Wang J, Yu Y, Li G, Shen C, Li J, Chen S, Zhang X, Zhu M, Zheng J, Song Z, Wu J, Shao L, Meng Z, Wang X, Huang Y, Zhang J, Qiu C, Zhang W
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Department of Hepatology, The Second Hospital of Yinzhou of Ningbo, Ningbo, China.
J Viral Hepat. 2018 Sep;25(9):1038-1047. doi: 10.1111/jvh.12908. Epub 2018 May 9.
Virus-like particles encapsulating HBV-RNA represent a serum biomarker for assessing viral replication activity in clinical practice. However, baseline levels of serum HBV-RNA and their associations with viral replicative intermediates and liver disease in phases of chronic hepatitis B remain unknown. In this cross-sectional study, 102 patients were categorized into immune-tolerant (IT), HBeAg-positive immune active (HBeAg+IA), inactive carrier (IC) and HBeAg-negative immune active (HBeAg-IA) phases. HBV-RNA in serum samples and in 66 paired liver biopsies were quantified and correlated with serum ALT levels, histopathological scores and the levels of other viral replicative intermediates. Mean levels of serum HBV-RNA differed among phases, with the highest levels among IT (6.78 ± 0.83 log copies mL ) patients, followed by HBeAg+IA (5.73 ± 1.16 log copies mL ), HBeAg-IA (4.52 ± 1.25 log copies mL ) and IC (2.96 ± 0.40 log copies mL ) patients. Serum HBV-RNA levels correlated with HBV DNA in all phases, although correlations with other viral replicative intermediates weakened or disappeared when cases were stratified into phases. Distinct compositions of viral products were found among phases: the ratio of HBsAg to serum HBV-RNA was highest in IC patients, while the ratio of serum HBV-RNA to intrahepatic HBV-RNA and the ratio of intrahepatic HBV-DNA to intrahepatic HBV-RNA were significantly higher in IT patients. In conclusion, baseline levels of HBV-RNA and the composition of viral replicative intermediates differ significantly across the natural course of chronic HBV infection. These findings shed light on the nature of viral replication and pathogenesis of disease among different phases of chronic HBV infection.
包裹乙肝病毒RNA的病毒样颗粒是临床实践中评估病毒复制活性的血清生物标志物。然而，慢性乙型肝炎各阶段血清乙肝病毒RNA的基线水平及其与病毒复制中间体和肝脏疾病的关联仍不清楚。在这项横断面研究中，102例患者被分为免疫耐受期（IT）、HBeAg阳性免疫活跃期（HBeAg+IA）、非活动携带者期（IC）和HBeAg阴性免疫活跃期（HBeAg-IA）。对血清样本和66例配对肝活检组织中的乙肝病毒RNA进行定量，并与血清ALT水平、组织病理学评分以及其他病毒复制中间体的水平进行相关性分析。各阶段血清乙肝病毒RNA的平均水平有所不同，IT期患者（6.78±0.83 log拷贝/mL）最高，其次是HBeAg+IA期（5.73±1.16 log拷贝/mL）、HBeAg-IA期（4.52±1.25 log拷贝/mL）和IC期患者（2.96±0.40 log拷贝/mL）。各阶段血清乙肝病毒RNA水平均与乙肝病毒DNA相关，不过当病例按阶段分层时，与其他病毒复制中间体的相关性减弱或消失。各阶段病毒产物的组成不同：IC期患者中HBsAg与血清乙肝病毒RNA的比值最高，而IT期患者中血清乙肝病毒RNA与肝内乙肝病毒RNA的比值以及肝内乙肝病毒DNA与肝内乙肝病毒RNA的比值显著更高。总之，在慢性乙肝病毒感染的自然病程中，乙肝病毒RNA的基线水平和病毒复制中间体的组成存在显著差异。这些发现揭示了慢性乙肝病毒感染不同阶段病毒复制的本质和疾病的发病机制。
