TY - JOUR
T1 - Ultra-high sensitivity HBsAg assay can diagnose HBV reactivation following rituximab-based therapy in patients with lymphoma
AU - Kusumoto, Shigeru
AU - Tanaka, Yasuhito
AU - Suzuki, Ritsuro
AU - Watanabe, Takashi
AU - Nakata, Masanobu
AU - Sakai, Rika
AU - Fukushima, Noriyasu
AU - Fukushima, Takuya
AU - Moriuchi, Yukiyoshi
AU - Itoh, Kuniaki
AU - Nosaka, Kisato
AU - Choi, Ilseung
AU - Sawa, Masashi
AU - Okamoto, Rumiko
AU - Tsujimura, Hideki
AU - Uchida, Toshiki
AU - Suzuki, Sachiko
AU - Okamoto, Masataka
AU - Takahashi, Tsutomu
AU - Sugiura, Isamu
AU - Onishi, Yasushi
AU - Kohri, Mika
AU - Yoshida, Shinichiro
AU - Kojima, Minoru
AU - Takahashi, Hiroyuki
AU - Tomita, Akihiro
AU - Atsuta, Yoshiko
AU - Maruyama, Dai
AU - Tanaka, Eiji
AU - Suzuki, Takayo
AU - Kinoshita, Tomohiro
AU - Ogura, Michinori
AU - Ueda, Ryuzo
AU - Mizokami, Masashi
N1 - Funding Information:
This study was sponsored in part by a grant-in-aid from the Research Program on Hepatitis from the Japan Agency for Medical Research and Development (AMED) and a grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technology (Scientific Research (C) no. 90423855 to S.K.).
Funding Information:
Shigeru Kusumoto: Research funding from Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., and honoraria from Chugai Pharmaceutical Co., Ltd., Zennyaku Kogyo Co. Ltd., Bristol-Myers Squibb. Yasuhito Tanaka: Research funding from Fujifilim Corp., Gilead Sciences Inc., Bristol-Meyers Squibb, Chugai Pharmaceutical Co., Ltd., Fujifilim Corp., Janssen Pharmaceutical K.K, Glaxosmithkline pharmaceuticals ltd, Stanford Junior University and and Honoraria from Fujirebio Inc., Gilead Sciences Inc. Bristol-Meyers Squibb, Sysmex Corp. Ritsuro Suzuki: Honoraria from Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Bristol-Meyers Squib, Meiji Seika, MSD, Takeda, Celgene, Eisai, Ono Pharmaceuticals, Janssen, AbbVie, Novartis, Shionogi, Ohtsuka, Sawai, Sumitomo Dainippon, Alexion Pharma, Sanofi, Gilead Sciences, Jazz Pharma. Takashi Watanabe: Funding resources from TakaraBio and United Immunity, Co., Ltd., to support Department of Immuno-Gene Therapy in Mie University Graduate School of Medicine, to which TW belongs, and honoraria from Bristol-Meyers Squibb, AstraZeneca Pharmaceutical, and Chugai Pharmaceutical Co., Ltd. Rika Sakai: Research funding from Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Ono Pharmaceuticals, Yakult, Taiho Pharma, and Eisai and honoraria from Takeda, Bayer, Bristol-Meyer-Squibb, Sumitomo Dainippon, Celgene, Mundipharma, Eisai, and Kyowa Kirin Co., Ltd. Kuniaki Itoh: Consultant or Advisory Role on Zennyaku Kogyo Co. Ltd. Kisato Nosaka: Honoraria from Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Bristol-Myers Squibb, Celgene K.K. Masashi Sawa: Honoraria from Chugai, Pfizer, Astellas, Nippon-Shinyaku, Ono, MSD, Bristol-Myers Squibb, Kyowa-Hakko Kirin, Asahi-Kasei, Novartis, Eisai, Otsuka, Sumitomo Dainippon, Sanofi, Takeda, Celgene, Mochida, Shire, Mundipharma. Rumiko Okamoto: Honoraria from Kissei, Celgene, Chugai. Toshiki Uchida: Honoraria from Pfizer, Chugai Pharmaceutical, Takeda Pharmaceutical, Janssen Pharmaceutical, Eisai, Celgene, Mundipfarma, Bristol-Myers Squibb, Ono Pharmaceutical, Novartis Pharma, Otsuka Pharmaceutical, Nippon Shinyaku, Kyowa Kirin. Masataka Okamoto: Research funding from Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Taiho Pharma, Takeda Pharmaceutical Co. Ltd., Ono Pharmaceutical Co., Ltd. Yasushi Onishi: Research funding from Takeda, Bristol-Myers Squibb, MSD, and honoraria from Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Bristol-Myers Squibb, Pfizer, Astellas, Novartis, Celgene, Sumitomo Dainippon, Ono, Nippon