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慢性乙型肝炎感染患者HBV DNA载量的临床相关性

Clinical relevance of HBV DNA load in patients with chronic hepatitis B infection.

作者信息

Madan K, Batra Y, Jha J K, Kumar Shakti, Kalra Nancy, Paul S B, Singh R, Duttagupta S, Panda S K, Acharya S K

机构信息

Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Trop Gastroenterol. 2008 Apr-Jun;29(2):84-90.

PMID:18972767
Abstract

BACKGROUND

Hepatitis B virus (HBV) DNA detection and quantification are now playing an increasing role in the assessment of disease activity and response to therapy. However, viraemia levels which define various stages of HBV infection have not yet been established.

AIM

To define viraemia levels which describe various stages of chronic hepatitis B virus infection.

METHODS

In a retrospective study, stored sera samples of chronic hepatitis B virus (CHB) infected patients registered at AIIMS liver clinic, from January 1996 to June 2005 were subjected to competitive, quantitative PCR analysis.

RESULTS

The median HBV DNA load was lowest among carriers and highest among patients with chronic hepatitis B [0 (0-8) vs. 7 (0-12) log10 copies/ml, respectively; p<0.05]. As compared to chronic hepatitis patients the DNA load was also lower among cirrhotics [7 (0-12) vs. 4.5 (0-8) log10 copies/ml, respectively; p<0.05] and hepatocellular cancer patients [ 7(0-12) vs. 0 (0-8) log10 copies/ml, respectively; p<0.05]. Patients with carriers had a DNA load which was significantly lower than e antigen negative CHB [0 (0-8) vs. 6 (0-10) log10 copies/ml; p<0.05] or e antigen positive CHB [0 (0-8) vs 8 (0-12) log10 copies/ml; p<0.05]. A threshold of 3.5 log10 copies/ml had sensitivity and specificity of 83% and 58% respectively in differentiating carriers from e antigen negative CHB. There was a strong positive correlation of HBV DNA load with inflammatory grade (R=0.334; p=0.0001), fibrosis stage (R=0.276; p=0.001) and ALT levels (R=0.378; p=0.0001). 82% (9/11) of those who lost e antigen had a decline in HBV DNA levels to <5 log10 copies/ml, whereas only 12.5% (1/8) of those who did not lose e antigen had a decline in DNA load below this level.

CONCLUSIONS

HBV DNA viraemia levels correlate positively with the inflammatory grade, fibrosis stage and ALT levels. Most patients who loose e antigen have a decline in DNA load to below 5 log10 copies/ml. Further prospective studies employing repeated measurements are required to define a threshold to differentiate between HBV carriers and e antigen negative CHB.

摘要

背景

乙肝病毒(HBV)DNA检测及定量在疾病活动评估和治疗反应评估中发挥着越来越重要的作用。然而,尚未确定定义HBV感染各阶段的病毒血症水平。

目的

确定描述慢性乙肝病毒感染各阶段的病毒血症水平。

方法

在一项回顾性研究中,对1996年1月至2005年6月在全印医学科学研究所肝病门诊登记的慢性乙肝病毒(CHB)感染患者的储存血清样本进行竞争性定量PCR分析。

结果

HBV DNA载量中位数在携带者中最低,在慢性乙肝患者中最高[分别为0(0 - 8)对7(0 - 12)log10拷贝/毫升;p<0.05]。与慢性乙肝患者相比,肝硬化患者[分别为7(0 - 12)对4.5(0 - 8)log10拷贝/毫升;p<0.05]和肝细胞癌患者[分别为7(0 - 12)对0(0 - 8)log10拷贝/毫升;p<0.05]的DNA载量也较低。携带者患者的DNA载量显著低于e抗原阴性CHB[0(0 - 8)对6(0 - 10)log10拷贝/毫升;p<0.05]或e抗原阳性CHB[0(0 - 8)对8(0 - 12)log10拷贝/毫升;p<0.05]。3.5 log10拷贝/毫升的阈值在区分携带者与e抗原阴性CHB时,敏感性和特异性分别为83%和58%。HBV DNA载量与炎症分级(R = 0.334;p = 0.0001)、纤维化分期(R = 0.276;p = 0.001)和ALT水平(R = 0.378;p = 0.0001)呈强正相关。82%(9/11)失去e抗原的患者HBV DNA水平降至<5 log10拷贝/毫升,而未失去e抗原的患者中只有12.5%(1/8)的DNA载量降至该水平以下。

结论

HBV DNA病毒血症水平与炎症分级、纤维化分期和ALT水平呈正相关。大多数失去e抗原的患者DNA载量降至5 log10拷贝/毫升以下。需要进一步进行重复测量的前瞻性研究来确定区分HBV携带者和e抗原阴性CHB的阈值。

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