Kinetics of the hepatitis B core-related antigen and treatment responses in chronic hepatitis B patients treated with tenofovir alafenamide

Norio Itokawa; Masanori Atsukawa; Akihito Tsubota; Toru Ishikawa; Hidenori Toyoda; Koichi Takaguchi; Tsunamasa Watanabe; Chikara Ogawa; Atsushi Hiraoka; Hironao Okubo; Haruki Uojima; Makoto Chuma; Akito Nozaki; Keizo Kato; Shigeru Mikami; Joji Tani; Asahiro Morishita; Toshifumi Tada; Toru Asano; Tomonori Senoh; Tsunekazu Oikawa; Tomomi Okubo; Takashi Kumada; Katsuhiko Iwakiri

doi:10.1111/hepr.14052

Kinetics of the hepatitis B core-related antigen and treatment responses in chronic hepatitis B patients treated with tenofovir alafenamide

Hepatol Res. 2024 Apr 29. doi: 10.1111/hepr.14052. Online ahead of print.

Authors

Norio Itokawa¹, Masanori Atsukawa¹, Akihito Tsubota², Toru Ishikawa³, Hidenori Toyoda⁴, Koichi Takaguchi⁵, Tsunamasa Watanabe⁶, Chikara Ogawa⁷, Atsushi Hiraoka⁸, Hironao Okubo⁹, Haruki Uojima¹⁰, Makoto Chuma¹¹, Akito Nozaki¹¹, Keizo Kato¹², Shigeru Mikami¹³, Joji Tani¹⁴, Asahiro Morishita¹⁴, Toshifumi Tada¹⁵, Toru Asano¹⁶, Tomonori Senoh⁵, Tsunekazu Oikawa¹⁷, Tomomi Okubo¹⁸, Takashi Kumada¹⁹, Katsuhiko Iwakiri¹

Affiliations

¹ Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan.
² Project Research Units (PRU) Research Center for Medical Science The Jikei University School of Medicine, Tokyo, Japan.
³ Department of Hepatology, Saiseikai Niigata Hospital, Niigata, Japan.
⁴ Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan.
⁵ Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
⁶ Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
⁷ Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan.
⁸ Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
⁹ Department of Gastroenterology, Juntendo University Nerima Hospital, Tokyo, Japan.
¹⁰ Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
¹¹ Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan.
¹² Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan.
¹³ Department of Internal Medicine, Division of Gastroenterology, Kikkoman General Hospital, Noda, Japan.
¹⁴ Department of Gastroenterology, Kagawa University Graduate School of Medicine, Kagawa, Japan.
¹⁵ Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Hyogo, Japan.
¹⁶ Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.
¹⁷ Department of Gastroenterology and Hepatology, The Jikei University School of Medicine, Tokyo, Japan.
¹⁸ Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan.
¹⁹ Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan.

PMID: 38685853
DOI: 10.1111/hepr.14052

Abstract

Aim: An association between hepatitis B core-related antigen (HBcrAg) kinetics and hepatocarcinogenesis during nucleoside (t)id analog (NA) treatment has recently been reported. HBcrAg kinetics and factors associated with HBcrAg response during tenofovir alafenamide (TAF) administration remain unclear. In this multicenter retrospective study, we aimed to clarify the efficacy and safety of TAF in treatment-naïve patients with chronic hepatitis B, focusing on the reduction in HBcrAg levels.

Methods: Patients were treated with TAF monotherapy for 96 weeks, and the kinetics of HBcrAg during treatment and the factors associated with HBcrAg response (defined as a change in HBcrAg of -1 log IU/mL from baseline) were evaluated.

Results: The study population comprised 241 patients, 36.9% of whom were HBeAg-positive. The median baseline HBcrAg level was 4.7 log IU/mL. The median change in HBcrAg from baseline was -1.1 log IU/mL at 96 weeks after treatment. The HBcrAg response rate at 96 weeks was 56.6% (43/76). Multivariate analysis revealed high alanine transaminase level as an independent baseline factor associated with HBcrAg response at 96 weeks of treatment (p = 4.53 × 10^-6). No correlation was found between the HBcrAg and hepatitis B surface antigen kinetics in patients treated with TAF monotherapy.

Conclusions: In TAF monotherapy for patients with chronic hepatitis B, HBcrAg levels were significantly decreased and baseline alanine transaminase level is an important factor associated with HBcrAg reduction. As no correlation was found between HBcrAg and reduced hepatitis B surface antigen levels in this study, HBcrAg kinetics in addition to hepatitis B surface antigen may need to be monitored during TAF treatment.

Keywords: hepatitis B core‐related antigen; hepatitis B surface antigen; tenofovir alafenamide.