Hagiwara Satoru, Nishida Naoshi, Ida Hiroshi, Ueshima Kazuomi, Minami Yasunori, Takita Masahiro, Aoki Tomoko, Morita Masahiro, Chishina Hirokazu, Komeda Yoriaki, Yoshida Akihiro, Hayashi Hidetoshi, Nakagawa Kazuhiko, Kudo Masatoshi
Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan.
Hepatol Res. 2022 Sep;52(9):754-761. doi: 10.1111/hepr.13798. Epub 2022 Jun 15.
The risk of hepatitis B virus (HBV) reactivation with immune checkpoint inhibitors (ICIs) is an important issue that has not yet been fully investigated. ICI is also expected to have an antiviral effect on HBV due to its immune tolerance inhibitory effect. We herein investigated the risk of HBV reactivation and the antiviral effect of ICI administration.
This study included 892 patients on ICIs between September 2014 and May 2021 at our hospital. The frequency of HBV reactivation and antiviral effects were investigated.
Among the 892 patients who underwent ICI, 27 were hepatitis B surface antigen (HBsAg) positive. HBV reactivation was evaluated in 24 cases, among which 4.1% (1/24) had HBV reactivation. Nucleic acid analog prophylaxis was not administered to patients with reactivation. In a study of 15 cases, the amount of HBsAg decreased from baseline; 2.18 ± 0.77 log to 48 weeks later; 1.61 ± 1.38 log (p = 0.17). Forty-eight weeks after the start of ICI, disappearance of HBsAg was observed in two out of 15 cases (13.3%), and one case each with and without nucleic acid analog.
In rare cases, HBsAg-positive patients may be reactivated by ICI administration. On the other hand, when ICI is administered, it is expected to have an antiviral effect on HBV due to its immune tolerance inhibitory effect, and future drug development is expected.
免疫检查点抑制剂（ICI）引发乙型肝炎病毒（HBV）再激活的风险是一个尚未得到充分研究的重要问题。由于ICI具有免疫耐受抑制作用，其对HBV也有望产生抗病毒作用。我们在此研究了HBV再激活的风险以及ICI给药的抗病毒效果。
本研究纳入了2014年9月至2021年5月在我院接受ICI治疗的892例患者。对HBV再激活的频率和抗病毒效果进行了研究。
在接受ICI治疗的892例患者中，27例乙型肝炎表面抗原（HBsAg）呈阳性。对24例患者进行了HBV再激活评估，其中4.1%（1/24）出现了HBV再激活。再激活患者未接受核酸类似物预防治疗。在一项针对15例患者的研究中，HBsAg量从基线水平下降；48周后从2.18±0.77 log降至1.61±1.38 log（p = 0.17）。ICI开始治疗48周后，15例患者中有2例（13.3%）出现HBsAg消失，其中1例使用了核酸类似物，1例未使用。
在罕见情况下，HBsAg阳性患者可能因ICI给药而发生再激活。另一方面，ICI给药时，由于其免疫耐受抑制作用，有望对HBV产生抗病毒作用，未来有望开发相关药物。
