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Effectiveness of tenofovir alafenamide for chronic hepatitis B patients with a poor response to the previously used nucleos(t)ide analogs

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

Few studies have demonstrated the potency of tenofovir alafenamide (TAF) in patients with poor response to other nucleos(t)ide analogs (NAs).

Methods

We conducted a retrospective study comprising consecutive 40 patients exhibiting a poor response to other NAs, who subsequently received TAF-containing regimens. The primary outcome was the prevalence of virological response (VR) at each time and maintained virological response (MVR) under TAF-containing regimens until week 96.

Results

In the entire cohort, the prevalence of MVR was 71.1% (27/38). Further, poor tenofovir disoproxil fumarate (TDF) response was significantly associated with a lower prevalence of MVR (p = 0.014). In TDF-naïve patients, the prevalence of MVR was 92.3% (12/13) and 62.5% (5/8) in patients with lamivudine resistance (LAM-r) and entecavir resistance (ETV-r), respectively. Further, viral load and HBeAg status at baseline were associated with a lower prevalence of MVR (p = 0.013). Among the seven patients with prior TDF exposure, 2 patients achieved MVR. Among them, one patient with development of viral breakthrough during TDF/LAM achieved MVR after switching to TAF/ETV. In contrast, one of the five patients with non-MVR had three substitutions (rtS106C, rtD134N/S, and rtL269I) of quadruple mutations in addition to ETV-r. Other patients with rtA181T + rtN236T also could not achieve MVR.

Conclusion

TAF exhibited high antiviral potency in patients with LAM-r and ETV-r. However, TAF potency was associated with previous TDF response, viral load, and HBeAg status at baseline. Additionally, a quadruple mutation may impact tenofovir resistance; however, further studies are needed to verify this.

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Acknowledgements

Hiromitsu Kumada has served as a speaker for Gilead Sciences, AbbVie Inc., MSD K.K., Eisai Co., Ltd, and Dainippon Sumitomo Pharma. Masahiro Kobayashi served as a speaker for Eisai Co., Ltd. Norio Akuta served as a speaker for the Gilead Sciences, AbbVie Inc. This study was supported in part by the Program for Basic and Clinical Research on Hepatitis, Japan Agency for Medical Research and Development (AMED) (Grant number: JP21fk0210084), Okinaka Memorial Institute for Medical Research, and Taiju Life Social Welfare Foundation.

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Authors and Affiliations

  1. Department of Hepatology, Toranomon Hospital, 2-2-2, Toranomon, Minato-ku, Tokyo, 105-8470, Japan

    Daiki Yamashige, Tetsuya Hosaka, Fumitaka Suzuki, Shunichiro Fujiyama, Yusuke Kawamura, Hitomi Sezaki, Norio Akuta, Masahiro Kobayashi, Yoshiyuki Suzuki, Satoshi Saitoh, Yasuji Arase, Kenji Ikeda & Hiromitsu Kumada

  2. Research Institute for Hepatology, Toranomon Hospital, Kawasaki, Japan

    Mariko Kobayashi

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  1. Daiki Yamashige
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Contributions

DY: Study concept and design, data collection, data analysis and interpretation, and drafting of the manuscript. TH: Study concept and design, data collection, data analysis and interpretation, and critical review of the manuscript. FS: Data collection, data analysis and interpretation, and review of the manuscript. SF: Data collection and review of the manuscript. YK: Data collection and review of the manuscript. HS: Data collection and review of the manuscript. NA: Data collection and review of the manuscript. MK: Data collection and review of the manuscript. YS: Data collection and review of the manuscript. SS: Data collection and review of the manuscript. YA: Data collection and review of the manuscript. KI: Data collection and review of the manuscript. MK: Assistance with data collection, sequencing drug resistances, and review of the manuscript. HK: Study concept and design, data collection, data analysis and interpretation, and critical review of the manuscript. All authors had access to the data and participated in the writing of this manuscript.

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Correspondence to Tetsuya Hosaka.

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Yamashige, D., Hosaka, T., Suzuki, F. et al. Effectiveness of tenofovir alafenamide for chronic hepatitis B patients with a poor response to the previously used nucleos(t)ide analogs. J Gastroenterol 56, 1008–1021 (2021). https://doi.org/10.1007/s00535-021-01826-8

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  • DOI: https://doi.org/10.1007/s00535-021-01826-8

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