Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, P.R. China.
Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, P.R. China.
Sci Rep. 2017 Mar 14;7(1):173. doi: 10.1038/s41598-017-00111-0.
Recently, hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. This study aimed to investigate whether serum quantitative HBcrAg (qHBcrAg) was a satisfactory surrogate marker of intrahepatic covalently closed circular DNA (cccDNA). A total of 139 patients with liver biopsy were enrolled, consisting of 59 patients in immune tolerance (IT) phase, 52 patients in immune clearance (IC) phase, 18 patients in low-replication (LR) phase, and 10 patients in reactivation phase. All patients in IC phase have received entecavir (ETV) therapy, and 32 of them undergone a second liver biopsy at 24 months. Among those patients, qHBcrAg was strongly correlated with intrahepatic cccDNA, which is superior to that of qHBsAg and HBV DNA. And similar findings were also observed in patients in IT, IC, LR and reactivation phases. Among the 32 ETV-treated patients with a second liver biopsy in IC phase, the decline of intrahepatic cccDNA was accompanied by changes in both qHBcrAg and qHBsAg. However, as compared to qHBsAg, the change of qHBcrAg was more strongly associated with intrahepatic cccDNA-decline. In summary, serum qHBcrAg should be a satisfactory surrogate of intrahepatic HBV cccDNA in CHB patients.
最近，乙型肝炎核心相关抗原（HBcrAg）被认为是乙型肝炎病毒（HBV）感染的另一个标志物。本研究旨在探讨血清定量 HBcrAg（qHBcrAg）是否可作为乙型肝炎患者肝内共价闭合环状 DNA（cccDNA）的替代标志物。共纳入 139 例肝活检患者，包括免疫耐受（IT）期 59 例、免疫清除（IC）期 52 例、低复制（LR）期 18 例和再激活期 10 例。IC 期所有患者均接受恩替卡韦（ETV）治疗，其中 32 例在 24 个月时进行第二次肝活检。在这些患者中，qHBcrAg 与肝内 cccDNA 强烈相关，优于 qHBsAg 和 HBV DNA。在 IT、IC、LR 和再激活期患者中也观察到类似的结果。在 32 例接受 ETV 治疗的 IC 期第二次肝活检患者中，肝内 cccDNA 的下降伴随着 qHBcrAg 和 qHBsAg 的变化。然而，与 qHBsAg 相比，qHBcrAg 的变化与肝内 cccDNA 下降的相关性更强。总之，血清 qHBcrAg 应该是 CHB 患者肝内 HBV cccDNA 的满意替代标志物。
