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

Relationship between the serum HBV DNA and the change of the intrahepatic HBV cccDNA levels in antiviral therapy for chronic hepatitis B

作　　者：刘雪艳 商庆华 刘学恩[3] 庄辉[3] 

机构地区：[1]福建广生堂药业股份有限公司,福州350003 [2]山东解放军第八八医院肝病中心 [3]北京大学医学部基础医学院病原生物学系和感染病中心

出　　处：《肝脏》2015年第8期591-596,共6页Chinese Hepatology

基　　金：国家"十二五"传染病重大专项(2013ZX10002004;2012ZX10002003)

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ADV10 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 ADV10 mg/d.The virological,serological and biochemical parameters were measured every 12 weeks during treatment.Liver biopsies were performed in47 patients at baseline and 24 patients at48 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 48 weeks,suggesting serum HBV DNA and HBsAg could not be the alternative for HBV tDNA and cccDNA.

关 键 词：慢性乙型肝炎 阿德福韦酯 乙型肝炎病毒共价闭合环状DNA(HBV cccDNA) 荧光定量PCR 

分 类 号：R512.62[医药卫生—内科学]