Suzuki Fumitaka, Hosaka Tetsuya, Imaizumi Masayasu, Kobayashi Mariko, Ohue Chiharu, Suzuki Yoshiyuki, Fujiyama Shunichiro, Kawamura Yusuke, Sezaki Hitomi, Akuta Norio, Kobayashi Masahiro, Saitoh Satoshi, Arase Yasuji, Ikeda Kenji, Kumada Hiromitsu
Department of Hepatology, Toranomon Hospital, Minato-ku, Tokyo, Japan.
Product Development Department, Fujirebio Inc, Hachioji, Tokyo, Japan.
Hepatol Res. 2021 Apr;51(4):426-435. doi: 10.1111/hepr.13602. Epub 2021 Mar 6.
Hepatitis B surface antigen (HBsAg) seroclearance indicates a "functional cure" in chronic hepatitis B (CHB) virus infection. However, several cases of hepatocellular carcinoma (HCC) development have been reported after HBsAg seroclearance. We evaluated the potential of HBsAg and hepatitis B core-related antigen (HBcrAg), measured by the ultra-highly sensitive assays, in cases with HCC development after HBsAg seroclearance.
We enrolled 17 patients with CHB who achieved HBsAg seroclearance, defined by the conventional assay using Architect HBsAg QT kit (five HCC patients and 12 non-HCC patients). HBsAg and HBcrAg were measured in their stored serum samples using ultra-highly sensitive assays featuring "immunoassay for total antigen including complex via pretreatment (iTACT)" technology.
All five patients who developed HCC were positive for HBsAg or HBcrAg by iTACT-HBsAg or iTACT-HBcrAg at all follow-up points. HBcrAg levels in the HCC group, using iTACT-HBcrAg, were significantly higher than those in the non-HCC group at HBsAg seroclearance (3.6 LogU/ml (2.8-4.2) versus 2.6 (<2.1-3.8), p = 0.020). The best cutoff value of iTACT-HBcrAg for predicting HCC development was 2.7 LogU/ml by receiver operating characteristic curve analysis. The prevalence of HBcrAg ≥2.7 in the HCC group was significantly higher than that in non-HCC group (100% [5/5] versus 33% [4/12], p = 0.029).
Residual low viral antigen might predict HCC development even if HBsAg seroclearance was achieved according to a conventional assay. The results suggest that iTACT assays of HBsAg and HBcrAg would be useful for monitoring CHB patients.
乙肝表面抗原（HBsAg）血清学清除表明慢性乙型肝炎（CHB）病毒感染实现了“功能性治愈”。然而，已有数例HBsAg血清学清除后发生肝细胞癌（HCC）的病例报道。我们评估了通过超高灵敏度检测法检测的HBsAg和乙肝核心相关抗原（HBcrAg）在HBsAg血清学清除后发生HCC病例中的潜在作用。
我们纳入了17例实现HBsAg血清学清除的CHB患者，采用Architect HBsAg QT试剂盒的传统检测法进行定义（5例HCC患者和12例非HCC患者）。使用具有“包括预处理复合物的总抗原免疫测定（iTACT）”技术的超高灵敏度检测法，在其储存的血清样本中检测HBsAg和HBcrAg。
所有5例发生HCC的患者在所有随访时间点通过iTACT - HBsAg或iTACT - HBcrAg检测，HBsAg或HBcrAg均为阳性。在HBsAg血清学清除时，使用iTACT - HBcrAg检测，HCC组的HBcrAg水平显著高于非HCC组（3.6 LogU/ml（2.8 - 4.2）对2.6（<2.1 - 3.8），p = 0.020）。通过受试者工作特征曲线分析，iTACT - HBcrAg预测HCC发生的最佳截断值为2.7 LogU/ml。HCC组中HBcrAg≥2.7的患病率显著高于非HCC组（100%[5/5]对33%[4/12]，p = 0.029）。
即使根据传统检测法实现了HBsAg血清学清除，残留的低病毒抗原仍可能预测HCC的发生。结果表明，HBsAg和HBcrAg的iTACT检测法对监测CHB患者将是有用的。
