Ultra-high sensitivity HBsAg assay can diagnose HBV reactivation following rituximab-based therapy in patients with lymphoma

Shigeru Kusumoto, Yasuhito Tanaka, Ritsuro Suzuki, Takashi Watanabe, Masanobu Nakata, Rika Sakai, Noriyasu Fukushima, Takuya Fukushima, Yukiyoshi Moriuchi, Kuniaki Itoh, Kisato Nosaka, Ilseung Choi, Masashi Sawa, Rumiko Okamoto, Hideki Tsujimura, Toshiki Uchida, Sachiko Suzuki, Masataka Okamoto, Tsutomu Takahashi, Isamu SugiuraYasushi Onishi, Mika Kohri, Shinichiro Yoshida, Minoru Kojima, Hiroyuki Takahashi, Akihiro Tomita, Yoshiko Atsuta, Dai Maruyama, Eiji Tanaka, Takayo Suzuki, Tomohiro Kinoshita, Michinori Ogura, Ryuzo Ueda, Masashi Mizokami

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Abstract

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.

Original languageEnglish
Pages (from-to)285-293
Number of pages9
JournalJournal of Hepatology
Volume73
Issue number2
DOIs
Publication statusPublished - 08-2020

All Science Journal Classification (ASJC) codes

  • Hepatology

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    Kusumoto, S., Tanaka, Y., Suzuki, R., Watanabe, T., Nakata, M., Sakai, R., Fukushima, N., Fukushima, T., Moriuchi, Y., Itoh, K., Nosaka, K., Choi, I., Sawa, M., Okamoto, R., Tsujimura, H., Uchida, T., Suzuki, S., Okamoto, M., Takahashi, T., ... Mizokami, M. (2020). Ultra-high sensitivity HBsAg assay can diagnose HBV reactivation following rituximab-based therapy in patients with lymphoma. Journal of Hepatology, 73(2), 285-293. https://doi.org/10.1016/j.jhep.2020.03.009