Shinyaku, Janssen. Otsuka, MSD. Hiroyuki Takahashi: Consultant or Advisory role on Celgene, Takeda, Chugai Pharmaceutical Co., Ltd., honoraria from Kyowa Kirin Co., Ltd., Bristol-Meyers Squibb, Novartis, Ono, Janssen. Akihiro Tomita: Research funding from Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Taiho Pharma, and honoraria from Chugai Pharmaceutical Co., Ltd. Yoshiko Atsuta: Honoraria from Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Mochida, Meiji Seika, Bristol-Myers Squibb, Yakult Honsha, Janssen. Dai Maruyama: Research funding from Chugai Pharmaceutical Co., Ltd., Zennyaku Kogyo Co. Ltd., Ono Pharmaceutical, Celgene, Takeda Pharmaceutical, Janssen Pharmaceutical, Bristol-Myers Squibb, Merck, Amgen Astellas BioPharma, Astellas Pharma, Sanofi, Novartis Pharma, Otsuka Pharmaceutical and honoraria from Chugai Pharmaceutical Co., Ltd., Zennyaku Kogyo Co. Ltd., Ono Pharmaceutical, Celgene, Takeda Pharmaceutical, Janssen Pharmaceutical, Eisai, Kyowa Hakko Kirin, Bristol-Myers Squibb, SYNMOSA BIOPHARMA, NIPPON SHINYAKU. Eiji Tanaka: Honoraria from Sysmex Corporation. Tomohiro Kinoshita: Research funding from Takeda, Chugai, Ono, MSD, Eisai, Gilead, Zenyaku, Soleisia, and honoraria from Takeda, Chugai, Ono.
PY - 2020/8
Y1 - 2020/8
N2 - Background & Aims: HBV reactivation is a risk in patients receiving anti-CD20 antibodies for the treatment of lymphoma. The purpose of this post hoc analysis was to evaluate the efficacy of an ultra-high sensitivity HBsAg assay to guide preemptive antiviral treatment in patients with lymphoma and resolved HBV infections using prospectively stored samples from an HBV DNA monitoring study. Methods: HBV reactivation (defined as HBV DNA levels of ≥11 IU/ml) was confirmed in 22 of 252 patients. A conventional HBsAg assay (ARCHITECT, cut-off value: 0.05 IU/ml) and an ultra-high sensitivity HBsAg assay employing a semi-automated immune complex transfer chemiluminescence enzyme technique (ICT-CLEIA, cut-off value: 0.0005 IU/ml) were performed at baseline, at confirmed HBV reactivation and monitored after HBV reactivation. Results: Baseline HBsAg was detected using ICT-CLEIA in 4 patients; in all of whom precore mutants with high replication capacity were reactivated. Of the 6 patients with HBV DNA detected below the level of quantification at baseline, 5 showed HBV reactivation and 3 of the 5 had precore mutations. Sensitivity for detection by ARCHITECT and ICT-CLEIA HBsAg assays at HBV reactivation or the next sampling after HBV reactivation was 18.2% (4 of 22) and 77.3% (17 of 22), respectively. Of the 5 patients undetectable by ICT-CLEIA, HBV reactivation resolved spontaneously in 2 patients. All 6 patients reactivated with precore mutations including preS deletion could be diagnosed by ICT-CLEIA HBsAg assay at an early stage of HBV reactivation. Multivariate analysis showed that an anti-HBs titer of less than 10 mIU/ml, HBV DNA detected but below the level of quantification, and HBsAg detected by ICT-CLEIA at baseline were independent risk factors for HBV reactivation (adjusted hazard ratios, 15.4, 31.2 and 8.7, respectively; p <0.05). Conclusions: A novel ICT-CLEIA HBsAg assay is an alternative method to diagnose HBV reactivation. Clinical trial number: UMIN000001299. Lay summary: Hepatitis B virus can be reactivated in lymphoma patients receiving anti-CD20 antibodies such as rituximab. Currently, reactivation requires the monitoring of HBV DNA, but monitoring of the surface antigen (HBsAg) could provide a relatively inexpensive, quick and easy alternative. We assessed the performance of an ultra-high sensitivity HBsAg assay and showed that it could be effective for the diagnosis and monitoring of HBV reactivation.
