Clinical efficacy of a novel, high-sensitivity HBcrAg assay in the management of chronic hepatitis B and HBV reactivation.

Abstract Background & Aims A fully automated, novel high-sensitivity hepatitis B core-related antigen assay (iTACT-HBcrAg) has been developed. We demonstrate the clinical utility of iTACT-HBcrAg for monitoring chronic hepatitis B (CHB) and early detection of hepatitis B virus (HBV) reactivation. Methods After fundamental assessments, the clinical performance of iTACT-HBcrAg was compared with other HBV markers. 1) Of our CHB patients, serial sera, available from 161 HBeAg-negative CHB patients with persistently undetectable HBV DNA, were measured by iTACT-HBcrAg and a conventional HBcrAg assay (G-HBcrAg). 2) Serial sera from 13 HBV-reactivated patients were measured by iTACT-HBcrAg and ultra-high-sensitivity hepatitis B surface antigen (HBsAg) immune complex transfer-chemiluminescent enzyme immunoassay (lower limit of detection; 0.0005 IU/mL, ICT-CLEIA) for comparison with HBV DNA detection. 3) To elucidate the various HBcrAg components iTACT-HBcrAg detected, OptiPrep density gradient centrifugation analysis was performed on sera obtained before and after HBV reactivation. Results The analytical performance of iTACT-HBcrAg was satisfactory. The sensitivity of iTACT-HBcrAg (2.1 Log U/mL) was approximately 10-fold greater than that of G-HBcrAg (2.8 Log U/mL). 1) HBcrAg was detectable in 97.5% (157/161) sera of CHB patients by iTACT-HBcrAg, of which 75.2% (121/161) had ≥2.8 Log U/mL HBcrAg; and 22.4% (36/161) had 2.1-2.8 Log U/mL HBcrAg, which was undetectable by G-HBcrAg. 2) Nine and 2 of 13 HBV-reactivated patients were HBcrAg-positive by iTACT-HBcrAg before and at HBV DNA positivity, respectively. Seven and 4 were HBcrAg-positive by iTACT-HBcrAg before and at being HBsAg-positive by ICT-CLEIA, respectively. 3) The HBcrAg detected before HBV reactivation by iTACT-HBcrAg was contained in empty particles (22-KDa precore protein). Conclusions iTACT-HBcrAg should be of increased benefit for monitoring novel anti-HBV treatments for HBeAg-negative patients and early detection of HBV reactivation.