慢性乙型肝炎抗病毒治疗后cccDNA持续转录活动的肝细胞的分子特征及其形成机制

The eradication of covalently closed circular DNA (cccDNA) is not feasible under the current antiviral agents. The inactivation of cccDNA-directed transcription is also difficult to achieve. In our preliminary study, we have demonstrated that HBV RNA were detectable in the liver biopsy samples of all patients after long-term nucleos(t)ide analogues (NUCs) therapy. On average, 50% of hepatocytes were HBV RNA positive. However, the molecular characteristics and formation mechanism of hepatocytes with persistent active cccDNA-directed transcription are still unknown. We intend to analyze the liver biopsy samples and serum of chronic hepatitis B patients receiving long-term NUCs or NUCs sequential combination with peginterferon-alfa (PegIFNa) by molecular biology, cytology and histology. We will further explore the molecular characteristics and formation mechanism of hepatocytes with persistent active cccDNA-directed transcription under different antiviral regimen. This will provide theoretical evidence for novel agents towards HBV cure.

现有的抗病毒治疗不能彻底清除肝细胞内的HBV共价闭合环状DNA（cccDNA），亦无法有效抑制cccDNA转录活性。我们的前期研究表明长期核苷（酸）类似物（NUCs）治疗后，所有患者的肝组织内均可测得HBV RNA，平均50%的肝细胞HBV RNA阳性。但是，长期抗病毒治疗后cccDNA持续转录活动的肝细胞的分子特征及其形成机制仍尚未明确。本课题将以接受长期NUCs治疗和NUCs序贯联合聚乙二醇干扰素（PegIFNa）的慢性乙型肝炎患者为主要研究对象，分子生物学、细胞学和组织学方法对肝组织和血清进行分析，阐明不同抗病毒治疗方案后cccDNA持续转录活动的肝细胞的分子特征及其形成机制，为实现HBV治愈的新药提供理论依据。

现有的抗病毒治疗不能彻底清除肝细胞内的HBV共价闭合环状DNA（cccDNA），亦无法有效抑制cccDNA转录活性。我们的前期研究表明长期核苷（酸）类似物（NUCs）治疗后，所有患者的肝组织内均可测得HBV RNA，平均50%的肝细胞HBV RNA阳性。但是，长期抗病毒治疗后cccDNA持续转录活动的肝细胞的分子特征及其形成机制仍尚未明确。本课题将以接受长期NUCs治疗和NUCs序贯联合聚乙二醇干扰素（PegIFNa）的慢性乙型肝炎患者为主要研究对象，分子生物学、细胞学和组织学方法对肝组织和血清进行分析，阐明不同抗病毒治疗方案后cccDNA持续转录活动的肝细胞的分子特征及其形成机制，为实现HBV治愈的新药提供理论依据。