慢性乙型肝炎患者肝细胞HBVccc DNA与血清HBV DNA及肝纤维化程度的相关性

Relationships among HBV ccc DNA in hepatocytes and HBV DNA in serum, severity of liver fibrosis in patients with chronic hepatitis B

目的探讨慢性乙型肝炎(CHB)患者肝细胞HBV ccc DNA含量与血清HBV DNA、肝组织纤维化程度的相关性及在抗病毒治疗中的临床意义。方法对48例未接受抗病毒治疗CHB患者(A组)和6例经聚乙二醇化干扰素α-2a规律抗病毒治疗48周CHB患者(B组)进行肝组织活检以检测肝纤维化分期,并应用real time-PCR检测肝细胞HBV ccc DNA含量。分析A组患者肝细胞HBV ccc DNA与肝纤维化程度以及两组患者肝细胞HBV ccc DNA与血清HBV DNA相关性,分析B组患者HBV ccc DNA变化。结果肝细胞cccDNA及血清DNA水平均与肝组织纤维化程度呈负相关,但HBV ccc DNA相关性更强(r=-0.465,P=0.008)。肝细胞HBV ccc DNA与血清HBV DNA不存在相关性(r=0.057,P=0.418)。B组患者肝细胞HBV ccc DNA较对照组(自A组中选取性别、年龄及HBV DNA无差异患者共12例)显著下降,其中3例患者血清HBV DNA载量低于检测下限,但肝细胞仍可检出HBV ccc DNA。结论肝细胞HBV ccc DNA与肝纤维程度呈负相关,而血清HBV DNA水平不能反映肝内病毒复制的程度。CHB患者抗病毒治疗需要长期进行才可能完全清除肝细胞内HBV ccc DNA。

Objective To explore the relationships among levels of HBV ccc DNA in hepatocytes, HBV DNA in serum and severity of liver fibrosis in patients with chronic hepatitis B （CHB）, and investigate its clinical significance in antiviral therapy. Methods There were two groups of patients： group A were CHB patients who did not accept any antiviral therapy before （n = 48）; group B were CHB patients who received antiviral treatment with peginterferon alpha-2a for 48 weeks （n = 6）. All patients had done liver biopsies to determine the severity of liver fibrosis and measured levels of HBV ccc DNA in hepatocytes by real fime-PCR. The relationships between levels ofHBV ccc DNA in hepatocytes and severity of liver fibrosis in group A, and between levels ofHBV ccc DNA in hepatocytes and HBV DNA in serum in both groups were analyzed. Changes ofHBV ccc DNA level in hepatocytes were investigated in group B. Results Both levels of HBV ccc DNA in hepatocytes and HBV DNA in serum were negatively correlated with severity of liver fibrosis, while HBV ccc DNA with more significant relationship （r = -0.465, P = 0.008）. Levels ofHBV ccc DNA in hepatocytes were not correlated with HBV DNA in serum （r = 0.057, P = 0.418）. Levels ofHBV ccc DNA and HBV DNA in patients who received antiviral therapy from group B were significantly decreased compared to the control group （12 patients matched with sex, age and level of HBV DNA from group A）. Total of 3 patients＇ levels ofHBV DNA in serum could not be detected, but HBV ccc DNAstill existed in hepatocytes. Conclusions Levels of HBV ccc DNA in hepatocytes are negatively correlated with severity of liver fibrosis, but levels ofHBV DNA in serum could not reflect the replication of HBV in liver. HBV ccc DNA in hepatocytes could not be cleared completely until antiviml therapy for a long term in patients with CHB.