AB - Background & Aims: HBV reactivation is a risk in patients receiving anti-CD20 antibodies for the treatment of lymphoma. The purpose of this post hoc analysis was to evaluate the efficacy of an ultra-high sensitivity HBsAg assay to guide preemptive antiviral treatment in patients with lymphoma and resolved HBV infections using prospectively stored samples from an HBV DNA monitoring study. Methods: HBV reactivation (defined as HBV DNA levels of ≥11 IU/ml) was confirmed in 22 of 252 patients. A conventional HBsAg assay (ARCHITECT, cut-off value: 0.05 IU/ml) and an ultra-high sensitivity HBsAg assay employing a semi-automated immune complex transfer chemiluminescence enzyme technique (ICT-CLEIA, cut-off value: 0.0005 IU/ml) were performed at baseline, at confirmed HBV reactivation and monitored after HBV reactivation. Results: Baseline HBsAg was detected using ICT-CLEIA in 4 patients; in all of whom precore mutants with high replication capacity were reactivated. Of the 6 patients with HBV DNA detected below the level of quantification at baseline, 5 showed HBV reactivation and 3 of the 5 had precore mutations. Sensitivity for detection by ARCHITECT and ICT-CLEIA HBsAg assays at HBV reactivation or the next sampling after HBV reactivation was 18.2% (4 of 22) and 77.3% (17 of 22), respectively. Of the 5 patients undetectable by ICT-CLEIA, HBV reactivation resolved spontaneously in 2 patients. All 6 patients reactivated with precore mutations including preS deletion could be diagnosed by ICT-CLEIA HBsAg assay at an early stage of HBV reactivation. Multivariate analysis showed that an anti-HBs titer of less than 10 mIU/ml, HBV DNA detected but below the level of quantification, and HBsAg detected by ICT-CLEIA at baseline were independent risk factors for HBV reactivation (adjusted hazard ratios, 15.4, 31.2 and 8.7, respectively; p <0.05). Conclusions: A novel ICT-CLEIA HBsAg assay is an alternative method to diagnose HBV reactivation. Clinical trial number: UMIN000001299. Lay summary: Hepatitis B virus can be reactivated in lymphoma patients receiving anti-CD20 antibodies such as rituximab. Currently, reactivation requires the monitoring of HBV DNA, but monitoring of the surface antigen (HBsAg) could provide a relatively inexpensive, quick and easy alternative. We assessed the performance of an ultra-high sensitivity HBsAg assay and showed that it could be effective for the diagnosis and monitoring of HBV reactivation.
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U2 - 10.1016/j.jhep.2020.03.009
DO - 10.1016/j.jhep.2020.03.009
M3 - Article
C2 - 32194183
AN - SCOPUS:85085692309
VL - 73
SP - 285
EP - 293
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 2
ER -