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

BACKGROUND & AIMS: The purpose of this post hoc analysis was to evaluate the efficacy of an ultra-high sensitive HBsAg assay using prospectively stored samples of HBV DNA monitoring study for lymphoma patients with resolved HBV infection following anti-CD20 antibody, rituximab-containing chemotherapy (UMIN000001299).

METHODS: HBV reactivation defined as HBV DNA levels of 11 IU/mL or more was confirmed in 22 of 252 patients. Conventional HBsAg assay (ARCHITECT, cut-off value: 0.05 IU/mL) and ultra-high sensitive HBsAg assay employing a semi-automated immune complex transfer chemiluminescence enzyme technique (ICT-CLEIA, cut-off value: 0.0005 IU/mL) were measured 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 discrepant 5 patients undetectable by ICT-CLEIA, 2 patients resolved spontaneously. 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, detected HBV DNA below the level of quantification, and detected ICT-CLEIA HBsAg 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 would be an alternative method to diagnose HBV reactivation.