Inoue Takako, Kusumoto Shigeru, Iio Etsuko, Ogawa Shintaro, Suzuki Takanori, Yagi Shintaro, Kaneko Atsushi, Matsuura Kentaro, Aoyagi Katsumi, Tanaka Yasuhito
Department of Clinical Laboratory Medicine, Nagoya City University Hospital, Nagoya, Japan.
Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
J Hepatol. 2021 Aug;75(2):302-310. doi: 10.1016/j.jhep.2021.02.017. Epub 2021 Mar 21.
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 for the early detection of HBV reactivation.
After fundamental assessments, the clinical performance of iTACT-HBcrAg was compared with other HBV markers. i) Serial sera, available from 161 HBeAg-negative patients with CHB and persistently undetectable HBV DNA, were measured by iTACT-HBcrAg and a conventional HBcrAg assay (G-HBcrAg). ii) Serial sera from 13 HBV-reactivated patients were measured by iTACT-HBcrAg and an ultra-high-sensitivity HBsAg immune complex transfer-chemiluminescent enzyme immunoassay (lower limit of detection; 0.0005 IU/ml, ICT-CLEIA) to compare HBV DNA detection. iii) To elucidate the various HBcrAg components detected by iTACT-HBcrAg, OptiPrep density gradient centrifugation analysis was performed on sera obtained before and after HBV reactivation.
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). i) HBcrAg was detectable in the sera of 97.5% (157/161) of patients with CHB by iTACT-HBcrAg, of whom 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. ii) 9 and 2 of 13 HBV-reactivated patients were HBcrAg-positive by iTACT-HBcrAg before and at HBV DNA positivity, respectively; 7 and 4 were HBcrAg-positive by iTACT-HBcrAg before and at HBsAg-positivity by ICT-CLEIA, respectively. iii) The HBcrAg detected by iTACT-HBcrAg before HBV reactivation was contained in empty particles (22 KDa precore protein).
iTACT-HBcrAg could be used to better monitor responses to anti-HBV treatments in HBeAg-negative patients and for the early detection of HBV reactivation.
A fully automated, novel high-sensitivity hepatitis B core-related antigen assay (iTACT-HBcrAg) has been developed. iTACT-HBcrAg can be used to monitor HBeAg-negative patients with chronic hepatitis B, as well as for the early detection of HBV reactivation. iTACT-HBcrAg could be used as a general marker of disease progression and treatment response.
已研发出一种全自动、新型的高灵敏度乙型肝炎核心相关抗原检测方法（iTACT-HBcrAg）。我们证明了iTACT-HBcrAg在监测慢性乙型肝炎（CHB）及早期检测HBV再激活方面的临床应用价值。
在进行基础评估后，将iTACT-HBcrAg的临床性能与其他HBV标志物进行比较。i）采用iTACT-HBcrAg和传统的HBcrAg检测方法（G-HBcrAg）对161例HBeAg阴性的CHB患者且HBV DNA持续检测不到的系列血清进行检测。ii）采用iTACT-HBcrAg和超高度灵敏的HBsAg免疫复合物转移化学发光酶免疫分析法（检测下限；0.0005 IU/ml，ICT-CLEIA）对13例HBV再激活患者的系列血清进行检测，以比较HBV DNA检测情况。iii）为阐明iTACT-HBcrAg检测到的各种HBcrAg成分，对HBV再激活前后获取的血清进行OptiPrep密度梯度离心分析。
iTACT-HBcrAg的分析性能令人满意。iTACT-HBcrAg的灵敏度（2.1 Log U/ml）比G-HBcrAg（2.8 Log U/ml）高约10倍。i）通过iTACT-HBcrAg检测，97.5%（157/161）的CHB患者血清中可检测到HBcrAg，其中75.2%（121/161）的患者HBcrAg≥2.8 Log U/ml，22.4%（36/161）的患者HBcrAg为2.1 - 2.8 Log U/ml，而G-HBcrAg检测不到这些患者的HBcrAg。ii）13例HBV再激活患者中，分别有9例和2例在HBV DNA阳性之前和之时通过iTACT-HBcrAg检测为HBcrAg阳性；分别有7例和4例在通过ICT-CLEIA检测HBsAg阳性之前和之时通过iTACT-HBcrAg检测为HBcrAg阳性。iii）在HBV再激活之前通过iTACT-HBcrAg检测到的HBcrAg存在于空颗粒（22 KDa前核心蛋白）中。
iTACT-HBcrAg可用于更好地监测HBeAg阴性患者对抗HBV治疗的反应以及早期检测HBV再激活。
已研发出一种全自动、新型的高灵敏度乙型肝炎核心相关抗原检测方法（iTACT-HBcrAg）。iTACT-HBcrAg可用于监测HBeAg阴性的慢性乙型肝炎患者，以及早期检测HBV再激活。iTACT-HBcrAg可作为疾病进展和治疗反应的通用标志物。
