1
Toranomon Hospital Kajigaya, 1-3-1, Kajigaya, Takatsu-ku, Kawasaki-city, Kanagawa, 213-8587, Japan.
2
Toranomon Hospital, 2-2-2, Toranomon, Minato-ku, 105-8470, Japan.
3
Sapporo-Kosei General Hospital, 8-5, Kita 3-jo Higashi, Chuo-ku, Sapporo-city, Hokkaido, 060-0033, Japan.
4
Keiyukai Sapporo Hospital, 1-1, Kita, Hondori 14 chome, Shiroishi-ku, Sapporo-city, Hokkaido, 003-0027, Japan.
5
Nagoya City University Hospital, 1, Aza-Kawasumi, Mizuho, Nagoya, Aichi, 467-8602, Japan.
6
Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
7
Musashino Red Cross Hospital, 1-26-1, Kyonan-cho, Musashino-shi, Tokyo, 180-8610, Japan.
8
National Hospital Organization Nagasaki Medical Center, 2-1001-1, Kubara, Omura-city, Nagasaki, 856-8562, Japan.
9
Obihiro-Kosei General Hospital, 10-1, Nishi 14-jo Minami, Obihiro-city, Hokkaido, 080-0024, Japan.
10
Nippon Medical School Chiba Hokusoh Hospital, 1715, Kamakari, Inzai-City, Chiba, 270-1694, Japan.
11
St. Marianna University School of Medicine Hospital, 2-16-1, Sugao, Miyamae-ku, Kawasaki-city, Kanagawa, 216-8511, Japan.
12
Osaka City University Hospital, 1-5-7, Asahi-machi, Abeno-ku, Osaka-city, Osaka, 545-8586, Japan.
13
Kindai University Hospital, 377-2, Ohnohigashi, Osakasayama-city, Osaka, 589-8511, Japan.
14
Sanin Rosai Hospital, 1-8-1, Kaikeshinden, Yonago-city, Tottori, 683-8605, Japan.
15
National Hospital Organization Kure Medical Center and Chugoku Cancer Center, 3-1, Aoyama-cho, Kure-city, Hiroshima, 737-0023, Japan.
16
Matsuyama Red Cross Hospital, 1, Bunkyo-cho, Matsuyama-city, Ehime, 790-8524, Japan.
17
Ehime Prefectural Central Hospital, 83, Kasugamachi, Matsuyama-city, Ehime, 790-0024, Japan.
18
Kitakyushu City Hospital Organization Kitakyushu Municipal Medical Center, 2-1-1, Bashaku, Kokurakita-ku, Kitakyushu-city, Fukuoka, 802-0077, Japan.
19
Shin-Eikai Hospital, 12-11, Bentencho, Kokurakita-ku, Kitakyushu-city, Fukuoka, 803-0856, Japan.
20
Hamanomachi Hospital, 3-3-1, Nagahama, Chuo-ku, Fukuoka-city, Fukuoka, 810-8539, Japan.
21
Kurume University Hospital, 67, Asahi-machi, Kurume-shi, Fukuoka, 830-0011, Japan.
22
Kumamoto Shinto General Hospital, 3-2-65, Ooe, Chuo-ku, Kumamoto-city, Kumamoto, 862-8655, Japan.
23
GlaxoSmithKline K.K., Akasaka Intercity AIR, 1-8-1, Akasaka, Minato-ku, Tokyo, 107-0052, Japan.
24
GlaxoSmithKline K.K., Akasaka Intercity AIR, 1-8-1, Akasaka, Minato-ku, Tokyo, 107-0052, Japan. [email protected].
25
National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo, 162-8655, Japan.
PMID: 34930140 DOI: 10.1186/s12876-021-02008-9
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/s ... ;draw=2&rank=1.