Serum Hepatitis B Surface Antigen and Hepatitis B e Antigen Titers: Disease Phase Influences Correlation with Viral Load and Intrahepatic Hepatitis B Virus Markers
Serum Hepatitis B Surface Antigen and Hepatitis B e Antigen Titers: Disease Phase Influences Correlation with Viral Load and Intrahepatic Hepatitis B Virus Markers
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DOI：
10.1002/hep.23571
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发表时间：
2010-06-01
期刊：
影响因子：
13.5
通讯作者：
Locarnini, Stephen A.
中科院分区：
文献类型：
--
作者：
Thompson, Alexander J. V.;Nguyen, Tin;Locarnini, Stephen A.
尽管最近提出了B型肝炎表面抗原（HBsAg）和B型肝炎e抗原（HBeAg）滴度的阈值水平来指导慢性B型肝炎（CH B）的治疗，但它们与循环的B型肝炎病毒（HBV）DNA和肝内HBV复制中间体的关系以及新出现的病毒变异的意义仍不清楚。因此，我们检验了HBsAg和HBeAg滴度可能独立于体内病毒复制而变化的假设。总共招募了149名未经治疗的CHB患者（HBeAg阳性，n = 71; HBeAg阴性，n = 78）。HBeAg和HBsAg的定量采用酶免疫法。病毒学特征包括血清HBV DNA载量、HBV基因型、基础核心启动子（BCP）/前核心（PC）序列，以及在一个子集（n = 44）中测量肝内共价闭合环状DNA（cccDNA）和总HBV DNA，以及定量免疫组织化学（IHC）染色HBsAg。HBeAg阳性CHB患者HBsAg与血清HBV DNA、肝内cccDNA及总HBV DNA均呈正相关（r = 0.69，0.71，0.76，P < 0.01）。HBeAg与血清HBV DNA相关（r = 0.60，P < 0.0001），但BCP/PC变异的出现降低了HBeAg滴度，而与病毒复制无关。在HBeAg阴性的CHB中，HBsAg与血清HBV DNA相关性较差（r = 0.28，P = 0.01），与肝内cccDNA和总HBV DNA均无相关性。肝细胞HBsAg的定量IHC证实仅在HBeAg阳性患者中与病毒复制相关。结论：定量HBsAg滴度与血清和肝内HBV复制标志物之间的相关性在HBeAg阳性和HBeAg阴性的CHB患者之间存在差异。HBeAg滴度的下降可能与病毒复制无关，因为HBeAg缺陷型变异在HBeAg血清转换之前出现。这些发现为病毒的发病机制提供了新的见解，并对定量血清学作为临床生物标志物的应用具有实际意义。（肝脏学2010;51：1933-1944）
Although threshold levels for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) titers have recently been proposed to guide therapy for chronic hepatitis B (CHB), their relationship to circulating hepatitis B virus (HBV) DNA and intrahepatic HBV replicative intermediates, and the significance of emerging viral variants, remains unclear. We therefore tested the hypothesis that HBsAg and HBeAg titers may vary independently of viral replication in vivo. In all, 149 treatment-naive CHB patients were recruited (HBeAg-positive, n = 71; HBeAg-negative, n = 78). Quantification of HBeAg and HBsAg was performed by enzyme immunoassay. Virological characterization included serum HBV DNA load, HBV genotype, basal core promoter (BCP)/precore (PC) sequence, and, in a subset (n = 44), measurement of intrahepatic covalently closed circular DNA (cccDNA) and total HBV DNA, as well as quantitative immunohistochemical (IHC) staining for HBsAg. In HBeAg-positive CHB, HBsAg was positively correlated with serum HBV DNA and intrahepatic cccDNA and total HBV DNA (r = 0.69, 0.71, 0.76, P < 0.01). HBeAg correlated with serum HBV DNA (r = 0.60, P < 0.0001), although emerging BCP/PC variants reduced HBeAg titer independent of viral replication. In HBeAg-negative CHB, HBsAg correlated poorly with serum HBV DNA (r = 0.28, P = 0.01) and did not correlate with intrahepatic cccDNA nor total HBV DNA. Quantitative IHC for hepatocyte HBsAg confirmed a relationship with viral replication only in HBeAg-positive patients. Conclusion: The correlation between quantitative HBsAg titer and serum and intrahepatic markers of HBV replication differs between patients with HBeAg-positive and HBeAg-negative CHB. HBeAg titers may fall independent of viral replication as HBeAg-defective variants emerge prior to HBeAg seroconversion. These findings provide new insights into viral pathogenesis and have practical implications for the use of quantitative serology as a clinical biomarker. (HEPATOLOGY 2010;51:1933-1944)