治疗初治慢性乙型肝炎病毒感染患者不同阶段的 HBV 新型血清标志物特征。
Characteristics of HBV Novel Serum Markers across Distinct Phases in Treatment-Naïve Chronic HBV-Infected Patients.
机构信息
Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518035 Guangdong Province, China.
Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China.
出版信息
Dis Markers. 2022 Jul 14;2022:4133283. doi: 10.1155/2022/4133283. eCollection 2022.
METHODS
A total of 111 patients in total from different disease phases were recruited, including 21 in immune-tolerant (IT) phase, 49 in immune-clearance (IC) phases, 29 in immune-control or low replicative (LR) phase, and 12 in reactivation phases. Serum HBV RNA, anti-HBc, HBcrAg, and intrahepatic covalently closed circular DNA (cccDNA) were quantified and each of these indicator's correlation with liver inflammation was analyzed.
RESULTS
HBeAg-positive individuals had significant higher serum levels of HBV RNA and HBcrAg than those who were HBeAg negative, similar to that of serum HBV DNA. Comparatively, HBV RNA ( =0.79, < 0.01) and HBcrAg ( =0.78, < 0.01) had almost same higher overall correlation with the cccDNA, as that of HBV DNA ( =0.81, < 0.01). Serum anti-HBc level ( = -0.52, < 0.05) is negatively correlated with cccDNA level at IT phase rather than the other three phases. When set the cutoff value at 4.00 log IU/mL, serum anti-HBc showed potential to indicate liver inflammation, with AUC as 0.79 and the specificities as 78.85% for HBeAg positive, and with AUC as 0.72 and the specificities as 62.16% for HBeAg-negative patients, respectively.
CONCLUSIONS
In treatment-naïve patients, levels of serological markers HBV RNA and HBcrAg could mirror intrahepatic cccDNA level, but were not superior to HBV DNA level. Serum anti-HBc level had certain potential to be used as a predicting marker for liver inflammation.
方法
共招募了 111 名来自不同疾病阶段的患者，包括 21 名免疫耐受（IT）期患者、49 名免疫清除（IC）期患者、29 名免疫控制或低复制（LR）期患者和 12 名再激活期患者。定量检测血清 HBV RNA、抗-HBc、HBcrAg 和肝内共价闭合环状 DNA（cccDNA），分析这些指标与肝炎症的相关性。
结果
HBeAg 阳性个体的血清 HBV RNA 和 HBcrAg 水平显著高于 HBeAg 阴性个体，与血清 HBV DNA 相似。相比之下，HBV RNA（ =0.79，<0.01）和 HBcrAg（ =0.78，<0.01）与 cccDNA 的总体相关性几乎相同，与 HBV DNA（ =0.81，<0.01）相似。血清抗-HBc 水平（ = -0.52，<0.05）在 IT 期与 cccDNA 水平呈负相关，而在其他三个阶段则无相关性。当将血清抗-HBc 的截断值设定为 4.00 log IU/mL 时，其对 HBeAg 阳性患者的肝炎症具有潜在的指示作用，AUC 为 0.79，特异性为 78.85%，对 HBeAg 阴性患者的 AUC 为 0.72，特异性为 62.16%。
结论
在未经治疗的患者中，血清学标志物 HBV RNA 和 HBcrAg 的水平可以反映肝内 cccDNA 水平，但并不优于 HBV DNA 水平。血清抗-HBc 水平具有一定的潜力作为肝炎症的预测标志物。
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