infection. Liver Int. 2019;39:1868–1875.

    CAS  Article  Google Scholar 

  14. Marcellin P, Heathcote EJ, Buti M, Gane E, de Man RA, Krastev Z, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med. 2008;359:2442–2455.

    CAS  Article  Google Scholar 

  15. Min IS, Lee CH, Shin IS, Lee NE, Son HS, Kim SB, et al. Treatment outcome and renal safety of 3-year tenofovir disoproxil fumarate therapy in chronic hepatitis B patients with preserved glomerular filtration rate. Gut Liver. 2019;13:93–103.

    CAS  Article  Google Scholar 

  16. Wong GL, Chan HL, Tse YK, Yip TC, Lam KL, Lui GC, et al. Chronic kidney disease progression in patients with chronic hepatitis B on tenofovir, entecavir, or no treatment. Aliment Pharmacol Ther. 2018;48:984–992.

    CAS  Article  Google Scholar 

  17. Fong TL, Lee BT, Tien A, Chang M, Lim C, Ahn A, et al. Improvement of bone mineral density and markers of proximal renal tubular function in chronic hepatitis B patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide. J Viral Hepat. 2019;26:561–567.

    CAS  Article  Google Scholar 

  18. Seto WK, Asahina Y, Brown TT, Peng CY, Stanciu C, Abdurakhmanov D, et al. Improved bone safety of tenofovir alafenamide compared to tenofovir disoproxil fumarate over 2 years in patients with chronic HBV infection. Clin Gastroenterol Hepatol. 2018. https://doi.org/10.1016/j.cgh.2018.06.023.

    Article  PubMed  Google Scholar 

  19. Sajith KG, Kapoor N, Shetty S, Goel A, Zachariah U, Eapen CE, et al. Bone health and impact of tenofovir treatment in men with hepatitis-B related chronic liver disease. J Clin Exp Hepatol. 2018;8:23–27.

    Article  Google Scholar 

  20. Ogawa E, Furusyo N, Nguyen MH. Tenofovir alafenamide in the treatment of chronic hepatitis B: design, development, and place in therapy. Drug Des Dev Ther. 2017;11:3197–3204.

    CAS  Article  Google Scholar 

  21. Chan HL, Fung S, Seto WK, Chuang WL, Chen CY, Kim HJ, 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. Lancet Gastroenterol Hepatol. 2016;1:185–195.

    Article  Google Scholar 

  22. Buti M, Gane E, Seto WK, Chan HL, Chuang WL, 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;1:196–206.

    Article  Google Scholar 

  23. Terrault NA, Zeuzem S, Di Bisceglie AM, Lim JK, Pockros PJ, Frazier LM, et al. Effectiveness of Ledipasvir–Sofosbuvir combination in patients with hepatitis C virus infection and factors associated with sustained virologic response. Gastroenterology. 2016;151:1131–1140.e5.

    CAS  Article  Google Scholar 

  24. Lampertico P, Buti M, Fung S, Ahn SH, Chuang WL, Tak WY, et al. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patients with chronic hepatitis B: a randomised, double-blind, phase 3, multicentre non-inferiority study. Lancet Gastroenterol Hepatol. 2020;5:441–453.

    Article  Google Scholar 

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Authors and Affiliations

  1. Sandra Atlas Bass Center for Liver Diseases, Zucker School of Medicine at Hofstra/Northwell, 400 Community Drive, Manhasset, NY, 11030, USA

    David E. Bernstein

  2. San Jose Gastroenterology, 2331 Montpelier Dr., Suite B, San Jose, CA, 95116, USA

    Huy N. Trinh

  3. University of Miami School of Medicine, 1500 N.W. 12 Ave., E-1101, Miami, FL, 33136, USA

    Eugene R. Schiff

  4. Georgetown University Hospital, 3800 Reservoir Rd NW, 2PHC, Washington, DC, 20007, USA

    Coleman I. Smith

  5. Target RWE, 2520 Meridian Pkwy, Suite 105, Durham, NC, 27713, USA

    Andrea R. Mospan, Richard C. Zink & Michael W. Fried

  6. Division of Gastroenterology and Hepatology, University of Michigan, 1500 East Medical Center Drive, 3912 Taubman Center, SPC 5362, Ann Arbor, MI, 48109, USA

    Anna S. Lok

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  1. David E. Bernstein
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  2. Huy N. Trinh
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Corresponding author

Correspondence to Anna S. Lok.

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Conflict of interest

DEB: Receives grants from Gilead, Pfizer, Protagonist, Assembly Biosciences, Durect, Mallinckrodt, Novartis, Mirum, Pliant, Boehringer Ingelheim, Abbvie and serves as a consultant to Gilead, Abbvie. HNT: grants from Gilead, Assembly Biosciences, Intercept; speaker: Gilead, Abbvie; consultant: Gilead; stocks: Gilead. ERS: Grant support: Eiger, Galmed, Zydus, Celgene, Beckman, Biokit, Bristol Myers Squibb, Conatus, Celgene, Discovery Life Sciences, Genfit, Gilead, Intercept, Novartis, Novo Nordisk, Orasure Technologies, Ortho Diagnostics, Pfizer, Prometheus Lab, Roche Diagnostics, Shire, Siemens, Target RWE, Tobira, Glaxo Smith Kline; Royalties: Wiley. CIS: No relevant conflicts of interest. ARM, RCZ: Employee of Target RWE. MWF: Chief Medical Officer for Target RWE and receives personal fees and is a stockholder in the company. He reports grants paid to the University of North Carolina from Gilead, Abbvie, National Institutes of Health and Merck, outside the submitted work. ASL: Receives research grants from Bristol-Myers Squibb, Gilead and TARGET RWE (paid to University of Michigan), and serves as consultant/advisor for Ambys, Bristol-Myers Squibb, Huahui, Lilly, and TARGET RWE. Target RWE is the sponsor of the TARGET-HBV study and is solely responsible for data collection and analysis and the decision to publish, as well as preparation of the manuscript with co-authors. TARGET-HBV is a collaboration among academic and community investigators and the pharmaceutical industry and is supported in part by funding from Gilead.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Bernstein, D.E., Trinh, H.N., Schiff, E.R. et al. Safety and Effectiveness of Tenofovir Alafenamide in Usual Clinical Practice Confirms Results of Clinical Trials: TARGET-HBV. Dig Dis Sci 67, 2637–2645 (2022). https://doi.org/10.1007/s10620-021-07033-y

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Keywords

  • Hepatitis B
  • Tenofovir disoproxil fumarate (TDF)
  • Antiviral therapy
  • HBV DNA