乙型肝炎患者抗病毒治疗过程中肝组织HBV cccDNA与血清学标志物变化的动态变化研究

Dynamic observation on hepatitis B virus cccDNA in liver tissue and serological markers changes in the process of antiviral therapy

目的探讨慢性乙型病毒性肝炎患者抗病毒治疗过程中肝组织乙型肝炎病毒(HBV)共价闭合环状DNA(cccDNA)与相关血清学标志物变化。方法 88例乙型肝炎e抗原(HBeAg)阳性的慢性乙型病毒性肝炎患者给予恩替卡韦抗病毒治疗96周。分别于0、24周、48周、96周检测肝组织中和血清HBV cccDNA、血清HBV DNA、乙型肝炎表面抗原(HBs Ag)、HBeAg定量,并分析肝组织HBV cccDNA与血清学标志物变化的关系。结果与基线比较,治疗后24周时患者肝组织HBV cccDNA,血清HBV cccDNA,血清HBV DNA和HBs Ag均显著降低(P<0.05或P<0.01);治疗后24周和48周比较:肝组织HBV cccDNA,血清HBV cccDNA,血清HBV DNA差异有统计学意义(P<0.01);48周与96周检测指标相比:肝组织HBV cccDNA定量差异无统计学意义(P>0.05);血清HBV DNA定量和血清HBV cccDNA定量差异有统计学意义(P<0.01)。血清HBs Ag和HBeAg差异无统计学意义(P>0.05)。结论血清HBV DNA定量和血清HBV cccDNA定量同步下降幅度大于肝组织cccDNA定量和HBs Ag、HBeAg定量,肝组织HBV cccDNA定量、HBs Ag、HBeAg定量在48周后逐步趋于稳定。血清HBs Ag、HBeAg定量与肝组织HBV cccDNA具有较高的一致性,血清HBs Ag、HBeAg定量检测能更准确、方便、快捷指导临床诊断。

Objective To explore hepatitis B virus（ HPV） covalently closed circular DNA（ cccDNA） of liver tissue and levels of relative serological markers,including serum HBV cccDNA and serum HBV DNA and epatitis B surface antigen（ HBs Ag） quantitative and hepatitis B Antigen（ HBeAg）quantitative in chronic hepatitis B（ CHB） patients after antiviral treatment. Methods Eighty-eight HBeAg positive CHB viral hepatitis patients received entecavir antiviral treatment for 96 weeks. Their HBV cccDNA in liver tissue and serum HBV cccDNA,serum HBV DNA and HBs Ag and HBeAg quantitative were detected respectively in 0,24,48 and 96 weeks. The relationship between liver tissue HBV cccDNA and serological markers was evaluated dynamically. Results Compared with the baseline,levels of HBV cccDNA in liver tissue,serum HBV cccDNA,HBV DNA and Hbs Ag decreased significantly at 24 weeks after treatment（ P〈0. 05 or P〈0. 01）. Levels of HBV cccDNA in liver tissue,serum HBV cccDNA and HBV DNA kept declined at 48 weeks（ P〈0. 01）. There was no significant difference in HBV cccDNA of liver tissue between 48 weeks and 96 weeks（ P〈0. 05）. Compared with those at 48 weeks,the serum HBV DNA and serum HBV cccDNA quantitative reduced significantly at 96 weeks（ P〈0. 01）. There were no significant differences in serum HBs Ag and HBeAg quantitative between 48 weeks and 96 weeks（ P〉0. 05）.Conclusion The findings indicate a higher synchronous declined in serum HBV DNA and serum HBV cccDNA quantitative than HBV cccDNA of liver tissue,serum HBs Ag and HBeAg quantitative.Changes in HBV cccDNA of liver tissue,serum HBs Ag and HBeAg quantitative are stabilized since 48 weeks after treatment,which may reveal a consistency between them. Quantitative detection of serum HBs Ag and HBeAg may be more accurate,convenient and fast for guiding the clinical diagnosis.