慢性乙型肝炎患者抗病毒治疗过程中肝组织HBV cccDNA 变化及与血清学指标的相关性

摘要

目的：观察慢性乙型肝炎（乙肝）患者在阿德福韦酯（ADV）抗病毒治疗过程中肝组织总的乙肝病毒核酸（HBV tDNA）、cccDNA 含量变化及与血清 HBV DNA、HBsAg 的相关性，探讨肝组织 HBV tDNA 和 cccDNA 含量改变在抗病毒治疗中的意义。方法47例慢性乙肝患者口服 ADV 10 mg／d，每隔12周检测病毒学、血清学和生化学等指标。47例基线患者和24例治疗48周患者行肝组织活检及肝组织 HBV tDNA 和 cccDNA 检测。结果47例慢性乙肝患者 ADV治疗48周后，HBV DNA 低于检查下限占36．2％（17／47）；ALT 和 AST 复常率分别为76．6％（36／47）和85．1％（40／47）。比较基线和48周均取肝活检的24例患者，48周时血清和肝组织中 HBV DNA 载量均较基线显著下降（P ＜0．01），血清HBV DNA 下降值大于肝组织 HBV tDNA 和肝组织 HBV cccDNA（分别为3．21 lg 拷贝／ml、1．02 lg 拷贝／细胞和0．76 lg拷贝／细胞）。基线时，24例患者肝组织 HBV tDNA、cccDNA 与血清 HBV DNA 和 HBsAg 呈正相关（P ＜0．01）；但治疗48周时，各指标间无相关性。结论 ADV 治疗慢性乙肝患者可使其肝组织 HBV tDNA、cccDNA 和血清 HBV DNA 水平显著下降，但血清 HBV DNA 下降较肝组织 HBV tDNA、cccDNA 更为显著。%Objective To investigate the correlations between the The serum HBV DNA and the intrahepatic HBV tDNA and cccDNA levels were decreased significantly after 48 weeks intrahepatic HBV tDNA,cccDNA and serum HBV DNA,HBsAg levels in patients with chronic hepatitis B treated with adefovir dipivoxil (ADV).The association between the antiviral response and the changed levels of the intrahepatic HBV tDNA and cccDNA was explored.Methods Forty seven patients with chronic hepatitis B were treated with ADV 10 mg/d.The virological,serological and biochemical parameters were measured every 12 weeks during treatment.Liver biopsies were performed in 47 patients at baseline and 24 patients at 48 weeks.The intrahepatic HBV tDNA and cccDNA levels were quantitated by real-time PCR.Results The sero-negative rate of HBV DNA was 36.2% (17/47),and normalization rates of ALT and AST levels were 76.6%(36/47)and 85.1%(40/47)in 47 patients treated with ADV for 48 weeks.The serum HBV DNA and the intrahepatic HBV tDNA and cccDNA levels were decreased significantly after 48 weeks therapy in 24 patients performed liver biopsies at baseline and 48 weeks. The decreased values of serum HBV DNA,the intrahepatic HBV tDNA and cccDNA were 3.21 log copies/mL,1.02 log copies/cell and 0.76 log copies/cell,respectively (P<0.01).At baseline,the intrahepatic HBV tDNA and cccDNA levels were positively correlated with serum HBV DNA and HBsAg.However,the correlations were not observed after 48 weeks treatment.Conclusion The intrahepatic HBV tDNA、cccDNA and serum HBV DNA levels were decreased significantly after 48 weeks ADV therapy.The correlations between the intrahepatic HBV tDNA,cccDNA and serum HBV DNA, HBsAg levels were observed at baseline but not at 48weeks,suggesting serum HBV DNA and HBsAg could not be the alternative for HBV tDNA and cccDNA.