BMC Gastroenterology (Dec 2021)

Switching from entecavir to tenofovir disoproxil fumarate for HBeAg-positive chronic hepatitis B patients: a phase 4, prospective study

  • Fumitaka Suzuki,
  • Yoshiyuki Suzuki,
  • Yoshiyasu Karino,
  • Yasuhito Tanaka,
  • Masayuki Kurosaki,
  • Hiroshi Yatsuhashi,
  • Tomofumi Atarashi,
  • Masanori Atsukawa,
  • Tsunamasa Watanabe,
  • Masaru Enomoto,
  • Masatoshi Kudo,
  • Naoto Maeda,
  • Hiroshi Kohno,
  • Kouji Joko,
  • Kojiro Michitaka,
  • Koichiro Miki,
  • Kazuhiro Takahashi,
  • Tatsuya Ide,
  • Shigetoshi Fujiyama,
  • Tomoko Kohno,
  • Hiroshi Itoh,
  • Sakiyo Tsukamoto,
  • Yuko Suzuki,
  • Yoshiaki Kawano,
  • Wataru Sugiura,
  • Hiromitsu Kumada

DOI
https://doi.org/10.1186/s12876-021-02008-9
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 10

Abstract

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Abstract Background Tenofovir disoproxil fumarate (TDF) is widely used and recommended as first-line treatment for patients infected with the hepatitis B virus (HBV). However, current data are limited regarding the efficacy and safety of switching to TDF for the treatment of chronic hepatitis B in hepatitis B e-antigen (HBeAg)-positive patients who are virologically suppressed with another nucleos(t)ide analogue. The primary objective of this study was to evaluate the hepatitis B surface antigen (HBsAg) reduction potential of switching from entecavir (ETV) to TDF at week 48 in HBeAg-positive chronic hepatitis B patients with undetectable serum HBV-DNA. Methods In this multicenter, single-arm, open-label, phase 4 clinical study, 75 participants currently treated with ETV 0.5 mg once daily were switched to TDF 300 mg once daily for 96 weeks. Results At week 48, 3/74 participants (4%) achieved 0.25 log10 reduction of HBsAg levels from baseline (the primary endpoint). Mean HBsAg reduction was −0.14 log10 IU/mL and 12% (9/74) achieved 0.25 log10 reduction by 96 weeks. No participants achieved HBsAg seroclearance. HBsAg reduction at weeks 48 and 96 was numerically greater in participants with higher alanine aminotransferase levels (≥ 60 U/L). Seventeen participants (25%) achieved HBeAg seroclearance up to week 96. No participants experienced viral breakthrough. All drug-related adverse events (18 participants [24%]) were mild in intensity, including an increase in urine beta-2-microglobulin (15 participants [20%]). Conclusions In conclusion, HBsAg reduction was limited after switching from ETV to TDF in this study population. Further investigation is warranted to better understand the clinical impact of switching from ETV to TDF. ClinicalTrials.gov: NCT03258710 registered August 21, 2017. https://clinicaltrials.gov/ct2/show/NCT03258710?term=NCT03258710&draw=2&rank=1

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