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Sequential HBV treatment with tenofovir alafenamide for patients with chronic hepatitis B: week 96 results from a real-world, multicenter cohort study

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Abstract

Background and aims

Outcome data of sequential hepatitis B virus treatment with tenofovir alafenamide (TAF) are limited. We aimed to assess the effectiveness and renal safety of TAF in chronic hepatitis B (CHB) patients who were previously treated with entecavir (ETV), tenofovir disoproxil fumarate (TDF), or a nucleos(t)ide analogue (NA) combination.

Methods

This multicenter, retrospective, cohort study included 458 consecutive CHB patients who switched to TAF monotherapy after at least 2 years of treatment with another NA. The longitudinal virological/laboratory responses were evaluated up to 96 weeks after switchover. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2.

Results

The proportions of complete viral suppression (CVS) (HBV DNA < 20 IU/mL) at week 96 were 99.0%, 98.5%, and 98.4% in the prior ETV (n = 198), TDF (n = 137), and NA combination (n = 123) groups, respectively. Almost all patients with HBV DNA of 20–2000 IU/mL at baseline achieved CVS at week 96. On multivariable generalized estimated equation analysis, a low quantitative hepatitis surface antigen (qHBsAg) level at baseline was associated with a lower follow-up qHBsAg level (coefficient 0.81, p < 0.001). The eGFR showed greater improvement in patients with CKD compared to those without (coefficient 21.7, p < 0.001). However, the increase of eGFR reached a peak between weeks 24 and 48.

Conclusions

Based on this longitudinal data analysis up to 96 weeks, sequential NA therapy with a switch to TAF is a good option to achieve high viral suppression and renal safety.

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Abbreviations

AASLD:

American Association for the Study of Liver Diseases

ADF:

Adefovir

ALT:

Alanine aminotransferase

BMI:

Body mass index

CHB:

Chronic hepatitis B

CI:

Confidence interval

CKD:

Chronic kidney disease

CVS:

Complete viral suppression

eGFR:

Estimated glomerular filtration rate

ETV:

Entecavir

GEE:

Generalized estimating equation

HBeAg:

Hepatitis B e antigen

HBsAg:

Hepatitis B surface antigen

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HIV:

Human immunodeficiency virus

LAM:

Lamivudine

NA:

Nucleos(t)ide  analogue

qHBsAg:

Quantitative hepatitis B surface antigen

TAF:

Tenofovir alafenamide

TDF:

Tenofovir disoproxil fumarate

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Funding

This study was funded by Gilead Sciences.

Author information

Authors and Affiliations

  1. Department of General Internal Medicine, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan

    Eiichi Ogawa

  2. Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization, Fukuoka, Japan

    Makoto Nakamuta & Naoki Yamashita

  3. Department of Medicine, Fukuoka City Hospital, Fukuoka, Japan

    Toshimasa Koyanagi

  4. Department of Hepatology, Steel Memorial Yawata Hospital, Kitakyushu, Japan

    Aritsune Ooho

  5. General Internal Medicine, Taihaku Avenue Clinic, Fukuoka, Japan

    Norihiro Furusyo

  6. Kajiwara Clinic, Kitakyushu, Japan

    Eiji Kajiwara

  7. Department of Internal Medicine, Chihaya Hospital, Fukuoka, Japan

    Kazufumi Dohmen

  8. Department of Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan

    Akira Kawano

  9. Center for Liver Disease, Kokura Medical Center, National Hospital Organization, Kitakyushu, Japan

    Takeaki Satoh

  10. Department of Medicine, Hamanomachi Hospital, Fukuoka, Japan

    Kazuhiro Takahashi

  11. Department of Medicine, Kyushu Central Hospital, Fukuoka, Japan

    Koichi Azuma

  12. The Center for Liver Disease, Shin-Kokura Hospital, Kitakyushu, Japan

    Nobuyuki Yamashita

  13. Department of Gastroenterology, Kyushu Cancer Center, Fukuoka, Japan

    Rie Sugimoto

  14. Amagase Clinic, Kitakyushu, Japan

    Hiromasa Amagase

  15. Department of Gastroenterology, Kyushu Rosai Hospital, Kitakyushu, Japan

    Masami Kuniyoshi

  16. Department of Internal Medicine, JCHO Kyushu Hospital, Kitakyushu, Japan

    Yasunori Ichiki

  17. Department of Internal Medicine, Kyushu Railway Memorial Hospital, Kitakyushu, Japan

    Chie Morita

  18. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Masaki Kato

  19. Graduate School of Nutritional Sciences, Nakamura Gakuen University, Fukuoka, Japan

    Masaki Kato

  20. Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Shinji Shimoda

  21. Department of Internal Medicine, Haradoi Hospital, Fukuoka, Japan

    Hideyuki Nomura

  22. Kyushu General Internal Medicine Center, Haradoi Hospital, Fukuoka, Japan

    Jun Hayashi

Authors
  1. Eiichi Ogawa
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  2. Makoto Nakamuta
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  22. Jun Hayashi
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Consortia

The Kyushu University Liver Disease Study (KULDS) Group

Contributions

All authors were involved in the design of the study, acquisition of samples and/or analysis. EO drafted the manuscript. All authors contributed to the critical discussion of the results and approved the final version of the article.

Corresponding author

Correspondence to Eiichi Ogawa.

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Conflict of interest

Eiichi Ogawa has received speaker fees from Gilead Sciences and AbbVie. Makoto Nakamuta, Toshimasa Koyanagi, Aritsune Ooho, Norihiro Furusyo, Eiji Kajiwara, Kazufumi Dohmen, Akira Kawano, Takeaki Satoh, Kazuhiro Takahashi, Koichi Azuma, Nobuyuki Yamashita, Naoki Yamashita, Rie Sugimoto, Hiromasa Amagase, Masami Kuniyoshi, Yasunori Ichiki, Chie Morita, Masaki Kato, Shinji Shimoda, Hideyuki Nomura, and Jun Hayashi declare that they have no conflicts of interest.

Ethical approval

The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and the STROBE statement. It was approved by the Ethics Committees of Kyushu University Hospital and each study site and is registered as a clinical study on the University Hospital Medical Information Network (ID 000034696).

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Ogawa, E., Nakamuta, M., Koyanagi, T. et al. Sequential HBV treatment with tenofovir alafenamide for patients with chronic hepatitis B: week 96 results from a real-world, multicenter cohort study. Hepatol Int 16, 282–293 (2022). https://doi.org/10.1007/s12072-021-10295-3

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