Objective To investigate the correlations of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) level in liver tissue with serum viral markers,HBV DNA levels,and pathological changes of liver tissue in patients with chronic HBV infection,and to provide a theoretical basis for evaluating the efficacy and determining the course of antiviral therapy.Methods Thirty patients with chronic HBV infection who were hospitalized from May 2007 to February 2008 were included in the study.The HBV cccDNA in liver tissue,total HBV DNA (HBV tDNA) in liver tissue,and serum HBV DNA were quantified by real-time quantitative polymerase chain reaction; the HBsAg and HBeAg in serum were quantified by chemiluminescence immunoassay.The correlations of HBV cccDNA level in liver tissue with HBV tDNA level in liver tissue,serum HBV DNA level,serum HBsAg and HBeAg levels,and the inflammation activity and fibrosis degree of liver tissue were analyzed ; Pearson's simple correlation coefficient and Spearman's rank correlation coefficient were used for correlation analysis.Results HBV cccDNA was detected in all the 30 patients with chronic HBV infection,with a content ranging from 3.15 × 103 to 1.06 × 107 copies/mg.The HBV cccDNA level in liver tissue had a positive correlation with HBV tDNA level in liver tissue (r =0.375,P ＜ 0.05),but had no correlation with serum HBV DNA level (r =0.174,P ＞0.05).The HBV cccDNA level in liver tissue had a highly positive correlation with serum HBsAg level (r =0.562,P ＜0.001),but had no correlation with serum HBeAg level (r =0.152,P ＞0.05).The HBV cccDNA level in liver tissue was not correlated with the inflammation activity and fibrosis degree of liver tissue (r =0.082,P ＞0.05).Conclusion The replication of HBV cccDNA is stable and moderate in patients with chronic HBV infection.Serum HBV DNA load cannot directly represent the HBV cccDNA level in liver tissue; serum HBsAg level can be used as an indicator of HBV cccDNA level in liver tissue.%目的 探讨慢性HBV感染者肝组织中HBV cccDNA含量与血清病毒标志物、HBV DNA及肝脏病理分级的关系,为临床评价抗病毒治疗效果及疗程确定提供理论依据.方法 以2007年5月-2008年2月住院的30例慢性HBV感染者为研究对象,应用实时荧光定量聚合酶链反应(RT-PCR)方法检测患者肝组织中HBV cccDNA、肝组织总HBV DNA(HBVtDNA)和血清HBVDNA,同时用化学发光免疫分析法检测HBsAg、HBeAg定量,分析感染者肝组织内HBV cccDNA与肝组织内HBV DNA、血清HBVDNA、HBsAg及HBeAg定量水平之间的关系,并比较肝组织中HBVcccDNA含量与肝脏病理炎症和纤维化分级的关系.采用Pearson简单相关和Spearman等级相关法进行相关性分析.结果 30例慢性HBV感染者肝组织中均可检出HBV cccDNA,范围在3.15 ×103 ～1.06 ×107拷贝/mg;肝组织cccDNA定量与肝组织总HBV DNA定量呈正相关(r=0.375,P＜0.05),与血清HBV DNA无相关性(r=0.174,P＞0.05)；肝组织中HBV cccDNA水平与血清HBsAg定量呈高度正相关(r=0.562,P＜0.001),而与血清HBeAg定量无相关性(r=0.152,P＞0.05).肝组织cccDNA定量与肝组织炎症活动度(G)及纤维化程度(S)无相关性(r=0.082,P ＞0.05).结论 慢性HBV感染者肝组织内HBVcccDNA成稳定的中等水平复制；血清HBV DNA载量不能直接代表其肝组织中的HBV cccDNA水平；血清HBsAg定量可作为反映肝组织中HBV cccDNA水平的指标.
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